Silvia C Formenti, M.D.

Comparison of three-dimensional versus intensity-modulated radiotherapy techniques to treat breast and axillary level III and supraclavicular nodes in a prone versus supine position
Sethi RA; No HS; Jozsef G; Ko JP; Formenti SC
2012 Jan;102(1):74-81, Radiotherapy & oncology
BACKGROUND AND PURPOSE: To determine the optimal method of targeting breast and regional nodes in selected breast cancer patients after axillary dissection, we compared the results of IMRT versus no IMRT, and CT-informed versus clinically-placed fields, in supine and prone positions. MATERIALS AND METHODS: Twelve consecutive breast cancer patients simulated both prone and supine provided the images for this study. Four techniques were used to target breast, level III axilla, and supraclavicular fossa in either position: a traditional three-field three-dimensional conformal radiotherapy (3DCRT) plan, a four-field 3DCRT plan using a posterior axillary boost field, and two techniques using a CT-informed target volume consisting of an optimized 3DCRT plan (CT-planned 3D) and an intensity-modulated radiotherapy (IMRT) plan. The prescribed dose was 50Gy in 25 fractions. RESULTS: CT-planned 3D and IMRT techniques improved nodal PTV coverage. Supine, mean nodal PTV V50 was 50% (3-field), 59% (4-field), 92% (CT-planned 3D), and 94% (IMRT). Prone, V50 was 29% (3-field), 42% (4-field), 97% (CT-planned 3D), and 95% (IMRT). Prone positioning, compared to supine, and IMRT technique, compared to 3D, lowered ipsilateral lung V20. CONCLUSIONS: Traditional 3DCRT plans provide inadequate nodal coverage. Prone IMRT technique resulted in optimal target coverage and reduced ipsilateral lung V20
— id: 145493, year: 2012, vol: 102, page: 74, stat: Journal Article,

Low-dose radiation knowledge worth the cost
Barcellos-Hoff, Mary Helen; Brenner, David J; Brooks, Antone L; Formenti, Silvia; Hlatky, Lyn; Locke, Paul A; Shore, Roy; Tenforde, Thomas; Travis, Elizabeth L; Williams, Jacqueline
2011 Apr 15;332(6027):305-306, Science
— id: 140490, year: 2011, vol: 332, page: 305, stat: Journal Article,

Increased radiosensitivity in vivo following inhibition of transforming growth factor beta in murine model of triple negative breast cancer
Bouquet S.F.; Pilones K.; Demaria S.; DeWyngaert K.J.; Lonning S.; Formenti S.; Barcellos-Hoff M.
2011 ;81(2 SUPPL 1):S714-S715, International journal of radiation oncology biology physics
Purpose/Objective(s): Ionizing radiation triggers activation of transforming growth factor beta1 (TGFbeta), a growth factor that promotes invasion and suppresses immune function. Either genetic or pharmaceutical TGFbeta inhibition prior to IR also inhibits the DNA damage response (DDR) in epithelial cells via blockade of ATM kinase activity (Cancer Res 62:5627, 2002; Cancer Res 66:10861, 2006). Moreover, transient TGFbeta inhibition increases the radiosensitivity of epithelial cancer cells (Bouquet et al. submitted). The current studies test the optimal combination of TGFbeta inhibition using neutralizing antibodies with radiotherapy (RT) in a model of triple negative breast cancer. Materials/Methods: The 4T1 murine mammary tumor model is highly metastatic when grown as subcutaneous tumors. 4T1 cells were injected s.c. in the flank of syngeneic Balb/c mice and about 13 days after implantation approximately 100 mm3 tumors were locally irradiated. An anti-TGFb murine monoclonal antibody, 1D11, was administered i.p. before irradiation. Mice were randomly assigned to four groups receiving control isotype monoclonal antibody, 1D11, RT (8 Gy) and isotype control antibody, or RT and 1D11. Tumor growth, DDR, lymphocyte infiltration, lung metastases and/or survival were evaluated. Results: TGFb TGFb inhibition in vivo reduced DDR as evidenced by gH2AX foci in irradiated tumors. A single injection of 1D11 (5 mg/kg) 24 hr before RT resulted in greater tumor growth delay compared to RT and control antibody (p<0.05). Furthermore, chronic treatment with a higher 1D11 dose (10 mg/kg or 50 mg/kg) in the context of fractionated RT significantly reduced tumor growth rate, decreased visible lung metastases and increased survival (p<0.05). Notably this RT+1D11 protocol increased tumor infiltration of CD8, but not CD4, T lymphocytes, which resulted in a significantly enhanced ratio of CD8+NKG2D+ effector cells to CD4+ T cells in the tumor, suggesting that TGFb inhibition also alters the immunological environment in irradiated tumors. Conclusions: Increased radiosensitivity of 4T1 tumor cells in vitro and in vivo supports the use of TGFb inhibitors as means to increase the response to RT. Moreover, an additional benefit may be that TGFb inhibition promotes an anti-tumor immune response to RT
— id: 150891, year: 2011, vol: 81, page: S714, stat: Journal Article,

TGFbeta1 Inhibition Increases the Radiosensitivity of Breast Cancer Cells In Vitro and Promotes Tumor Control by Radiation In Vivo
Bouquet, Fanny; Pal, Anupama; Pilones, Karsten A; Demaria, Sandra; Hann, Byron; Akhurst, Rosemary J; Babb, Jim S; Lonning, Scott M; Dewyngaert, J Keith; Formenti, Silvia C; Barcellos-Hoff, Mary Helen
2011 Nov 1;17(21):6754-6765, Clinical cancer research
PURPOSE: To determine whether inhibition of TGFbeta signaling prior to irradiation sensitizes human and murine cancer cells in vitro and in vivo. EXPERIMENTAL DESIGN: TGFbeta-mediated growth and Smad phosphorylation of MCF7, Hs578T, MDA-MB-231, and T47D human breast cancer cell lines were examined and correlated with clonogenic survival following graded radiation doses with and without pretreatment with LY364947, a small molecule inhibitor of the TGFbeta type I receptor kinase. The DNA damage response was assessed in irradiated MDA-MB-231 cells pretreated with LY364947 in vitro and LY2109761, a pharmacokinetically stable inhibitor of TGFbeta signaling, in vivo. The in vitro response of a syngeneic murine tumor, 4T1, was tested using a TGFbeta neutralizing antibody, 1D11, with single or fractionated radiation doses in vivo. RESULTS: Human breast cancer cell lines pretreated with TGFbeta small molecule inhibitor were radiosensitized, irrespective of sensitivity to TGFbeta growth inhibition. Consistent with increased clonogenic cell death, radiation-induced phosphorylation of H2AX and p53 was significantly reduced in MDA-MB-231 triple-negative breast cancer cells when pretreated in vitro or in vivo with a TGFbeta type I receptor kinase inhibitor. Moreover, TGFbeta neutralizing antibodies increased radiation sensitivity, blocked gammaH2AX foci formation, and significantly increased tumor growth delay in 4T1 murine mammary tumors in response to single and fractionated radiation exposures. CONCLUSION: These results show that TGFbeta inhibition prior to radiation attenuated DNA damage responses, increased clonogenic cell death, and promoted tumor growth delay, and thus may be an effective adjunct in cancer radiotherapy. Clin Cancer Res; 17(21); 6754-65. (c)2011 AACR
— id: 140531, year: 2011, vol: 17, page: 6754, stat: Journal Article,

The role of health system factors in delaying final diagnosis and treatment of breast cancer in Mexico City, Mexico
Bright, Kristin; Barghash, Maya; Donach, Martin; de la Barrera, Marcos Gutierrez; Schneider, Robert J; Formenti, Silvia C
2011 Apr;20 Suppl 2:S54-S59, Breast
In Mexico, breast cancer is the leading cancer-related death among women and most cases are diagnosed at advanced stages (50-60%). We hypothesized health system factors could be partly responsible for this delay and performed a prospective review of 166 new breast cases at a major public hospital in Mexico City. Our analysis confirmed the prevalence of locally advanced and metastatic disease (47% of patients). A subset analysis of 32 women with confirmed stage I-IIIC breast cancer found an average time interval of 1.8 months from symptom onset to first primary care consultation (PCC), with an additional 6.6 months from first PCC to confirmed diagnosis, and 0.6 months from diagnosis to treatment initiation. Patients underwent an average of 7.9 clinic visits before confirmed diagnosis. Findings suggest that protracted referral time from primary to specialty care accounts for the bulk of delay, with earlier stage patients experiencing longer delays. These findings reveal a critical need for further study and exploration of interventions
— id: 130301, year: 2011, vol: 20 Suppl 2, page: S54, stat: Journal Article,

Breast cancer overview
DeWyngaert JK; Jozsef G; Lymberis S; Becker S; Formenti SC
Image-guided radiation therapy : a clinical perspective Shelton, Conn. : People's Medical Pub. House-USA, 2011,
— id: 5979, year: 2011, vol: , page: 285, stat: Chapter,

Surgical outcomes of 63 patients from an international trial of preoperative concurrent paclitaxel- Radiation in locally advanced breast cancer
Dhage S.; Axelrod D.; Guth A.; Vijaykumar D.K.; Apffelstaedt J.; Formenti S.
2011 ;18:S166-S166, Annals of surgical oncology
Objective: Locally advanced breast cancer (LABC) is the most common presentation of breast cancer worldwide. In the United States, neoadjuvant therapy has become the standard of care for LABC. Recently, Adams et al reported a 34% pathologic response rate among 105 patients with LABC treated with taxanebased, preoperative chemo-radiation: 5-year DFS and OS results were comparable to those of much more aggressive chemotherapy regimens in the neoadjuvant setting. As is reported for patients treated by neoadjuvant chemotherapy, the achievement of a pathological response to chemo-radiation reflected better DFS and OS. Importantly, a pathological response occurred in 54% of patients with hormone-negative tumors. Since this approach is simple and cost-effective, it has attracted interest from several international centers. We report the surgical outcomes after taxane-radiation in 63 LABC patients treated in a multiinstitutional clinical trial in India, South Africa, and the United States. Methods: Women with LABC (stages IIB-IIIC), ECOG performance status of 0 to 1, were eligible. Patients were treated with paclitaxel (30 mg/m(2) intravenously twice a week) for 6-12 weeks. Daily radiotherapy was delivered to breast, axillary, and supraclavicular lymph nodes during weeks 2-7 of paclitaxel treatment, at 1.8 Gy per fraction to a total dose of 45 Gy with a tumor boost of 14 Gy at 2 Gy/fraction. Seventeen of 63 patients received four cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 prior to the paclitaxel -RT regimen. Mastectomy or lumpectomy, as decided by each surgeon, was performed 4 weeks after completion of preoperative therapy or upon recovery of chemoradiationinduced dermatitis. All patients had a level I/II axillary lymph node dissection. Postoperatively, patients who responded to paclitaxel and RT received four cycles of doxorubicin/paclitaxel, whereas patients who did not respond received doxorubicin/cytoxan. Surgical complications were recorded. Results: Forty-three patients underwent modified radical mastectomyand 20 underwent lumpectomy. Of mastectomy patients, 17 (39.5%) underwent immediate breast reconstruction: free flap reconstruction (8), pedicle flaps (3), advancement flaps(2), tissue expander placement (2), and major chest wall and sternum reconstruction (1). Of lumpectomy patients, five (25%) had further surgery for positive margins; a second lumpectomy (3), and a mastectomy (2). All revealed residual disease and negative margins were achieved. Twenty-one patients had at least 1 complication of whom 17 were treated as outpatients. Eleven (17.4%) had a recurrent seroma, 8 (12.7%) had delayed healing, and 7 (11.1%) developed a postoperative infection. Of the 17 who underwent reconstruction, 3 (17.6%) developed flap necrosis, requiring surgical debridement. The degree of acute chemo-radiation dermatitis was analyzed to explore correlation with the surgical complications. Dermatitis was grade 1 in 21 patients, grade 2 in 29 patients, grade 3 in 11 patients, and 2 had none. The grade of dermatitis did not correlate with risk of complications. Conclusions: Preoperative paclitaxel with radiotherapy is relatively well tolerated. Risk of complication is similar to that reported in the literature for patients treated with neoadjuvant therapy. The highest morbidity was associated with immediate free flap reconstruction. Delayed reconstruction may be advisable for patients treated with neoadjuvant chemo-radiation. (Table presented)
— id: 137914, year: 2011, vol: 18, page: S166, stat: Journal Article,

Abscopal immune response linked to radiotherapy
Formenti S.
2011 ;99:S48-S48, Radiotherapy & oncology
Over the past ten years we have developed a clinical translational program based on the rationale of immunizing patients against their own tumor by concomitantly: 1) removing existing breaks in their immune system and, 2) harnessing local RT-induced physical and biological perturbations at the irradiated tumor site, to achieve the successful conversion of the original tumor into an immunogenic hub (1, 2). To mimic the common clinical setting of established, metastatic cancer, we have employed as a model the poorly immunogenic 4T1 mouse mammary carcinoma. After s.c. inoculation 4T1 cells grow to form a highly invasive primary tumor that early on sheds spontaneous metastases to the lungs, and other organs (3). Mice usually die of metastatic disease to the lungs. 9H10 mAb against CTLA-4 releases a negative regulator of T cell activation. We demonstrated the effects of combining RT with CTLA-4 blockade given two weeks after implantation in mice, when primary tumors are palpable and metastatic cells have already spread systemically (4). Whereas single modality treatment was ineffective, RT and CTLA-4 blockade elicited CD8 T-cell-dependent antitumor immunity. The immune response effectively inhibited the growth of spontaneous lung metastases prolonging the survival time of animals. However, cure was rare, and most mice eventually succumbed to their disease (4). In the same models we found that RT enhanced the secretion by cancer cells of CXCL16, a chemokine that binds to CXCR6 on Th1 and activated CD8 effector T cells, and mediates their recruitment to sites of inflammation. CXCR6-deficient mice showed reduced infiltration of tumors by activated CD8 T cells and impaired tumor regression after RT and 9H10 (5). The contribution of invariant natural killer T (iNKT) cells, a subset with unique regulatory functions, in the response to RT and CTLA-4 blockade was then investigated. Growth of 4T1 primary tumors and lung metastases was compared in wild type (WT) and iNKT cells-deficient (iNKT/) mice, resulting in long-term survival, and resistance to a challenge with 4T1 cells (6). In preparation to a clinical translation of these findings we hypothesized that the type of dose fractionation regimen determines the ability of radiotherapy to synergize with antiCTLA-4 antibody. Using TSA mouse breast carcinoma and MCA38 mouse colon carcinoma models, cells were injected s.c. into syngeneic mice at two separate sites, defined as a primary site that was irradiated and a secondary site outside the radiotherapy field. Mice were randomly assigned to eight groups receiving no radiotherapy or three distinct regimens of radiotherapy (20 Gy in a single fraction, 8 Gy in 3 fractions, or 6 Gy in five 5 fractions, on consecutive days), +/- 9H10. In neither of the two models tested, treatment with 9H10 alone had detectable effect. Each of the radiotherapy regimens caused comparable growth delay of the primary tumors but had no effect on the secondary tumors, outside the radiation field. Conversely, 9H10 with either fractionated RT regimens (but not with single dose RT) achieved enhanced tumor response at the primary and secondary site (P < 0.0001). The frequency of CD8+ T cells showing tumor-specific IFNgamma production was proportional to the inhibition of the secondary tumor (7). The findings on dose and fractionation were translated to a preclinical experiment, that tests the combination of radiotherapy and fresolimumab, a monoclonal antibody against TGFbeta. A clinical trial to test this combination in metastatic breast cancer is ongoing, aiming at detecting abscopal responses in metastases outside the radiation field
— id: 135596, year: 2011, vol: 99, page: S48, stat: Journal Article,

Role of T-lymphocytes for tumour response to radiotherapy
Formenti S.; Encouse G.; Adams S.; Pilones K.; Grazia Ruocco M.; Dustin M.; Demaria S.
2011 ;47:S11-S11, European journal of cancer
Over the past ten years we have developed a clinical translational program based on the rationale of immunizing patients against their own tumour by concomitantly: 1) removing existing 'breaks' in their immune system and 2) harnessing local ionizing radiation (IR) to induce physical and biological perturbations at the irradiated tumour site, to achieve the successful conversion of the original tumour into an immunogenic hub (Formenti, Lancet Oncology 2009). Preclinical investigations have shed some light on the specific role of T cells in these processes. For instance, in the 4T1 syngeneic murine model of metastatic breast cancer targeting regulatory receptors or cells (Treg) by anti-CTLA-4 and anti-CD25 antibodies, respectively, synergized with IR and reduced the number of metastases to the lung (an abscopal effect, defined as a significant growth inhibition of the tumour outside the irradiated field) in a CD8+ T cells dependent way. In the same model IR increased the migration of CD8 CXCR6 activated T cells to tumours. This effect was mediated by IRenhanced secretion by cancer cells of CXCL16, a chemokine that binds to CXCR6 on Th1 and activated CD8 effector T cells. CXCR6-deficient mice showed reduced infiltration of tumours by activated CD8+ T cells and impaired tumour regression following treatment with local IR + CTLA-4 blockade. Interestingly, an abscopal effect, occurred only in mice treated with the combination of 9H10 and fractionated radiotherapy, but not when a single dose of 20 Gy was administered (P < 0.01), as reflected by the frequency of CD8+ T cells showing tumour-specific IFN-gamma production. The contribution of invariant natural killer T (iNKT) cells, a subset with unique regulatory functions, in the response to IR and CTLA-4 blockade was also studied. Growth of 4T1 primary tumours and lung metastases was compared in wild type (WT) and iNKT cells-deficient (iNKT-/-) mice. The response to IR+CTLA-4 blockade was markedly enhanced in the absence of iNKT cells: 50% of iNKT-/- compared to none of the WT mice had complete tumour regression, long-term survival, and resistance to a challenge with 4T1 cells. Finally, intravital microscopy demonstrated that while both IR and CTLA-4 blockade given as monotherapy enhanced the motility of activated CD8 T cells infiltrating 4T1 tumours, IR with anti-CTLA-4 increased the arrest of T cells in contact with tumour cells. The latter required interaction of NKG2D on CD8+ T cells with its ligand retinoic acid early inducible-1 (Rae-1) on the tumour cells, which was up-regulated by IR. Blocking NKG2D-Rae-1 interactions increased markedly the motility of anti-CTLA-4 treated T cells within irradiated tumours inhibiting their contact with tumour cells, and abrogated immune-mediated tumour rejection, suggesting a critical role of radiation-induced NKG2D ligands for the antitumour effects of anti-CTLA-4 in the setting of a poorly immunogenic tumour
— id: 138729, year: 2011, vol: 47, page: S11, stat: Journal Article,

Re: Long-term Outcomes of Invasive Ipsilateral Breast Tumor Recurrences After Lumpectomy in NSABP B-17 and B-24 Randomized Clinical Trials for DCIS
Formenti, Silvia C; Arslan, Alan A; Pike, Malcolm C
2011 Nov 16;103(22):1723-1723, Journal of the National Cancer Institute
— id: 141699, year: 2011, vol: 103, page: 1723, stat: Journal Article,

Prone Hypofractionated Whole-Breast Radiotherapy Without a Boost to the Tumor Bed: Comparable Toxicity of IMRT Versus a 3D Conformal Technique
Hardee ME; Raza S; Becker SJ; Jozsef G; Lymberis SC; Hochman T; Goldberg JD; Dewyngaert KJ; Formenti SC
2011 Mar 1;82(3):e415-e423, International journal of radiation oncology biology physics
PURPOSE: We report a comparison of the dosimetry and toxicity of three-dimensional conformal radiotherapy (3D-CRT) vs. intensity-modulated radiotherapy (IMRT) among patients treated in the prone position with the same fractionation and target of the hypofractionation arm of the Canadian/Whelan trial. METHODS AND MATERIALS: An institutional review board-approved protocol identified a consecutive series of early-stage breast cancer patients treated according to the Canadian hypofractionation regimen but in the prone position. Patients underwent IMRT treatment planning and treatment if the insurance carrier approved reimbursement for IMRT; in case of refusal, a 3D-CRT plan was used. A comparison of the dosimetric and toxicity outcomes during the acute, subacute, and long-term follow-up of the two treatment groups is reported. RESULTS: We included 97 consecutive patients with 100 treatment plans in this study (3 patients with bilateral breast cancer); 40 patients were treated with 3D-CRT and 57 with IMRT. IMRT significantly reduced the maximum dose (Dmax median, 109.96% for 3D-CRT vs. 107.28% for IMRT; p < 0.0001, Wilcoxon test) and improved median dose homogeneity (median, 1.15 for 3D-CRT vs. 1.05 for IMRT; p < 0.0001, Wilcoxon test) when compared with 3D-CRT. Acute toxicity consisted primarily of Grade 1 to 2 dermatitis and occurred in 92% of patients. Grade 2 dermatitis occurred in 13% of patients in the 3D-CRT group and 2% in the IMRT group. IMRT moderately decreased rates of acute pruritus (p = 0.03, chi-square test) and Grade 2 to 3 subacute hyperpigmentation (p = 0.01, Fisher exact test). With a minimum of 6 months' follow-up, the treatment was similarly well tolerated in either group, including among women with large breast volumes. CONCLUSION: Hypofractionated breast radiotherapy is well tolerated when treating patients in the prone position, even among those with large breast volumes. Breast IMRT significantly improves dosimetry but yields only a modest but confirmed benefit in terms of toxicities. If a concurrent boost to the tumor bed is not required, a conformal 3D-CRT approach can adequately deliver prone whole-breast hypofractionation radiotherapy
— id: 145492, year: 2011, vol: 82, page: e415, stat: Journal Article,

Prospective study of cone-beam computed tomography image-guided radiotherapy for prone accelerated partial breast irradiation
Jozsef, Gabor; Dewyngaert, J Keith; Becker, Stewart J; Lymberis, Stella; Formenti, Silvia C
2011 Oct 1;81(2):568-574, International journal of radiation oncology biology physics
PURPOSE: To report setup variations during prone accelerated partial breast irradiation (APBI). METHODS: New York University (NYU) 07-582 is an institutional review board-approved protocol of cone-beam computed tomography (CBCT) to deliver image-guided ABPI in the prone position. Eligible are postmenopausal women with pT1 breast cancer excised with negative margins and no nodal involvement. A total dose of 30 Gy in five daily fractions of 6 Gy are delivered to the planning target volume (the tumor cavity with 1.5-cm margin) by image-guided radiotherapy. Patients are set up prone, on a dedicated mattress, used for both simulation and treatment. After positioning with skin marks and lasers, CBCTs are performed and the images are registered to the planning CT. The resulting shifts (setup corrections) are recorded in the three principal directions and applied. Portal images are taken for verification. If they differ from the planning digital reconstructed radiographs, the patient is reset, and a new CBCT is taken. RESULTS: 70 consecutive patients have undergone a total of 343 CBCTs: 7 patients had four of five planned CBCTs performed. Seven CBCTs (2%) required to be repeated because of misalignment in the comparison between portal and digital reconstructed radiograph image after the first CBCT. The mean shifts and standard deviations in the anterior-posterior (AP), superior-inferior (SI), and medial-lateral (ML) directions were -0.19 (0.54), -0.02 (0.33), and -0.02 (0.43) cm, respectively. The average root mean squares of the daily shifts were 0.50 (0.28), 0.29 (0.17), and 0.38 (0.20). A conservative margin formula resulted in a recommended margin of 1.26, 0.73, 0.96 cm in the AP, SI, and ML directions. CONCLUSION: CBCTs confirmed that the NYU prone APBI setup and treatment technique are reproducible, with interfraction variation comparable to those reported for supine setup. The currently applied margin (1.5 cm) adequately compensates for the setup variation detected
— id: 136994, year: 2011, vol: 81, page: 568, stat: Journal Article,

Loss of p27KIP1 Expression in Fully-staged Node-negative Breast Cancer: Association with Lack of Hormone Receptors in T1a/b, but not T1c Infiltrative Ductal Carcinoma
Mirchandani, Deepu; Roses, Daniel F; Inghirami, Giorgio; Zeleniuch-Jacquotte, Anne; Cangiarella, Joan; Guth, Amber; Safyan, Rachael Ann; Formenti, Silvia C; Pagano, Michele; Muggia, Franco
2011 Dec;31(12):4401-4405, Anticancer research
Nuclear expression of the cell cycle inhibitor p27(KIP1) is reduced in a variety of human malignancies, including breast cancer. Loss of nuclear p27(KIP1) during tumor progression, documented by immunohistochemistry (IHC), has been studied for its potential prognostic implication. We examined by IHC the association between nuclear p27(KIP1) expression and hormone receptor status in T1N0M0 breast cancer. PATIENTS AND METHODS: The correlation between nuclear p27(KIP1) expression and estrogen (ER) and progesterone (PR) hormone receptor status was analyzed in 122 human T1N0M0 (68 T1a/b, 54 T1c) breast cancer specimens. All patients were staged as N0 by axillary node dissection. RESULTS: A statistically significant reduction in p27(KIP1) expression was observed as tumor size increased from T1a/b (7%) to T1c (22%). The proportion of tumors with low nuclear p27(KIP1) expression was higher in the ER-negative/PR-negative group compared to the ER-positive/PR-positive group, but this difference was only statistically significant in the T1a/b subgroup (p=0.0007). CONCLUSION: Further investigations into causes of p27(KIP1) deregulation and their relationship to hormone receptor expression in T1N0M0 breast ductal carcinomas are warranted. Such studies may help identify prognostic, as well as predictive, markers of therapy resistance
— id: 149934, year: 2011, vol: 31, page: 4401, stat: Journal Article,

Hereditary breast cancer: clinical features and risk reduction strategies
Paradiso, A; Formenti, S
2011 Jan;22 Suppl 1:i31-i36, Annals of oncology
Risk-reduction interventions for BRCA-related breast cancer are relevant not only for clinical decisions in breast cancer patients but also for healthy subjects who are potential candidates to undergo similar interventions. The literature on the impact of different surgical options and adjuvant systemic approaches aimed towards risk reduction for ipsilateral and contralateral breast cancer recurrences is briefly reviewed. Breast-conserving surgery is associated with a higher probability of local recurrence, but is counterbalanced by effectiveness of chemotherapy in reducing this risk. Consistent support for the hypothesis that antiestrogens are effective in reducing contralateral breast cancer risks is available from the literature. On the other hand, data on chemoprevention approaches for healthy subjects are too preliminary to draw any conclusions. Studies including conventional and newer hormonal drugs are needed to demonstrate the benefit of chemoprevention approaches. These may also deepen our knowledge on possible differences in the likelihood of clinical benefit to be expected among BRCA1- and BRCA2-altered tumours
— id: 134114, year: 2011, vol: 22 Suppl 1, page: i31, stat: Journal Article,

Intravoxel incoherent motion imaging of tumor microenvironment in locally advanced breast cancer
Sigmund, E E; Cho, G Y; Kim, S; Finn, M; Moccaldi, M; Jensen, J H; Sodickson, D K; Goldberg, J D; Formenti, S; Moy, L
2011 May;65(5):1437-1447, Magnetic resonance in medicine
Diffusion-weighted imaging plays important roles in cancer diagnosis, monitoring, and treatment. Although most applications measure restricted diffusion by tumor cellularity, diffusion-weighted imaging is also sensitive to vascularity through the intravoxel incoherent motion effect. Hypervascularity can confound apparent diffusion coefficient measurements in breast cancer. We acquired multiple b-value diffusion-weighted imaging at 3 T in a cohort of breast cancer patients and performed biexponential intravoxel incoherent motion analysis to extract tissue diffusivity (D(t) ), perfusion fraction (f(p) ), and pseudodiffusivity (D(p) ). Results indicated significant differences between normal fibroglandular tissue and malignant lesions in apparent diffusion coefficient mean (+/-standard deviation) values (2.44 +/- 0.30 vs. 1.34 +/- 0.39 mum(2) /msec, P < 0.01) and D(t) (2.36 +/- 0.38 vs. 1.15 +/- 0.35 mum(2) /msec, P < 0.01). Lesion diffusion-weighted imaging signals demonstrated biexponential character in comparison to monoexponential normal tissue. There is some differentiation of lesion subtypes (invasive ductal carcinoma vs. other malignant lesions) with f(p) (10.5 +/- 5.0% vs. 6.9 +/- 2.9%, P = 0.06), but less so with D(t) (1.14 +/- 0.32 mum(2) /msec vs. 1.18 +/- 0.52 mum(2) /msec, P = 0.88) and D(p) (14.9 +/- 11.4 mum(2) /msec vs. 16.1 +/- 5.7 mum(2) /msec, P = 0.75). Comparison of intravoxel incoherent motion biomarkers with contrast enhancement suggests moderate correlations. These results suggest the potential of intravoxel incoherent motion vascular and cellular biomarkers for initial grading, progression monitoring, or treatment assessment of breast tumors. Magn Reson Med, 2011. (c) 2011 Wiley-Liss, Inc
— id: 131795, year: 2011, vol: 65, page: 1437, stat: Journal Article,

Preoperative concurrent paclitaxel-radiation in locally advanced breast cancer: pathologic response correlates with five-year overall survival
Adams, Sylvia; Chakravarthy, A Bapsi; Donach, Martin; Spicer, Darcy; Lymberis, Stella; Singh, Baljit; Bauer, Joshua A; Hochman, Tsivia; Goldberg, Judith D; Muggia, Franco; Schneider, Robert J; Pietenpol, Jennifer A; Formenti, Silvia C
2010 Dec;124(3):723-732, Breast cancer research & treatment
We have previously demonstrated high pathologic response rates after neoadjuvant concurrent chemoradiation in patients with locally advanced breast cancer (LABC). We now report disease-free survival (DFS) and overall survival (OS) in the context of pathologic response. 105 LABC patients (White 46%, Non-White 54%) were treated with paclitaxel (30 mg/m(2) intravenously twice a week) for 10-12 weeks. Daily radiotherapy was delivered to breast, axillary, and supraclavicular lymph nodes during weeks 2-7 of paclitaxel treatment, at 1.8 Gy per fraction to a total dose of 45 Gy with a tumor boost of 14 Gy at 2 Gy/fraction. Pathological complete response (pCR) was defined as the absence of invasive cancer in breast and lymph nodes and pathological partial response (pPR) as the persistence of <10 microscopic foci of invasive carcinoma in breast or lymph nodes. Pathologic response (pCR and pPR) after neoadjuvant chemoradiation was achieved in 36/105 patients (34%) and was associated with significantly better DFS and OS. Pathological responders had a lower risk of recurrence or death (HR = 0.35, P = 0.01) and a longer OS (HR = 4.27, P = 0.01) compared with non-responders. Median DFS and OS were 57 and 84 months for non-responders, respectively, and have not yet been reached for responders. Importantly, pathologic response was achieved in 54% of patients with HR negative tumors (26/48). In conclusion, pathologic response to concurrent paclitaxel-radiation translated into superior DFS and OS. Half of the patients with HR negative tumors achieved a pathologic response
— id: 114178, year: 2010, vol: 124, page: 723, stat: Journal Article,

Multiplicity of Favorable Effects after Transforming Growth Factor-beta Inhibition in 4T1 Murine Mammary Tumors: Clinical Implications
Barcellos-Hoff, M. H.; Bouquet, S. F.; Pilones, K. A.; Demaria, S.; Formenti, S. C.
2010 OCT 13 ;78(3):S648-S648, International journal of radiation oncology biology physics
— id: 114022, year: 2010, vol: 78, page: S648, stat: Journal Article,

Identification of markers of taxane sensitivity using proteomic and genomic analyses of breast tumors from patients receiving neoadjuvant paclitaxel and radiation
Bauer, Joshua A; Chakravarthy, A Bapsi; Rosenbluth, Jennifer M; Mi, Deming; Seeley, Erin H; De Matos Granja-Ingram, Nara; Olivares, Maria G; Kelley, Mark C; Mayer, Ingrid A; Meszoely, Ingrid M; Means-Powell, Julie A; Johnson, Kimberly N; Tsai, Chiaojung Jillian; Ayers, Gregory D; Sanders, Melinda E; Schneider, Robert J; Formenti, Silvia C; Caprioli, Richard M; Pietenpol, Jennifer A
2010 Jan 15;16(2):681-690, Clinical cancer research
PURPOSE: To identify molecular markers of pathologic response to neoadjuvant paclitaxel/radiation treatment, protein and gene expression profiling were done on pretreatment biopsies. EXPERIMENTAL DESIGN: Patients with high-risk, operable breast cancer were treated with three cycles of paclitaxel followed by concurrent paclitaxel/radiation. Tumor tissue from pretreatment biopsies was obtained from 19 of the 38 patients enrolled in the study. Protein and gene expression profiling were done on serial sections of the biopsies from patients that achieved a pathologic complete response (pCR) and compared to those with residual disease, non-pCR (NR). RESULTS: Proteomic and validation immunohistochemical analyses revealed that alpha-defensins (DEFA) were overexpressed in tumors from patients with a pCR. Gene expression analysis revealed that MAP2, a microtubule-associated protein, had significantly higher levels of expression in patients achieving a pCR. Elevation of MAP2 in breast cancer cell lines led to increased paclitaxel sensitivity. Furthermore, expression of genes that are associated with the basal-like, triple-negative phenotype were enriched in tumors from patients with a pCR. Analysis of a larger panel of tumors from patients receiving presurgical taxane-based treatment showed that DEFA and MAP2 expression as well as histologic features of inflammation were all statistically associated with response to therapy at the time of surgery. CONCLUSION: We show the utility of molecular profiling of pretreatment biopsies to discover markers of response. Our results suggest the potential use of immune signaling molecules such as DEFA as well as MAP2, a microtubule-associated protein, as tumor markers that associate with response to neoadjuvant taxane-based therapy
— id: 109144, year: 2010, vol: 16, page: 681, stat: Journal Article,

Depletion of T Cells Potentiates Radiation-induced Acute Pneumonitis
Cheng, S. K.; Formenti, S.; Munger, J.
2010 OCT 13 ;78(3):S37-S38, International journal of radiation oncology biology physics
— id: 114014, year: 2010, vol: 78, page: S37, stat: Journal Article,

Inflammatory Breast Cancer Radio-resistance and its Cancer Stem Cell Population are Oppositely Controlled by Translation Factor elF4G
Connolly, E. P.; Silvera, D.; Badura, M. L.; Braunstein, S. E.; Formenti, S. C.; Schneider, R. J.
2010 OCT 13 ;78(3):S221-S221, International journal of radiation oncology biology physics
— id: 114017, year: 2010, vol: 78, page: S221, stat: Journal Article,

Five-year Results of Prone Accelerated Partial Breast Irradiation: NYU 00-23
Formenti, S.
2010 OCT 13 ;78(3):S206-S206, International journal of radiation oncology biology physics
— id: 114015, year: 2010, vol: 78, page: S206, stat: Journal Article,

More radiotherapy for radiation-induced second malignancies?
Formenti, Silvia
2010 Dec;124(3):851-852, Breast cancer research & treatment
— id: 114165, year: 2010, vol: 124, page: 851, stat: Journal Article,

Immunological aspects of local radiotherapy: clinical relevance
Formenti, Silvia C
2010 Feb;9(45):119-124, Discovery medicine
Standard anti-cancer therapeutic modalities like chemotherapy and radiotherapy evoke host's reactions that include involvement of the immune system. Elucidation of these mechanisms offers the double advantage of enabling a more rational choice of cytotoxic therapy and exploring the combination with immunotherapy. Radiotherapy, a well established local anti-cancer approach, is a particularly interesting partner for immunotherapy, since it can be harnessed to specifically modify the immunogenicity of the primary tumor and its microenvironment, in the attempt to generate an in situ immunization of the host against a patient's own cancer
— id: 107786, year: 2010, vol: 9, page: 119, stat: Journal Article,

Low-dose radiation augments vasculogenesis signaling through HIF-1-dependent and -independent SDF-1 induction
Lerman, Oren Z; Greives, Matthew R; Singh, Sunil P; Thanik, Vishal D; Chang, Christopher C; Seiser, Natalie; Brown, Daniel J; Knobel, Denis; Schneider, Robert J; Formenti, Silvia C; Saadeh, Pierre B; Levine, Jamie P
2010 Nov 4;116(18):3669-3676, Blood
The inflammatory response to ionizing radiation (IR) includes a proangiogenic effect that could be counterproductive in cancer but can be exploited for treating impaired wound healing. We demonstrate for the first time that IR stimulates hypoxia-inducible factor-1alpha (HIF-1alpha) up-regulation in endothelial cells (ECs), a HIF-1alpha-independent up-regulation of stromal cell-derived factor-1 (SDF-1), as well as endothelial migration, all of which are essential for angiogenesis. 5 Gray IR-induced EC HIF-1alpha and SDF-1 expression was greater when combined with hypoxia suggesting an additive effect. While small interfering RNA silencing of HIF-1alpha mRNA and abolition of HIF-1alpha protein induction down-regulated SDF-1 induction by hypoxia alone, it had little effect on SDF-1 induction by IR, demonstrating an independent pathway. SDF-1-mediated EC migration in hypoxic and/or radiation-treated media showed IR induced strong SDF-1-dependent migration of ECs, augmented by hypoxia. IR activates a novel pathway stimulating EC migration directly through the expression of SDF-1 independent of HIF-1alpha induction. These observations might be exploited for stimulation of wound healing or controlling tumor angiogenesis
— id: 138185, year: 2010, vol: 116, page: 3669, stat: Journal Article,

Prone Hypo-fractionated Whole Breast Radiation without a Concomitant Boost: Comparative Effectiveness of Intensity Modulated Radiation Therapy (IMRT) vs. 3D-conformal Radiation Therapy (3D-CRT)
Min, C.; Hardee, M. E.; Pope, S.; Becker, S. J.; Lymberis, S. C.; DeWyngaert, K.; Formenti, S. C.
2010 OCT 13 ;78(3):S567-S567, International journal of radiation oncology biology physics
— id: 114021, year: 2010, vol: 78, page: S567, stat: Journal Article,

Interfraction and Intrafraction Setup Variability for Prone Breast Radiation Therapy
Mitchell, James; Formenti, Silvia C; DeWyngaert, J Keith
2010 Apr;76(5):1571-1577, International journal of radiation oncology biology physics
PURPOSE: To report the interfraction and intrafraction setup variation for prone breast radiotherapy and to determine an appropriate clinical tumor volume (CTV) to planning target volume (PTV)_ margin to account for motion and positional uncertainties. METHODS AND MATERIALS: Ten consecutive patients were prospectively enrolled in a protocol of accelerated, hypofractionated prone breast irradiation. Portal images were acquired using an electronic portal imaging device in cine mode. Interfraction setup error was determined by comparing the first image from each fraction with the digitally reconstructed radiograph. The intrafraction motion was determined by evaluating every image acquired during each fraction and measuring the maximum displacement of an external fiducial and the breast surface. Mean values and 95% confidence intervals (CI) were calculated. Based on these results, a CTV to PTV expansion was derived using the equation M = 2.5Sigma(tot) + 0.7sigma(tot.) RESULTS: The mean interfraction setup variability for the fiducial was 0.08 cm (CI: 0.02-0.14) in the anterior to posterior (AP) direction and -0.04 cm (CI: -0.07-0.00) in the superior to inferior (SI) direction. The mean interfraction variability of the breast surface was -0.14 cm (CI: -0.24 to -0.04) in the AP direction. The mean intrafraction displacements of the fiducial and the breast surface were 0.13 cm (CI: 0.12-0.15) and 0.15 cm (CI: 0.14-0.17), respectively. Using the systematic and random errors for the external fiducial, the calculated CTV to PTV expansion was 1.4 cm. CONCLUSIONS: Acceptable interfraction and intrafraction variability were demonstrated. The findings resulted in a CTV to PTV expansion of 1.4 cm
— id: 105481, year: 2010, vol: 76, page: 1571, stat: Journal Article,

Radiotherapy Enhances Antitumor Effect of Anti-CD137 Therapy in a Mouse Glioma Model
Newcomb, Elizabeth W; Lukyanov, Yevgeniy; Kawashima, Noriko; Alonso-Basanta, Michelle; Wang, Shu-Chi; Liu, Mengling; Jure-Kunkel, Maria; Zagzag, David; Demaria, Sandra; Formenti, Silvia C
2010 Apr;173(4):426-432, Radiation research
Abstract Previously, we reported that peripheral vaccination of mice with modified autologous tumor cells secreting granulocyte-macrophage colony-stimulating factor (GM-CSF) combined with ionizing radiation to the whole brain cured 50% of mice using a syngeneic, intracranial model of murine high-grade glioma. Here, we tested the combination of radiotherapy (4 Gy x 2) with an immunotherapeutic approach using an anti-CD137 antibody directed to the co-stimulatory molecule CD137. The CD137 antibody has shown promise in generating effective antitumor responses in several animal models and has demonstrated a favorable toxicity profile in the clinic. The combination of radiation and anti-CD137 therapy resulted in complete tumor eradication and prolonged survival in six of nine (67%) mice with established brain tumors (P = 0.0009). Five of six (83%) long-term survivors in the combination group demonstrated antitumor immunity by rejecting challenge tumors. Antitumor immunity was associated with an increased number of tumor-infiltrating lymphocytes (TILs) in brain tumors and increased tumor-specific production of gammaIFN. In view of the finding that radiation enhanced the antitumor effect of anti-CD137 therapy, this approach should be studied further for clinical translation
— id: 108807, year: 2010, vol: 173, page: 426, stat: Journal Article,

Decreasing temporal lobe dose with five-field intensity-modulated radiotherapy for treatment of pituitary macroadenomas
Parhar, Preeti K; Duckworth, Tamara; Shah, Parinda; DeWyngaert, J Keith; Narayana, Ashwatha; Formenti, Silvia C; Shah, Jinesh N
2010 Oct 1;78(2):379-384, International journal of radiation oncology biology physics
PURPOSE: To compare temporal lobe dose delivered by three pituitary macroadenoma irradiation techniques: three-field three-dimensional conformal radiotherapy (3D-CRT), three-field intensity-modulated radiotherapy (3F IMRT), and a proposed novel alternative of five-field IMRT (5F IMRT). METHODS AND MATERIALS: Computed tomography-based external beam radiotherapy planning was performed for 15 pituitary macroadenoma patients treated at New York University between 2002 and 2007 using: 3D-CRT (two lateral, one midline superior anterior oblique [SAO] beams), 3F IMRT (same beam angles), and 5F IMRT (same beam angles with additional right SAO and left SAO beams). Prescription dose was 45 Gy. Target volumes were: gross tumor volume (GTV) = macroadenoma, clinical target volume (CTV) = GTV, and planning target volume = CTV + 0.5 cm. Structure contouring was performed by two radiation oncologists guided by an expert neuroradiologist. RESULTS: Five-field IMRT yielded significantly decreased temporal lobe dose delivery compared with 3D-CRT and 3F IMRT. Temporal lobe sparing with 5F IMRT was most pronounced at intermediate doses: mean V25Gy (% of total temporal lobe volume receiving >/=25 Gy) of 13% vs. 28% vs. 29% for right temporal lobe and 14% vs. 29% vs. 30% for left temporal lobe for 5F IMRT, 3D-CRT, and 3F IMRT, respectively (p < 10(-7) for 5F IMRT vs. 3D-CRT and 5F IMRT vs. 3F IMRT). Five-field IMRT plans did not compromise target coverage, exceed normal tissue dose constraints, or increase estimated brain integral dose. CONCLUSIONS: Five-field IMRT irradiation technique results in a statistically significant decrease in the dose to the temporal lobes and may thus help prevent neurocognitive sequelae in irradiated pituitary macroadenoma patients
— id: 138373, year: 2010, vol: 78, page: 379, stat: Journal Article,

Five-year Results of Preoperative Paclitaxel with Concurrent Radiation Therapy in Locally Advanced Breast Cancer: Pathological Response Predicts for Survival
Schneider, R. J.; Formenti, S. C.; Chakravarthy, A.; Adams, S.; Spicer, D.; Lymberis, S.; Goldberg, J. D.; Pietenpol, J. A.
2010 OCT 13 ;78(3):S219-S219, International journal of radiation oncology biology physics
— id: 114016, year: 2010, vol: 78, page: S219, stat: Journal Article,

Translational control in cancer
Silvera, Deborah; Formenti, Silvia C; Schneider, Robert J
2010 Apr;10(4):254-266, Nature reviews. Cancer
Remarkable progress has been made in defining a new understanding of the role of mRNA translation and protein synthesis in human cancer. Translational control is a crucial component of cancer development and progression, directing both global control of protein synthesis and selective translation of specific mRNAs that promote tumour cell survival, angiogenesis, transformation, invasion and metastasis. Translational control of cancer is multifaceted, involving alterations in translation factor levels and activities unique to different types of cancers, disease stages and the tumour microenvironment. Several clinical efforts are underway to target specific components of the translation apparatus or unique mRNA translation elements for cancer therapeutics
— id: 115327, year: 2010, vol: 10, page: 254, stat: Journal Article,

Cutaneous low-dose radiation increases tissue vascularity through upregulation of angiogenic and vasculogenic pathways
Thanik, Vishal D; Chang, Christopher C; Lerman, Oren Z; Greives, Matthew R; Le, Huong; Warren, Stephen M; Schneider, Robert J; Formenti, Sylvia C; Saadeh, Pierre B; Levine, Jamie P
2010 ;47(6):472-480, Journal of vascular research
BACKGROUND/AIMS: Neovascularization involves angiogenesis and vasculogenesis mediated by cytokines and soluble chemokines. The predominant stimulus is ischemia, however, recent data suggest that ionizing radiation (IR) has angiogenic potential. In this study we evaluated whether IR increases vascularity and perfusion in vivo. METHODS: In wild-type mice, a full-thickness, pedicled skin flap was created and isolated for localized irradiation at a dose of 5 Gy. Serial Doppler analysis of the flap was performed. The skin flaps were then harvested at various time points for vascularity and histologic analysis. Blood was concurrently harvested for serum and hematopoietic progenitor cell population analysis. RESULTS: IR to an ischemic flap augmented the angiogenic cytokines SDF-1 and VEGF. Serum MMP-9 and s-kit levels, which are critical for progenitor cell mobilization, were also increased. When hematopoietic progenitor cells were evaluated by Sca1+/Flk1+ cells, a correlate 2-fold increase was seen compared to controls. When the flaps were examined, both vascularity and perfusion were increased. CONCLUSION: In this study we demonstrate that local, low-dose IR upregulates angiogenic chemokines and results in progenitor cell mobilization to the systemic circulation. There is a resultant increase in the vascularity of the irradiated flap, suggesting that the pro-angiogenic effects of IR can be harnessed locally
— id: 113939, year: 2010, vol: 47, page: 472, stat: Journal Article,

NYU Prone Accelerated Partial Breast Irradiation: Compliance to the Dosimetry Requirements of RTOG-0413
Wen, B.; Lymberis, S.; Formenti-Ujlaki, G. F.; Magnolfi, C.; Zhao, X.; Chang, J.; deWyngaert, K.; Jozsef, G.; Formenti, S. C.
2010 OCT 13 ;78(3):S256-S256, International journal of radiation oncology biology physics
— id: 114018, year: 2010, vol: 78, page: S256, stat: Journal Article,

A support vector machine (SVM) for predicting preferred treatment position in radiotherapy of patients with breast cancer
Zhao, Xuan; Wong, Edward K; Wang, Yao; Lymberis, Stella; Wen, Bixiu; Formenti, Silvia; Chang, Jenghwa
2010 Oct;37(10):5341-5350, Medical physics
PURPOSE: NYU 05-181 protocol compared the CT simulation in both supine and prone positions for 400 patients with breast cancer (200 left-breast and 200 right-breast) to identify which setup is better at sparing heart and lung involvement in the treatment process. The results demonstrated that all right-breast patients benefited from the prone treatment position, while for left-breast patients, 85% were better treated prone and 15% were better treated supine. Using the clinical data collected from this protocol, the authors aimed at developing an automated tool capable of identifying which of the left-breast cancer patients are better treated supine without obtaining a second CT scan in the supine position. METHODS: Prone CT scans from 198 of the 200 left-breast cancer patients enrolled in NYU 05-181 protocol were deidentified and exported to a dedicated research planning workstation. Three-dimensional geometric features of the organs at risk and tumor bed were extracted. A two-stage classifier was used to classify patients into the prone class or the supine class. In the first stage, the authors use simple thresholding to divide the patients into two groups based on their in-field heart volume. For patients with in-field heart volume < or = 0.1 cc, the prone position was chosen as the preferred treatment position. Patients with in-field heart volume > 0.1 cc will be further classified in the second stage by a weighted support vector machine (SVM). The weight parameters of the SVM were adjusted to maximize the specificity [true-supine/(true-supine+false-prone)] at the cost of lowering but still maintaining reasonable sensitivity [true-prone/(true-prone+false-supine)]. The authors used K-fold cross validations to test the performance of the SVM classifier. A feature selection algorithm was also used to identify features that give the best classification performance. RESULTS: After the first stage, 49 of the 198 left-breast cancer patients were found to have > 0.1 cc of in-field heart volume. The three geometric features of heart orientation, distance between heart and tumor, and in-field lung were selected by the feature selection algorithm in the second stage of the two-stage classifier to give the best predefined weighted accuracy. The overall sensitivity and specificity of the proposed method were found to be 90.4% and 99.3%, respectively. Using two-stage classification, the authors reduced the proportion of prone-treated patients that need a second supine CT scan down to 16.3/170 or 9.6%, as compared to 21/170 or 12.4% when the authors use only the first stage (thresholding) for classification. CONCLUSIONS: The authors' study showed that a feature-based classifier is feasible for predicting the preferred treatment position, based on features extracted from prone CT scans. The two-stage classifier achieved very high specificity at an acceptable expense of sensitivity
— id: 115326, year: 2010, vol: 37, page: 5341, stat: Journal Article,

Lack of Hormone Receptor Expression is Associated with Pathological Response in Locally Advanced Breast Cancer Patients Treated with Neoadjuvant Concurrent Chemoradiation
Adams, S; Donach, M; Singh, B; Goldberg, JD; Formenti, SC
2009 NOV ;75(3):S220-S221, International journal of radiation oncology biology physics
— id: 106177, year: 2009, vol: 75, page: S220, stat: Journal Article,

Coverage of axillary lymph nodes in supine vs. prone breast radiotherapy
Alonso-Basanta, Michelle; Ko, Jane; Babcock, Melissa; Dewyngaert, J Keith; Formenti, Silvia C
2009 Mar 1;73(3):745-751, International journal of radiation oncology biology physics
PURPOSE: To compare the dosimetry of target and normal tissue when tangents with the breast tissue were applied in a subset of breast cancer patients who had undergone computed tomography (CT) planning both supine and prone. METHODS AND MATERIALS: The CT images of 20 patients who had undergone simulation in supine and prone positions were used for planning. The axillary lymph node regions (level I-III), breast tissue, tumor bed, heart, and bilateral lungs were manually contoured. Standard tangent fields were designed for the whole breast to deliver a prescribed dose of 50 Gy. Dose-volume histograms were compared between the two sets. RESULTS: In each patient, coverage of breast tissue and tumor bed was readily achieved by either technique. In either position, treatment of the nodal regions was inadequate. On average, the mean dose to the nodal regions for levels I-III was approximately 50% less in the prone as compared with the supine position. The mean ipsilateral lung volume receiving 95% of the prescribed dose was 6.3% in the supine position compared to 0.43% in the prone position. When planned supine, the mean heart volume receiving 30 Gy was 0.56% compared with 0.30% in the prone position. CONCLUSIONS: Planning in either position was found to achieve adequate coverage of the breast tissue and tumor bed for all patients. Lung was better spared prone. Coverage of axillary nodes was inadequate in either position, but further reduced in the prone vs. supine position. The choice of optimal setup should take into considerations stage and risk of nodal recurrence
— id: 93548, year: 2009, vol: 73, page: 745, stat: Journal Article,

Mammography in developing countries: the risks associated with globalizing the experiences of the Western world
Arslan, Alan A; Formenti, Silvia C
2009 Mar;6(3):136-137, Nature clinical practice. Oncology
— id: 93550, year: 2009, vol: 6, page: 136, stat: Journal Article,

Platinum compounds and radiation
Baer L; Muggia F; Formenti S
Platinum and other heavy metal compounds in cancer chemotherapy : molecular mechanisms and clinical applications New York : Humana Press, 2009,
— id: 5323, year: 2009, vol: , page: 211, stat: Chapter,

Dose to the body organs from IMRT and 3D-CRT breat radiotherapy : prone and supine
Becker S; Elliston C; Jozsef G; DeWyngaert JK; Chang J; Brenner D; Formenti S
2009 ;35:2597-2597, Medical physics
— id: 123218, year: 2009, vol: 35, page: 2597, stat: Journal Article,

Regulation of protein synthesis by ionizing radiation
Braunstein, Steve; Badura, Michelle L; Xi, Qiaoran; Formenti, Silvia C; Schneider, Robert J
2009 Nov;29(21):5645-5656, Molecular & cellular biology
Ionizing radiation (IR) is a physiologically important stress to which cells respond by the activation of multiple signaling pathways. Using a panel of immortalized and transformed breast epithelial cell lines, we demonstrate that IR regulation of protein synthesis occurs in nontransformed cells and is lost with transformation. In nontransformed cells, IR rapidly activates the MAP kinases ERK1/2, resulting in an early transient increase in cap-dependent mRNA translation that involves mTOR and is radioprotective, enhancing the translation of a subset of mRNAs encoding proteins involved in DNA repair and cell survival. Following a transient increase in translation, IR-sensitive (nontransformed) cells inhibit cap-dependent protein synthesis through a mechanism that involves activation of p53, induction of Sestrin 1 and 2 genes, and stimulation of AMP kinase, inhibiting mTOR and hypophosphorylating 4E-BP1. IR is shown to block proteasome-mediated decay of 4E-BP1, increasing its abundance and the sequestration of eIF4E. The IR signal that impairs mTOR-dependent protein synthesis at late times is assembly of the DNA damage response machinery, consisting of Mre11, Rad50, and NBS1 (MRN); activation of the MRN complex kinase ATM; and p53. These results link genotoxic signaling from the DNA damage response complex to the control of protein synthesis
— id: 104346, year: 2009, vol: 29, page: 5645, stat: Journal Article,

Dose-dependent effect of radiation on angiogenic and angiostatic CXC chemokine expression in human endothelial cells
Chang, Christopher C; Lerman, Oren Z; Thanik, Vishal D; Scharf, Carrie L; Greives, Matthew R; Schneider, Robert J; Formenti, Sylvia C; Saadeh, Pierre B; Warren, Stephen M; Levine, Jamie P
2009 Dec;48(3):295-302, Cytokine
Blood vessel growth is regulated by angiogenic and angiostatic CXC chemokines, and radiation is a vasculogenic stimulus. We investigated the effect of radiation on endothelial cell chemokine signaling, receptor expression, and migration and apoptosis. Human umbilical vein endothelial cells were exposed to a single fraction of 0, 5, or 20Gy of ionizing radiation (IR). All vasculogenic chemokines (CXCL1-3/5-8) increased 3-13-fold after 5 or 20Gy IR. 20Gy induced a marked increase (1.6-4-fold) in angiostatic CXC chemokines. CXCR4 expression increased 3.5 and 7-fold at 48h after 5 and 20Gy, respectively. Bone marrow progenitor cell chemotaxis was augmented by conditioned media from cells treated with 5Gy IR. Whereas 5Gy markedly decreased intrinsic cell apoptosis (0Gy=16%+/-3.6 vs. 5Gy=4.5%+/-0.3), 20Gy increased it (21.4%+/-1.2); a reflection of pro-survival angiogenic chemokine expression. Radiation induces a dose-dependent increase in pro-angiogenic CXC chemokines and CXCR4. In contrast, angiostatic chemokines and apoptosis were induced at higher (20Gy) radiation doses. Cell migration improved significantly following 5Gy, but not 20Gy IR. Collectively, these data suggest that lower doses of IR induce an angiogenic cascade while higher doses produce an angiostatic profile
— id: 104228, year: 2009, vol: 48, page: 295, stat: Journal Article,

A Support Vector Machine (SVM) Classifier Enables Prediction of Optimal Setup, Prone versus Supine, in Left Breast Cancer Patients
Chang, J; Zhao, X; Wong, E; Wang, Y; Lymberis, S; Formenti, S
2009 NOV ;75(3):S218-S219, International journal of radiation oncology biology physics
— id: 106175, year: 2009, vol: 75, page: S218, stat: Journal Article,

Inhibition of Integrin beta 6 Prevents Radiation-induced Apoptosis of Intestinal Crypt Cells
Cheng, SK; Horan, GS; Weinreb, PH; Violette, SM; Formenti, SC; Munger, JS
2009 NOV ;75(3):S169-S170, International journal of radiation oncology biology physics
— id: 106170, year: 2009, vol: 75, page: S169, stat: Journal Article,

Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody
Dewan, M Zahidunnabi; Galloway, Ashley E; Kawashima, Noriko; Dewyngaert, J Keith; Babb, James S; Formenti, Silvia C; Demaria, Sandra
2009 Sep 1;15(17):5379-5388, Clinical cancer research
PURPOSE: This study tested the hypothesis that the type of dose fractionation regimen determines the ability of radiotherapy to synergize with anti-CTLA-4 antibody. EXPERIMENTAL DESIGN: TSA mouse breast carcinoma cells were injected s.c. into syngeneic mice at two separate sites, defined as a 'primary' site that was irradiated and a 'secondary' site outside the radiotherapy field. When both tumors were palpable, mice were randomly assigned to eight groups receiving no radiotherapy or three distinct regimens of radiotherapy (20 Gy x 1, 8 Gy x 3, or 6 Gy x 5 fractions in consecutive days) in combination or not with 9H10 monoclonal antibody against CTLA-4. Mice were followed for tumor growth/regression. Similar experiments were conducted in the MCA38 mouse colon carcinoma model. RESULTS: In either of the two models tested, treatment with 9H10 alone had no detectable effect. Each of the radiotherapy regimens caused comparable growth delay of the primary tumors but had no effect on the secondary tumors outside the radiation field. Conversely, the combination of 9H10 and either fractionated radiotherapy regimens achieved enhanced tumor response at the primary site (P < 0.0001). Moreover, an abscopal effect, defined as a significant growth inhibition of the tumor outside the field, occurred only in mice treated with the combination of 9H10 and fractionated radiotherapy (P < 0.01). The frequency of CD8+ T cells showing tumor-specific IFN-gamma production was proportional to the inhibition of the secondary tumor. CONCLUSIONS: Fractionated but not single-dose radiotherapy induces an abscopal effect when in combination with anti-CTLA-4 antibody in two preclinical carcinoma models
— id: 101960, year: 2009, vol: 15, page: 5379, stat: Journal Article,

Other new radiotherapy techniques
Formenti S
2009 Jun 23;11 Suppl 1:S10-S10, Breast cancer research
— id: 138409, year: 2009, vol: 11 Suppl 1, page: S10, stat: Journal Article,

Other new radiotherapy techniques
Formenti S.C.
2009 ;11:S5-S5, Breast cancer research
Objective To report the NYU research on novel radiation therapy of breast cancer. Radiation therapy has enabled effective breast preservation in the majority of newly diagnosed breast cancer patients. This milestone in the history of breast cancer management is currently revisited to identify the optimal selection of target and fractionation, while assuring minimal radiation exposure of normal tissues adjacent to the breast. Methods Five consecutive prospective trials explored hypofractionated, accelerated regimens of breast radiotherapy that also aim at optimal normal tissue sparing. Results After pilot-testing a 3-week prone regimen of IMRT to the breast with a concomitant boost to the tumor bed, we have prospectively studied in a cohort of 400 women whether a prone versus a supine setup for treatment was superior at sparing lung and heart tissue, while assuring target (index breast) coverage. The results of this trial indicate that the prone setup is superior in >90% of patients. The prone setup also characterizes our two studies of partial breast irradiation delivered over five fractions of 6 Gy each. At NYU this approach is only offered to the subset of patients at the lowest risk of local recurrence after breast-conserving surgery, postmenopausal women with T1 lesions, resected with negative margins. Results at a median follow-up of 5 years demonstrate 2% local recurrence rate. Conclusions Breast radiotherapy after breast-conserving surgery can be safely delivered over 3 weeks. A prone technique enables optimal sparing of the lung and heart in the majority of patients. Current research focuses on a prone setup that includes level III and supraclavicular lymph nodes in patients with positive lymph nodes, to enhance sparing of the lung and heart
— id: 123216, year: 2009, vol: 11, page: S5, stat: Journal Article,

Results of NYU 05-181: A Prospective Trial to Determine Optimal Position (Prone versus Supine) for Breast Radiotherapy
Formenti, S; Lymberis, S; Parhar, P; Fenton-Kerimian, M; Magnolfi, C; Wen, B; Chang, J; DeWyngaert, J
2009 NOV ;75(3):S203-S204, International journal of radiation oncology biology physics
— id: 106173, year: 2009, vol: 75, page: S203, stat: Journal Article,

Systemic effects of local radiotherapy
Formenti, Silvia C; Demaria, Sandra
2009 Jul;10(7):718-726, Lancet oncology
Radiotherapy is generally used to treat a localised target that includes cancer. Increasingly, evidence indicates that radiotherapy recruits biological effectors outside the treatment field and has systemic effects. We discuss the implications of such effects and the role of the immune system in standard cytotoxic treatments. Because the effects of chemotherapy and radiotherapy are sensed by the immune system, their combination with immunotherapy presents a new therapeutic opportunity. Radiotherapy directly interferes with the primary tumour and possibly reverses some immunosuppressive barriers within the tumour microenvironment-ideally, recovering the role of the primary tumour as an immunogenic hub. Local radiation also triggers systemic effects that can be used in combination with immunotherapy to induce responses outside the radiation field
— id: 100625, year: 2009, vol: 10, page: 718, stat: Journal Article,

Hypofractionated Whole Breast Radiotherapy: A Prone Adaptation of the Canadian Fractionation
Hardee, ME; Raza, S; Becker, SJ; Lymberis, SC; DeWyngaert, K; Formenti, SC
2009 ;75(3):S198-S198, International journal of radiation oncology biology physics
— id: 109259, year: 2009, vol: 75, page: S198, stat: Journal Article,

Prospective Study of Cone-beam CT (CBCT) Guidance for Prone Accelerated Partial Breast Irradiation (APBI)
Jozsef, G; Lymberis, SC; DeWyngaert, KJ; Formenti, SC
2009 ;75(3):S571-S572, International journal of radiation oncology biology physics
— id: 109260, year: 2009, vol: 75, page: S571, stat: Journal Article,

Comparison of Cardiac Position among Left Breast Cancer Patients Treated Supine or Prone on NYU Protocol 05-181
Lymberis, S; Kumaev, BB; Wen, B; Joszef, G; DeWyngaert, JK; Chang, J; Formenti, SC
2009 NOV ;75(3):S212-S212, International journal of radiation oncology biology physics
— id: 106174, year: 2009, vol: 75, page: S212, stat: Journal Article,

Anti-integrin beta 6 Therapy Reverses Radiation-induced Lung Fibrosis
Munger, J; Cheng, SK; Horan, GS; Weinreb, PH; Violette, SM; Formenti, SC
2009 NOV ;75(3):S173-S173, International journal of radiation oncology biology physics
— id: 106171, year: 2009, vol: 75, page: S173, stat: Journal Article,

Local Radiotherapy Rescues Responsiveness to Anti-CD137 Immunotherapy in a Mouse Model of Advanced Breast Cancer
Pilones, KA; Kawashima, N; Formenti, SC; Demaria, S
2009 DEC 15 ;69(24):752S-752S, Cancer research
— id: 106455, year: 2009, vol: 69, page: 752S, stat: Journal Article,

Invariant natural killer T cells regulate breast cancer response to radiation and CTLA-4 blockade
Pilones, Karsten A; Kawashima, Noriko; Yang, Anne Marie; Babb, James S; Formenti, Silvia C; Demaria, Sandra
2009 Jan 15;15(2):597-606, Clinical cancer research
PURPOSE: Immunoregulatory and suppressive mechanisms represent major obstacles to the success of immunotherapy in cancer patients. We have shown that the combination of radiotherapy to the primary tumor and CTL-associated protein 4 (CTLA-4) blockade induces antitumor immunity, inhibiting metastases and extending the survival of mice bearing the poorly immunogenic and highly metastatic 4T1 mammary carcinoma. Similarly to patients with metastatic cancer, however, mice were seldom cured. Here we tested the hypothesis that invariant natural killer T (iNKT) cells, a subset with unique regulatory functions, can regulate the response to radiotherapy and CTLA-4 blockade. EXPERIMENTAL DESIGN: The growth of 4T1 primary tumors and lung metastases was compared in wild-type and iNKT cell-deficient (iNKT-/-) mice. Treatment was started on day 13 when the primary tumors were palpable. Mice received radiotherapy to the primary tumor in two doses of 12 Gy in combination or not with 9H10 monoclonal antibody against CTLA-4. Response to treatment was assessed by measuring primary tumor growth delay/regression, survival, and number of lung metastases. RESULTS: The response to radiotherapy plus 9H10 was markedly enhanced in the absence of iNKT cells, with 50% of iNKT-/- versus 0% of wild-type mice showing complete tumor regression, long-term survival, and resistance to a challenge with 4T1 cells. Administration of the iNKT cell activator alpha-galactosylceramide did not enhance the response of wild-type mice to radiotherapy plus 9H10. Tumor-infiltrating iNKT cells were markedly reduced in wild-type mice treated with radiotherapy plus 9H10. CONCLUSIONS: iNKT cells play a major role in regulating the response to treatment with local radiotherapy and CTLA-4 blockade
— id: 93549, year: 2009, vol: 15, page: 597, stat: Journal Article,

Six-week Standard Fractionation Breast Radiotherapy versus Five-weeks with a Concomitant Boost: Acute and Late Toxicity
Raza, S; Lymberis, S; DeWyngaert, K; Fenton-Kerimian, M; Donach, M; Formenti, S
2009 NOV ;75(3):S219-S219, International journal of radiation oncology biology physics
— id: 106176, year: 2009, vol: 75, page: S219, stat: Journal Article,

Dosimetric analysis of prone versus supine concomitant boost IMRT technique for whole breast radiotherapy: prone is better in reducing cardiac dose for left sided breast cancer
Reves, V; Lymberis, SC; Becker, S; Racsa, M; Jozsef, G; DeWyngaert, K; Formenti, SC
2009 ;69(2):339S-339S, Cancer research
— id: 109258, year: 2009, vol: 69, page: 339S, stat: Journal Article,

Synergy of Radiation and Immune Therapy in Tumor Eradication
Ruocco, MG; Kawashima, N; Huang, J; Formenti, S; Dustin, ML; Demaria, S
2009 NOV-DEC ;32(9):995-995, Journal of immunotherapy (Hagerstown)
— id: 105633, year: 2009, vol: 32, page: 995, stat: Journal Article,

IMRT versus Fixed-beam Technique for Regional Nodal Coverage in Breast Cancer Patients in a Prone versus Supine Treatment Position
Sethi, RA; No, H; Jozsef, G; Formenti, SC
2009 NOV ;75(3):S203-S203, International journal of radiation oncology biology physics
— id: 106172, year: 2009, vol: 75, page: S203, stat: Journal Article,

Essential role for eIF4GI overexpression in the pathogenesis of inflammatory breast cancer
Silvera, Deborah; Arju, Rezina; Darvishian, Farbod; Levine, Paul H; Zolfaghari, Ladan; Goldberg, Judith; Hochman, Tsivia; Formenti, Silvia C; Schneider, Robert J
2009 Jul;11(7):903-908, Nature cell biology
Inflammatory breast cancer (IBC) is the most lethal form of primary breast cancer. IBC lethality derives from generation of tumour emboli, which are non-adherent cell clusters that rapidly spread by a form of continuous invasion known as passive metastasis. In most cancers, expression of E-cadherin, an epithelial marker, is indicative of low metastatic potential. In IBC, E-cadherin is overexpressed and supports formation of tumour emboli by promoting tumour cell interactions rather than adherence to stroma. E-cadherin, a surface component of adherens junctions, is anchored by interaction with p120 catenin (p120). We show that the unique pathogenic properties of IBC result in part from overexpression of the translation initiation factor eIF4GI in most IBCs. eIF4GI reprograms the protein synthetic machinery for increased translation of mRNAs with internal ribosome entry sites (IRESs) that promote IBC tumour cell survival and formation of tumour emboli. Overexpression of eIF4GI promotes formation of IBC tumour emboli by enhancing translation of IRES-containing p120 mRNAs. These findings provide a new understanding of translational control in the development of advanced breast cancer
— id: 100610, year: 2009, vol: 11, page: 903, stat: Journal Article,

Concurrent radiotherapy, paclitaxel and dose escalating carboplatin in the treatment of cervical cancer--a phase I study
Addeo, Daniela; Blank, Stephanie; Muggia, Franco; Formenti, Silvia
2008 Sep-Oct;28(5B):3143-3146, Anticancer research
BACKGROUND: Concurrent radiation therapy (RT) and chemotherapy represents the standard treatment of locally advanced cervical cancer. This study was designed to determine the feasibility and toxicity of concomitant administration of RT with twice per week paclitaxel and carboplatin. MATERIALS AND METHODS: Nine women with cervical cancer stage IB2-IVA were treated with standard RT and twice per week paclitaxel at a dose of 30 mg/m2 with carboplatin in escalating doses starting at an AUC of 5. RESULTS: One out of the four patients who received carboplatin at AUC 5 developed grade III toxicity according to the National Cancer Institute (NCI) grading system. Two out of the five patients who received carboplatin at AUC 6 developed grade III toxicity. A clinical response was achieved in 8 patients (89%), with a complete response (CR) in 5 patients (56%). CONCLUSION: Combining RT with twice weekly paclitaxel (30 mg/m2) and carboplatin (AUC of 6) is a tolerated regimen, active in controlling locally advanced cervical cancer
— id: 93551, year: 2008, vol: 28, page: 3143, stat: Journal Article,

Acquisition of stable inducible up-regulation of nuclear factor-kappaB by tumor necrosis factor exposure confers increased radiation resistance without increased transformation in breast cancer cells
Braunstein, Steve; Formenti, Silvia C; Schneider, Robert J
2008 Jan;6(1):78-88, Molecular cancer research
High-grade breast cancers are better adapted to hypoxia and more resistant to chemotherapy and radiotherapy. Constitutive activation of the transcription factor nuclear factor-kappaB (NF-kappaB) increases in breast tumors and in breast cancer cell lines, where it promotes chemoradiation resistance, in part by activation of antiapoptotic genes. The role for up-regulation of NF-kappaB in breast cancer progression is less clear. Here, we first show that whereas the constitutive activity of NF-kappaB is incrementally elevated from immortalized breast epithelial to frank transformed invasive ductal breast cancer cell lines (~3-fold, +/-0.1-fold, P < 0.05), inflammatory cytokine-inducible activity is further increased (up to 9-fold, +/-0.9-fold, P < 0.05). We then show that inhibition of NF-kappaB activity selectively sensitizes transformed but not immortalized cells to killing by ionizing radiation or low levels of tumor necrosis factor (TNF) by up to 10-fold (+/-1-fold, P < 0.05) but has little effect on hypoxia-mediated cell death. Prolonged cultivation of immortalized and partially transformed cells in TNF selected for cells displaying stable constitutive and strongly inducible overexpression of NF-kappaB even in the absence of TNF. Stable acquisition of increased NF-kappaB activity conferred resistance to ionizing radiation or inflammatory cytokines, which was dependent on elevated NF-kappaB activity, but had no effect on transformation potential measured by in vitro and in vivo parameters. Thus, TNF and possibly other inflammatory cytokines in the tumor-stroma matrix likely select for breast cancer cells that stably overexpress NF-kappaB, leading to greater cancer cell survival. Greater cell survival despite increased genomic injury may permit increased acquisition of malignant genetic alterations as well as resistance to chemoradiation therapy
— id: 76463, year: 2008, vol: 6, page: 78, stat: Journal Article,

Objective evaluation of breast fibrosis in patients treated with accelerated partial breast irradiation (APBI) using the BTC-2000 device
Chao, K; Lymberis, S; Racsa, M; Fenton-Kerimian, M; Magnolti-Bozzi, C; Formenti, SC
2008 ;72(1):S189-S189, International journal of radiation oncology biology physics
— id: 109262, year: 2008, vol: 72, page: S189, stat: Journal Article,

Feasibility of accelerated whole-breast radiation in the treatment of patients with ductal carcinoma in situ of the breast
Constantine, Claire; Parhar, Preeti; Lymberis, Stella; Fenton-Kerimian, Maria; Han, Stephanie C; Rosenstein, Barry S; Formenti, Silvia C
2008 Jun;8(3):269-274, Clinical breast cancer
BACKGROUND: We report the results of a prospective trial investigating the use of accelerated, hypofractionated whole-breast radiation therapy after breast-conservation surgery for ductal carcinoma in situ (DCIS). PATIENTS AND METHODS: A total of 59 patients with a median age of 54 years (range, 36-78 years) completed a phase I/II study of hypofractionated radiation therapy for treatment of DCIS. Eligibility criteria included patients with mammographically detected DCIS, status after segmental mastectomy with negative margins, and no residual calcifications. All patients were treated with external-beam radiation therapy without a boost, over 3 weeks, to a total dose of 42 Gy to the entire breast (2.8 Gy per fraction in 15 fractions). To optimally spare heart and lung, 34 of the 59 patients (57%) were treated in the prone position. Twenty-nine of 59 patients (49%) received adjuvant hormonal therapy. RESULTS: Overall, radiation therapy was well tolerated, with modest acute toxicity limited to grade 1 radiation dermatitis (76%), breast edema (17%), and fatigue (12%). With a median follow-up of 36 months, late toxicities included grade 1 hyperpigmentation changes (85%), induration (66%), asymmetry (64%), and breast fibrosis (17%), with 3 cases of grade 2 fibrosis and 1 case of grade 2 hyperpigmentation. Among the patients with >or= 3 years of follow-up, cosmesis was scored as good to excellent in 21 patients (91%) and fair in 2 patients (9%). At the time of this report, no ipsilateral or contralateral breast recurrences have occurred. CONCLUSION: These data demonstrate the feasibility of treating the whole breast for DCIS with a hypofractionated regimen, with modest acute and late toxicity
— id: 80619, year: 2008, vol: 8, page: 269, stat: Journal Article,

CBCT enabled reconstruction of inter-fraction variation of dose distribution for partial breast irradiation
DeWyngaert, J; Lymberis, S; Addeo, D; Becker, S; Formenti, SC
2008 AUG ;72(1):S514-S514, International journal of radiation oncology biology physics
— id: 86798, year: 2008, vol: 72, page: S514, stat: Journal Article,

Decreased temporal lobe dose with 5-field IMRT for pituitary macroadenoma treatment
Duckworth, T; Parhar, P; Shah, P; DeWyngaert, K; Narayana, A; Formenti, SC; Shah, JN
2008 AUG ;72(1):S236-S236, International journal of radiation oncology biology physics
— id: 86796, year: 2008, vol: 72, page: S236, stat: Journal Article,

Strategies to enhance radiosensitivity in breast cancer
Formenti S.C.
2008 ;11(8):?-? e15, Breast Cancer Online : BCO
Radiotherapy is an important component in the treatment of breast cancer. However, the individual tumor response to radiation is variable, reflecting both the intrinsic properties of the tumor and its microenvironment as well as the different, inherited sensitivity of the patient's normal tissue when exposed to the effect of ionizing radiation. These differences have inspired research to discover the underlying signal transduction pathways and to understand when they pertain to the tumor, the host or both. In fact, understanding the mechanisms underlying radiosensitivity of breast cancer not only does it permit to design more effective radiation treatments, but it sheds light on the complexities of tumor-host interactions in this disease. copyright 2008 Cambridge University Press
— id: 86637, year: 2008, vol: 11, page: ?, stat: Journal Article,

Harnessing ionizing radiation to enhance immunotherapy: A paradigm shift
Formenti, S
2008 AUG ;22(9):1080-+, Oncology
— id: 86791, year: 2008, vol: 22, page: 1080, stat: Journal Article,

Abscopal response in irradiated patients: Results of a proof of principle trial
Formenti, SC; Friedman, K; Chao, K; Adams, S; Fenton-Kerimian, M; Donach, ME; Demaria, S
2008 AUG ;72(1):S6-S7, International journal of radiation oncology biology physics
— id: 86793, year: 2008, vol: 72, page: S6, stat: Journal Article,

Effects of chemoradiation on tumor-host interactions: the immunologic side
Formenti, Silvia C; Demaria, Sandra
2008 Mar 20;26(9):1562-1563, Journal of clinical oncology
— id: 76645, year: 2008, vol: 26, page: 1562, stat: Journal Article,

Local control by radiotherapy: is that all there is?
Formenti, Silvia C; Demaria, Sandra
2008 ;10(6):215-215, Breast cancer research
Radiotherapy is a local treatment modality employed in breast cancer to reduce local recurrence following surgery. The observed association of optimal local control with improved survival was not expected in a disease characterized by early systemic spread. The underlying mechanisms whereby the application of ionizing radiation to the primary tumor site can have systemic effects remain unclear and are the subject of much debate. In the present article we discuss the hypothesis that radiotherapy has unique biological effects and that, in addition to killing residual neoplastic cells after surgery is performed, it might favorably alter the microenvironment at the primary tumor site during the process of wound healing and the development of antitumor immune responses
— id: 93552, year: 2008, vol: 10, page: 215, stat: Journal Article,

Results of prospective trial to determine optimal patient positioning prone vs. supine for whole breast radiation
Lymberis, SC; Parhar, P; Yee, D; Roden, D; Jozsef, G; DeWyngaert, J; Formenti, SC
2008 ;72(1):S509-S509, International journal of radiation oncology biology physics
— id: 109263, year: 2008, vol: 72, page: S509, stat: Journal Article,

Prone-breast radiotherapy: too early for conclusions: in regard to Chino et Al. (Int j radiat oncol biol phys 2008;70:916-920)
Lymberis, Stella C; Formenti, Silvia C
2008 Sep 1;72(1):301-302, International journal of radiation oncology biology physics
— id: 93553, year: 2008, vol: 72, page: 301, stat: Journal Article,

Radiation-induced CXCL16 release by breast cancer cells attracts effector T cells
Matsumura, Satoko; Wang, Baomei; Kawashima, Noriko; Braunstein, Steve; Badura, Michelle; Cameron, Thomas O; Babb, James S; Schneider, Robert J; Formenti, Silvia C; Dustin, Michael L; Demaria, Sandra
2008 Sep 1;181(5):3099-3107, Journal of immunology
Recruitment of effector T cells to inflamed peripheral tissues is regulated by chemokines and their receptors, but the factors regulating recruitment to tumors remain largely undefined. Ionizing radiation (IR) therapy is a common treatment modality for breast and other cancers. Used as a cytocidal agent for proliferating cancer cells, IR in combination with immunotherapy has been shown to promote immune-mediated tumor destruction in preclinical studies. In this study we demonstrate that IR markedly enhanced the secretion by mouse and human breast cancer cells of CXCL16, a chemokine that binds to CXCR6 on Th1 and activated CD8 effector T cells, and plays an important role in their recruitment to sites of inflammation. Using a poorly immunogenic mouse model of breast cancer, we found that irradiation increased the migration of CD8(+)CXCR6(+) activated T cells to tumors in vitro and in vivo. CXCR6-deficient mice showed reduced infiltration of tumors by activated CD8 T cells and impaired tumor regression following treatment with local IR to the tumor and Abs blocking the negative regulator of T cell activation, CTLA-4. These results provide the first evidence that IR can induce the secretion by cancer cells of proinflammatory chemotactic factors that recruit antitumor effector T cells. The ability of IR to convert tumors into 'inflamed' peripheral tissues could be exploited to overcome obstacles at the effector phase of the antitumor immune response and improve the therapeutic efficacy of immunotherapy
— id: 81352, year: 2008, vol: 181, page: 3099, stat: Journal Article,

Antiangiogenic effects of noscapine enhance radioresponse for GL261 tumors
Newcomb, Elizabeth W; Lukyanov, Yevgeniy; Alonso-Basanta, Michelle; Esencay, Mine; Smirnova, Iva; Schnee, Tona; Shao, Yongzhao; Devitt, Mary Louise; Zagzag, David; McBride, William; Formenti, Silvia C
2008 Aug 1;71(5):1477-1484, International journal of radiation oncology biology physics
PURPOSE: To assess the effects of noscapine, a tubulin-binding drug, in combination with radiation in a murine glioma model. METHODS AND MATERIALS: The human T98G and murine GL261 glioma cell lines treated with noscapine, radiation, or both were assayed for clonogenic survival. Mice with established GL261 hind limb tumors were treated with noscapine, radiation, or both to evaluate the effect of noscapine on radioresponse. In a separate experiment with the same treatment groups, 7 days after radiation, tumors were resected and immunostained to measure proliferation rate, apoptosis, and angiogenic activity. RESULTS: Noscapine reduced clonogenic survival without enhancement of radiosensitivity in vitro. Noscapine combined with radiation significantly increased tumor growth delay: 5, 8, 13, and 18 days for control, noscapine alone, radiation alone, and the combination treatment, respectively (p < 0.001). To assess the effect of the combination of noscapine plus radiation on the tumor vasculature, tubule formation by the murine endothelial 2H11 cells was tested. Noscapine with radiation significantly inhibited tubule formation compared with radiation alone. By immunohistochemistry, tumors treated with the combination of noscapine plus radiation showed a decrease in BrdU incorporation, an increase in apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling, and a decrease in tumor vessel density compared with tumors treated with radiation alone. CONCLUSION: Noscapine enhanced the sensitivity of GL261 glioma tumors to radiation, resulting in a significant tumor growth delay. An antiangiogenic mechanism contributed to the effect. These findings are clinically relevant, particularly in view of the mild toxicity profile of this drug
— id: 82921, year: 2008, vol: 71, page: 1477, stat: Journal Article,

Optimizing the tumor response to ionizing radiation and immunotherapy by blocking VEGF
Pilones, KA; Formenti, SC; Demaria, S
2008 ;72(1):S168-S168, International journal of radiation oncology biology physics
— id: 109261, year: 2008, vol: 72, page: S168, stat: Journal Article,

Inhibition of integrin alpha(v)beta6, an activator of latent transforming growth factor-beta, prevents radiation-induced lung fibrosis
Puthawala, Khalid; Hadjiangelis, Nicos; Jacoby, Steven C; Bayongan, Emmanuel; Zhao, Zhicheng; Yang, Zhiwei; Devitt, Mary Louise; Horan, Gerald S; Weinreb, Paul H; Lukashev, Matvey E; Violette, Shelia M; Grant, Kristen S; Colarossi, Cristina; Formenti, Silvia C; Munger, John S
2008 Jan 1;177(1):82-90, American journal of respiratory & critical care medicine
RATIONALE: In experimental models, lung fibrosis is dependent on transforming growth factor (TGF)-beta signaling. TGF-beta is secreted in a latent complex with its propeptide, and TGF-beta activators release TGF-beta from this complex. Because the integrin alpha(v)beta6 is a major TGF-beta activator in the lung, inhibition of alpha(v)beta6-mediated TGF-beta activation is a logical strategy to treat lung fibrosis. OBJECTIVES: To determine, by genetic and pharmacologic approaches, whether murine radiation-induced lung fibrosis is dependent on alpha(v)beta6. METHODS: Wild-type mice, alpha(v)beta6-deficient (Itgb6-/-) mice, and mice heterozygous for a Tgfb1 mutation that eliminates integrin-mediated activation (Tgfb1(+/RGE)) were exposed to 14 Gy thoracic radiation. Some mice were treated with an anti-alpha(v)beta6 monoclonal antibody or a soluble TGF-beta receptor fusion protein. Alpha(v)beta6 expression was determined by immunohistochemistry. Fibrosis, inflammation, and gene expression patterns were assessed 20-32 weeks postirradiation. MEASUREMENTS AND MAIN RESULTS: Beta6 integrin expression increased within the alveolar epithelium 18 weeks postirradiation, just before onset of fibrosis. Itgb6-/- mice were completely protected from fibrosis, but not from late radiation-induced mortality. Anti-alpha(v)beta6 therapy (1-10 mg/kg/wk) prevented fibrosis, but only higher doses (6-10 mg/kg/wk) caused lung inflammation similar to that in Itgb6-/- mice. Tgfb1-haploinsufficient mice were also protected from fibrosis. CONCLUSIONS: Alpha(v)beta6-mediated TGF-beta activation is required for radiation-induced lung fibrosis. Together with previous data, our results demonstrate a robust requirement for alpha(v)beta6 in distinct fibrosis models. Inhibition of alphavbeta6-mediated TGF-beta activation is a promising new approach for antifibrosis therapy
— id: 75454, year: 2008, vol: 177, page: 82, stat: Journal Article,

eIF4GI links nutrient sensing by mTOR to cell proliferation and inhibition of autophagy
Ramirez-Valle, Francisco; Braunstein, Steve; Zavadil, Jiri; Formenti, Silvia C; Schneider, Robert J
2008 Apr 21;181(2):293-307, Journal of cell biology
Translation initiation factors have complex functions in cells that are not yet understood. We show that depletion of initiation factor eIF4GI only modestly reduces overall protein synthesis in cells, but phenocopies nutrient starvation or inhibition of protein kinase mTOR, a key nutrient sensor. eIF4GI depletion impairs cell proliferation, bioenergetics, and mitochondrial activity, thereby promoting autophagy. Translation of mRNAs involved in cell growth, proliferation, and bioenergetics were selectively inhibited by reduction of eIF4GI, as was the mRNA encoding Skp2 that inhibits p27, whereas catabolic pathway factors were increased. Depletion or overexpression of other eIF4G family members did not recapitulate these results. The majority of mRNAs that were translationally impaired with eIF4GI depletion were excluded from polyribosomes due to the presence of multiple upstream open reading frames and low mRNA abundance. These results suggest that the high levels of eIF4GI observed in many breast cancers might act to specifically increase proliferation, prevent autophagy, and release tumor cells from control by nutrient sensing
— id: 79095, year: 2008, vol: 181, page: 293, stat: Journal Article,

Phase I/II study of biweekly paclitaxel and radiation in androgen-ablated locally advanced prostate cancer
Sanfilippo, Nicholas J; Taneja, Samir S; Chachoua, Abraham; Lepor, Herbert; Formenti, Silvia C
2008 Jun 20;26(18):2973-2978, Journal of clinical oncology
PURPOSE: To determine the maximum-tolerated dose (MTD) of concurrent paclitaxel and radiation therapy (RT) in patients with locally advanced prostate cancer. MATERIALS AND METHODS: Eligible patients had T2-4 tumors with Gleason scores greater than 7 and/or PSA levels greater than 10 ng/mL and/or had tumors with pathologic stage TxN1. Hormonal ablation was initiated 3 months before RT and was given for 9 months. RT was delivered daily (1.8 Gy) with concurrent twice-weekly paclitaxel (30 mg/m(2)). The whole pelvis was irradiated to 39.6 Gy. The radiation dose was escalated as follows: 63 Gy, 66.6 Gy, 70.2 Gy, and 73.8 Gy. The last RT dose level was fixed at 73.8 Gy. RESULTs: Between January 2000 and October 2006, 22 patients were enrolled. The median age was 59 years (range, 48 to 72 years); the median PSA level was 22.4 ng/mL (range, 2.8 to 113 ng/mL). The number of patients per stage was as follows: three with T1, eight with T2, 11 with T3, and five with pN1 = 5. No grade 3 toxicities occurred at 63 Gy. Grade 3 diarrhea occurred in three patients at 66.6 Gy. The protocol then was amended to treat the prostate volume first followed by the whole pelvis. No grade 3 toxicities were observed at 70.2 Gy. One patient experienced grade 3 diarrhea at 73.8 Gy. Five additional patients were treated to 73.8 Gy without grade 3 toxicity, which established the MTD for combined paclitaxel and RT at 73.8 Gy. At 38 months median follow-up (range, 9 to 87 months), 21 (95%) of 22 patients are alive. Six (27%) of 22 experienced recurrence. CONCLUSION: Concurrent biweekly paclitaxel with RT is feasible, with an MTD of 73.8 Gy. Recovery of gonadal function occurs in the majority of patients. These results encourage testing in a phase III setting
— id: 79569, year: 2008, vol: 26, page: 2973, stat: Journal Article,

Betaig-h3 tumor suppressor gene expression is absent in human low-grade follicular lymphoma but not in high-grade follicular lymphoma
Shah, JN; Liu, C; Zhao, Y; Formenti, SC; Ibrahim, S
2008 AUG ;72(1):S472-S472, International journal of radiation oncology biology physics
— id: 86797, year: 2008, vol: 72, page: S472, stat: Journal Article,

Breast cancer clinical and translational research: analogies and implications for prostate cancer
Baer, Lea; Formenti, Silvia C
2007 ;9 Suppl 2:S28-S39, Reviews in urology
Breast and prostate cancer, respectively, are the most common cancers in women and in men in the United States. The management of locally advanced prostate cancer involves a multidisciplinary approach, bearing similarity to the therapeutic approach to breast cancer. Better understanding of the molecular biology of these cancers and the identification of the role played by the cancer stem cells and the tumor microenvironment may translate into better clinical decision making regarding risk classification and treatment allocation. A systematic assessment is presented of the many parallel evolutions in defining and treating high-risk breast cancer as they pertain to prostate cancer
— id: 93554, year: 2007, vol: 9 Suppl 2, page: S28, stat: Journal Article,

Penicillium populations in dry-cured ham manufacturing plants
Battilani, Paola; Pietri, V Amedeo; Giorni, Paola; Formenti, Silvia; Bertuzzi, Terenzio; Toscani, Tania; Virgili, Roberta; Kozakiewicz, Zofia
2007 Apr;70(4):975-980, Journal of food protection
Seven ham manufacturing plants were sampled for 1 year to assess the mycoflora present in the air and on hams, with special attention given to potential mycotoxin producers. Temperature and relative humidity were recorded in the ripening rooms. Maturing rooms held hams from 2 to 3 through 6 to 7 ripening months, and aging rooms held hams for the following 6 to 7 months, until the 14-month ripening point, when they were ready for the market. Mean temperatures and relative humidities registered during the study were 14.9 degrees C and 62.4%, respectively, in maturing rooms and 16.3 degrees C and 57.6% in aging rooms. Aspergilli and penicillia, potential mycotoxin producers, were isolated in all the plants from the air and the ham. Aspergilli represented 5% of the isolates, while penicillia were largely dominant, with Penicillium nalgiovense being the most represented species (around 60% of the penicillia), followed by Penicillium nordicum, with 10 and 26% of the penicillia isolated, respectively, from the air or the ham. Ochratoxin A production ability, checked in vitro at 250C, was observed in 50% of the P. nordicum isolates obtained both from the air and the ham. Air and ham surface contamination by penicillia was greater in the ripening rooms, where higher temperatures were registered. A certain correlation was also observed between air and ham surface contamination. On the basis of this study, P. nordicum, the ochratoxin A producer that is notable on proteinaceous substrates, is normally present in ham manufacturing plants in Italy, even though not a dominant species. Further studies are necessary to clarify and ensure if dry-curing conditions minimize the potential risk of ochratoxin A formation in the product
— id: 93556, year: 2007, vol: 70, page: 975, stat: Journal Article,

Cone-beam CTs of the prone breast
Becker, SJ; Jozsef, G; DeWyngaert, JK; Formenti, S
2007 JAN ;69(3):S721-S721, International journal of radiation oncology biology physics
— id: 87201, year: 2007, vol: 69, page: S721, stat: Journal Article,

A hypoxia-controlled cap-dependent to cap-independent translation switch in breast cancer
Braunstein, Steve; Karpisheva, Ksenia; Pola, Carolina; Goldberg, Judith; Hochman, Tsivia; Yee, Herman; Cangiarella, Joan; Arju, Rezina; Formenti, Silvia C; Schneider, Robert J
2007 Nov 9;28(3):501-512, Molecular cell
Translational regulation is critical in cancer development and progression. Translation sustains tumor growth and development of a tumor vasculature, a process known as angiogenesis, which is activated by hypoxia. Here we first demonstrate that a majority of large advanced breast cancers overexpress translation regulatory protein 4E-BP1 and initiation factor eIF4G. Using model animal and cell studies, we then show that overexpressed 4E-BP1 and eIF4G orchestrate a hypoxia-activated switch from cap-dependent to cap-independent mRNA translation that promotes increased tumor angiogenesis and growth at the level of selective mRNA translation. Elevated levels of 4E-BP1 trigger hypoxia inhibition of cap-dependent mRNA translation at high-oxygen levels and, with eIF4G, increase selective translation of mRNAs containing internal ribosome entry sites (IRESs) that include key proangiogenic, hypoxia, and survival mRNAs. The switch from cap-dependent to cap-independent mRNA translation facilitates tumor angiogenesis and hypoxia responses in animal models
— id: 75671, year: 2007, vol: 28, page: 501, stat: Journal Article,

Para-aminobenzoic acid (PABA) enhances the anti-tumor activity of radiotherapy (RT) in the human glioblastoma multiforme T98G cell line both in-vitro and in-vivo
Buckley, Michael T.; Gittleman, Alicia E.; Devitt, Mary L.; Ng, Bruce; Dewyngaert, J. Keith; Brooks, Peter; Formenti, Silvia C.; Liebes, Leonard
2007 ;48(6):738-738, Proceedings (American Association for Cancer Research)
— id: 109225, year: 2007, vol: 48, page: 738, stat: Journal Article,

IMRT treatment for locally advanced non-small cell lung cancer achieves low levels of pulmonary irradiation including the low-dose volume, V 5 Gy, along with low levels of esophageal and cardiac irradiation
Chandra, A; Mitchell, JD; McCarthy, A; Chachoua, A; Jozsef, G; DeWyngaert, K; Pass, HI; Formenti, S
2007 JAN ;69(3):S523-S523, International journal of radiation oncology biology physics
— id: 87195, year: 2007, vol: 69, page: S523, stat: Journal Article,

Disruption of endothelial cell interactions with the novel HU177 cryptic collagen epitope inhibits angiogenesis
Cretu, Alexandra; Roth, Jennifer M; Caunt, Maresa; Akalu, Abebe; Policarpio, Desiree; Formenti, Silvia; Gagne, Paul; Liebes, Leonard; Brooks, Peter C
2007 May 15;13(10):3068-3078, Clinical cancer research
PURPOSE: The importance of cellular communication with the extracellular matrix in regulating cellular invasion is well established. Selective disruption of communication links between cells and the local microenvironment by specifically targeting non-cellular matrix-immobilized cryptic extracellular matrix epitopes may represent an effective new clinical approach to limit tumor-associated angiogenesis. Therefore, we sought to determine whether the HU177 cryptic collagen epitope plays a functional role in regulating angiogenesis in vivo. EXPERIMENTAL DESIGN: We examined the expression and characterized the HU177 cryptic collagen epitope in vitro and in vivo using immunohistochemistry and ELISA. We examined potential mechanisms by which this cryptic collagen epitope may regulate angiogenesis using in vitro cell adhesion, migration, proliferation, and biochemical assays. Finally, we examined the whether blocking cellular interactions with the HU177 cryptic epitope plays a role in angiogenesis and tumor growth in vivo using the chick embryo model. RESULTS: The HU177 cryptic epitope was selectively exposed within tumor blood vessel extracellular matrix, whereas little was associated with quiescent vessels. An antibody directed to this cryptic site selectively inhibited endothelial cell adhesion, migration, and proliferation on denatured collagen type IV and induced increased levels of cyclin-dependent kinase inhibitor p27(KIP1). Systemic administration of mAb HU177 inhibited cytokine- and tumor-induced angiogenesis in vivo. CONCLUSIONS: We provide evidence for a new functional cryptic regulatory element within collagen IV that regulates tumor angiogenesis. These findings suggest a novel and highly selective approach for regulating angiogenesis by targeting a non-cellular cryptic collagen epitope
— id: 73410, year: 2007, vol: 13, page: 3068, stat: Journal Article,

Exploiting breast cancer cells stress response to ionizing radiation to improve the effectiveness of immunotherapy
Demaria, S; Wang, B; Badura, M; Matsumura, S; Kawashima, N; Cameron, T; Dustin, M; Schneider, RJ; Formenti, SC
2007 JAN ;69(3):S597-S597, International journal of radiation oncology biology physics
— id: 87199, year: 2007, vol: 69, page: S597, stat: Journal Article,

Sensors of ionizing radiation effects on the immunological microenvironment of cancer
Demaria, Sandra; Formenti, Silva C
2007 Nov-Dec;83(11-12):819-825, International journal of radiation biology
PURPOSE: When cancer develops in an immunocompetent host it represents the result of a successful deception of the immune system as to the nature of the danger and the type of response needed to reject the neoplastic tissue. We will briefly review some of the recently emerged evidence that irradiation of the tumor and its microenvironment can induce essential molecular signals required for an effective response of the immune system to the tumor. CONCLUSIONS: The subversion of a highly organized tissue architecture is a hallmark of cancer, and results in uneven distribution of oxygen and nutrients, interstitial pressure gradients and areas of patchy necrosis and inflammation. In this microenvironment, cancer cells that carry mutations favoring survival rather than cell death in response to stress find a selection advantage. Importantly, the signals derived from the disruption of orderly physiology within tissues are also what the immune system has evolved to respond to. The type of response is tuned to be adequate to the cause of the disruption. An infectious organism will carry or elicit from the involved tissue a number of 'danger signals' leading to development of cell mediated and humoral responses to both eliminating the invader and preventing future infections. In contrast, a simple wound will call for a repair response. The sensors of the type of damage are complex molecular interactions between the damaged organ and cells of the innate and adaptive immune system. Progress in the identification of these interactions elucidates which pathways are specifically altered in cancer. It also provides a novel understanding of the radiation-induced effects on tumor immunogenicity. We propose that specific radiation-induced effects could be successfully exploited to improve the effectiveness of immunotherapy
— id: 76330, year: 2007, vol: 83, page: 819, stat: Journal Article,

Accelerated intensity-modulated radiotherapy to breast in prone position: dosimetric results
DeWyngaert, J Keith; Jozsef, Gabor; Mitchell, James; Rosenstein, Barry; Formenti, Silvia C
2007 Jul 15;68(4):1251-1259, International journal of radiation oncology biology physics
PURPOSE: To report the physics and dosimetry results of a trial of accelerated intensity-modulated radiotherapy to the whole breast with a concomitant boost to the tumor bed in patients treated in the prone position. METHODS AND MATERIALS: Patients underwent computed tomography planning and treatment in the prone position on a dedicated treatment platform. The platform has an open aperture on the side to allow for the index breast to fall away from the chest wall. Noncontrast computed tomography images were acquired at 2.5- or 3.75-mm-thick intervals, from the level of the mandible to below the diaphragm. A dose of 40.5 Gy was delivered to the entire breast at 2.7-Gy fractions in 15 fractions. An additional dose of 0.5 Gy was delivered as a concomitant boost to the lumpectomy site, with a 1-cm margin, using inverse planning, for a total dose of 48 Gy in 15 fractions. No more than 10% of the heart and lung volume was allowed to receive >18 and >20 Gy, respectively. RESULTS: Between September 2003 and August 2005, 91 patients were enrolled in the study. The median volume of heart that received > or =18 Gy was 0.5%, with a maximal value of 4.7%. The median volume of ipsilateral lung that received > or =20 Gy was 0.8%, with a maximum of 7.2%. CONCLUSION: This technique for whole breast radiotherapy is feasible and enables an accelerated regimen in the prone position while sparing the lung and heart
— id: 73387, year: 2007, vol: 68, page: 1251, stat: Journal Article,

Prospective trial of individual optimal positioning (prone versus supine) for whole breast radiotherapy: results of 194 patients
Formenti, SC; Guth, AA; Axelrod, DM; Goldberg, JD; DeWyngaert, JK
2007 DEC ;106(1):S194-S194, Breast cancer research & treatment
— id: 75805, year: 2007, vol: 106, page: S194, stat: Journal Article,

Prospective trial of individual optimal positioning (Prone versus supine) for whole breast radiotherapy: Results of the first 168 patients
Formenti, SC; Parhar, PK; Goldberg, JD; DeWyngaert, JK
2007 JAN ;69(3):S74-S74, International journal of radiation oncology biology physics
— id: 87192, year: 2007, vol: 69, page: S74, stat: Journal Article,

External-beam-based partial breast irradiation
Formenti, Silvia C
2007 Jun;4(6):326-327, Nature clinical practice. Oncology
— id: 72994, year: 2007, vol: 4, page: 326, stat: Journal Article,

Phase I-II trial of prone accelerated intensity modulated radiation therapy to the breast to optimally spare normal tissue
Formenti, Silvia C; Gidea-Addeo, Daniela; Goldberg, Judith D; Roses, Daniel F; Guth, Amber; Rosenstein, Barry S; DeWyngaert, Keith J
2007 Jun 1;25(16):2236-2242, Journal of clinical oncology
PURPOSE: To report the clinical feasibility of a trial of accelerated whole-breast intensity modulated radiotherapy, with the patient in prone position, optimally to spare the heart and lung. PATIENTS AND METHODS: Patients with stages I or II breast cancer, excised by breast conserving surgery with negative margins, were eligible for this institutional review board-approved prospective trial. Computed tomography simulation was performed with the patient prone on a dedicated breast board, in the exact position used for treatment. A dose of 40.5 Gy, delivered at 2.7 Gy in 15 fractions, was prescribed to the index breast with an additional concomitant boost of 0.5 Gy delivered to the tumor bed, for a total dose of 48 Gy to the lumpectomy site. Physics constraints consisted of limiting 5% of the heart volume to receive > or = 18 Gy and < or = 10% of the ipsilateral lung volume to receive > or = 20 Gy. RESULTS: Between September 2003 and August 2005, 91 patients were enrolled on the study. Median length of follow-up was 12 months (range, 1 to 28 months). In all patients the technique was feasible and heart and lung sparing was achieved as prescribed by the protocol. Acute toxicities consisting mostly of reversible grades 1-2 skin dermatitis (67%) and fatigue (18%) occurred in 75 patients. One patient sustained a regional recurrence rapidly followed by distant metastases. CONCLUSION: Accelerated whole breast intensity modulated radiotherapy in the prone position is feasible and it permits a drastic reduction in the volume of lung and heart tissue exposed to significant radiation.
— id: 72870, year: 2007, vol: 25, page: 2236, stat: Journal Article,

Possession of ATM sequence variants as predictor for late normal tissue responses in breast cancer patients treated with radiotherapy
Ho, Alice Y; Fan, Grace; Atencio, David P; Green, Sheryl; Formenti, Silvia C; Haffty, Bruce G; Iyengar, Preetha; Bernstein, Jonine L; Stock, Richard G; Cesaretti, Jamie A; Rosenstein, Barry S
2007 Nov 1;69(3):677-684, International journal of radiation oncology biology physics
PURPOSE: The ATM gene product is a central component of cell cycle regulation and genomic surveillance. We hypothesized that DNA sequence alterations in ATM predict for adverse effects after external beam radiotherapy for early breast cancer. METHODS AND MATERIALS: A total of 131 patients with a minimum of 2 years follow-up who had undergone breast-conserving surgery and adjuvant radiotherapy were screened for sequence alterations in ATM using DNA from blood lymphocytes. Genetic variants were identified using denaturing high performance liquid chromatography. The Radiation Therapy Oncology Group late morbidity scoring schemes for skin and subcutaneous tissues were applied to quantify the radiation-induced effects. RESULTS: Of the 131 patients, 51 possessed ATM sequence alterations located within exons or in short intron regions flanking each exon that encompass putative splice site regions. Of these 51 patients, 21 (41%) exhibited a minimum of a Grade 2 late radiation response. In contrast, of the 80 patients without an ATM sequence variation, only 18 (23%) had radiation-induced adverse responses, for an odds ratio of 2.4 (95% confidence interval, 1.1-5.2). Fifteen patients were heterozygous for the G-->A polymorphism at nucleotide 5557, which causes substitution of asparagine for aspartic acid at position 1853 of the ATM protein. Of these 15 patients, 8 (53%) exhibited a Grade 2-4 late response compared with 31 (27%) of the 116 patients without this alteration, for an odds ratio of 3.1 (95% confidence interval, 1.1-9.4). CONCLUSION: Sequence variants located in the ATM gene, in particular the 5557 G-->A polymorphism, may predict for late adverse radiation responses in breast cancer patients
— id: 93555, year: 2007, vol: 69, page: 677, stat: Journal Article,

Single-dose radiation stimulates induction of stromal derived factor-1 expression and endothelial cell migration independently of hypoxia activation
Lerman, O; Grieves, M; Levine, J; Schneider, R; Formenti, S
2007 JAN ;69(3):S592-S593, International journal of radiation oncology biology physics
— id: 87197, year: 2007, vol: 69, page: S592, stat: Journal Article,

Noscapine enhances tumor radioresponse in the GL261 glioma model: Implications for glioma therapy
Lukyanov, Y; Newcomb, EW; Aionso-Basanta, M; Schnee, T; Shao, Y; McBride, WH; Formenti, SC
2007 JAN ;69(3):S591-S592, International journal of radiation oncology biology physics
— id: 87196, year: 2007, vol: 69, page: S591, stat: Journal Article,

Interfraction setup variability for prone breast radiotherapy
Mitchell, JD; DeWyngaert, JK; Formenti, SC
2007 JAN ;69(3):S710-S711, International journal of radiation oncology biology physics
— id: 87200, year: 2007, vol: 69, page: S710, stat: Journal Article,

The integrin-TGF beta axis: Inhibition of integrin alpha v beta 6 prevents radiation-induced lung fibrosis
Munger, J; Cheng, SK; Puthawala, K; Hadjiangelis, N; Jacoby, S; Formenti, SC
2007 JAN ;69(3):S1-S1, International journal of radiation oncology biology physics
— id: 87190, year: 2007, vol: 69, page: S1, stat: Journal Article,

Pre-clinical assessment of CD137 (4-1BB)-mediated co-stimulation in combination with whole brain radiation therapy in the 61,261 glioma model
Newcomb, EW; Demaria, S; Lukyanov, Y; Schnee, T; Kawashima, N; Formenti, SC
2007 JAN ;69(3):S152-S152, International journal of radiation oncology biology physics
— id: 87194, year: 2007, vol: 69, page: S152, stat: Journal Article,

Vitronectin in the tumor microenvironment promotes breast cancer cell proliferation and elevated protein synthesis despite hypoxia by integrin alpha v beta 3 activation of the mTOR/4E-BP1 pathway
Pola, C; Formenti, SC; Schneider, RJ
2007 DEC ;106(1):S162-S162, Breast cancer research & treatment
— id: 75804, year: 2007, vol: 106, page: S162, stat: Journal Article,

Phase I study of bi-weekly paclitasel and definitive radiation in androgen ablated locally advanced prostate cancer
Sanfilippo, NJ; Taneja, SS; Chachoua, A; Lepor, H; Formenti, SC
2007 JAN ;69(3):S112-S113, International journal of radiation oncology biology physics
— id: 87193, year: 2007, vol: 69, page: S112, stat: Journal Article,

Elevated levels of translation initiation factor eIF4G suppresses Radiation(IR)-induced autophagy and cell death
Schneider, RJ; Braunstein, S; Badura, M; Formenti, SC
2007 JAN ;69(3):S593-S593, International journal of radiation oncology biology physics
— id: 87198, year: 2007, vol: 69, page: S593, stat: Journal Article,

Assessment of interobserver and intraobserver variability in measuring compliance of the breast with the tissue compliance meter
Wernicke, AG; Parhar, P; Baer, L; Rasca, M; Goldbeg, J; Formenti, SC
2007 JAN ;69(3):S237-S238, International journal of radiation oncology biology physics
— id: 98156, year: 2007, vol: 69, page: S237, stat: Journal Article,

ATM sequence variants and risk of radiation-induced subcutaneous fibrosis after postmastectomy radiotherapy
Andreassen, Christian N; Overgaard, Jens; Alsner, Jan; Overgaard, Marie; Herskind, Carsten; Cesaretti, Jamie A; Atencio, David P; Green, Sheryl; Formenti, Silvia C; Stock, Richard G; Rosenstein, Barry S
2006 Mar 1;64(3):776-783, International journal of radiation oncology biology physics
PURPOSE: To examine the hypothesis that women who are carriers of genetic alterations in the ATM gene are more likely to develop subcutaneous fibrosis after radiotherapy for treatment of breast cancer compared with patients who do not possess DNA sequence variations in this gene. METHODS AND MATERIALS: DNA samples isolated from fibroblast cell lines established from 41 women treated with postmastectomy radiotherapy for breast cancer were screened for genetic variants in ATM using denaturing high-performance liquid chromatography (DHPLC). A minimum follow-up of 2 years enabled analysis of late effects to generate dose-response curves and to estimate the dose that resulted in a 50% incidence of Grade 3 fibrosis (ED50). RESULTS: A total of 26 genetic alterations in the expressed portions of the ATM gene, or within 10 bases of each exon in regions encompassing putative splice sites, were detected in 22 patients. The ED50 (95% confidence interval) of 60.2 (55.7-65.1) Gy calculated for patients without a sequence variation did not differ significantly from the ED50 of 58.4 (54.0-63.1) Gy for the group of patients with any ATM sequence abnormality. The ED50 of 53.7 (50.2-57.5) Gy for those patients who were either homozygous or heterozygous for the G-->A polymorphism at nucleotide 5557, which results in substitution of asparagine for aspartic acid at position 1853 of the ATM protein, was substantially lower than the ED50 of 60.8 (57.0-64.8) Gy for patients not carriers of this sequence alteration. This resulted in an enhancement ratio (ratio of the ED50 values) of 1.13 (1.05-1.22), which was significantly greater than unity. CONCLUSION: The results of this study suggest an association between the ATM codon 1853 Asn/Asp and Asn/Asn genotypes with the development of Grade 3 fibrosis in breast cancer patients treated with radiotherapy
— id: 64380, year: 2006, vol: 64, page: 776, stat: Journal Article,

Ionizing radiation regulates protein synthesis through two novel ATM-independent and ATM-dependent pathways involving mTOR and translation regulator, 4E-BP1
Braunstein, S; Badura, M; Xi, Q; Formenti, SC; Schneider, RJ
2006 FEB ;66(3):S71-S71, International journal of radiation oncology biology physics
— id: 70752, year: 2006, vol: 66, page: S71, stat: Journal Article,

Para-aminobenzoic acid (PABA) enhances responses to low and high dose rate radiotherapy (RT) in glioblastoma cell lines
Buckley, Michael T.; Kang, Josephine; Brooks, Peter; Devitt, M. L.; Dewyngaert, J. Keith; Ng, Bruce; Formenti, Silvia C.; Liebes, Leonard; Vlachaki, Maria T.
2006 ;47(6):139-139, Proceedings (American Association for Cancer Research)
— id: 109226, year: 2006, vol: 47, page: 139, stat: Journal Article,

Hypoxia inhibits protein synthesis through a 4E-BP1 and elongation factor 2 kinase pathway controlled by mTOR and uncoupled in breast cancer cells
Connolly, Eileen; Braunstein, Steve; Formenti, Silvia; Schneider, Robert J
2006 May;26(10):3955-3965, Molecular & cellular biology
Hypoxia is a state of low oxygen availability that limits tumor growth. The mechanism of protein synthesis inhibition by hypoxia and its circumvention by transformation are not well understood. Hypoxic breast epithelial cells are shown to downregulate protein synthesis by inhibition of the kinase mTOR, which suppresses mRNA translation through a novel mechanism mitigated in transformed cells: disruption of proteasome-targeted degradation of eukaryotic elongation factor 2 (eEF2) kinase and activation of the regulatory protein 4E-BP1. In transformed breast epithelial cells under hypoxia, the mTOR and S6 kinases are constitutively activated and the mTOR negative regulator tuberous sclerosis complex 2 (TSC2) protein fails to function. Gene silencing of 4E-BP1 and eEF2 kinase or TSC2 confers resistance to hypoxia inhibition of protein synthesis in immortalized breast epithelial cells. Breast cancer cells therefore acquire resistance to hypoxia by uncoupling oxygen-responsive signaling pathways from mTOR function, eliminating inhibition of protein synthesis mediated by 4E-BP1 and eEF2
— id: 64480, year: 2006, vol: 26, page: 3955, stat: Journal Article,

Intrafraction organ motion in breast radiation therapy: A comparison of prone versus supine patient positioning
DeWyngaert, JK; Mitchell, JD; Alonso-Basanta, M; Formenti, SC
2006 FEB ;66(3):S177-S178, International journal of radiation oncology biology physics
— id: 70754, year: 2006, vol: 66, page: S177, stat: Journal Article,

Intra-fraction organ motion in breast radiotherapy: a comparison of prone versus supine patient positioning
DeWyngaert, JK; Mitchell, JD; Formenti, SC
2006 FEB ;100(2):S201-S202, Breast cancer research & treatment
— id: 71012, year: 2006, vol: 100, page: S201, stat: Journal Article,

Genetic variants as predictors of late adverse radiotherapy effects in breast cancer patients
Fan, G; Burri, R; Racsa, M; Green, S; Formenti, SC; Kuten, A; Ozahin, M; Haffty, BG; Stock, RG; Rosenstein, BS
2006 FEB ;66(3):S211-S211, International journal of radiation oncology biology physics
— id: 70756, year: 2006, vol: 66, page: S211, stat: Journal Article,

Accelerated prone breast radiotherapy: preliminary results of a prospective intensity modulated radiotherapy (IMRT) trial
Formenti, SC; Gidea-Addeo, D; Wernicke, AG; Goldberg, JD; Amber, GA; DeWyngaert, JK
2006 FEB ;100(2):S198-S199, Breast cancer research & treatment
— id: 71010, year: 2006, vol: 100, page: S198, stat: Journal Article,

Optimal normal tissue sparing by prone breast radiotherapy: preliminary results of a prospective trial to establish the individual optimal positioning for breast radiotherapy
Formenti, SC; Parhar, PK; Racsa-Alamgir, M; Constantine, C; Wernicke, AG; DeWyngaert, JK
2006 FEB ;100(2):S201-S201, Breast cancer research & treatment
— id: 71011, year: 2006, vol: 100, page: S201, stat: Journal Article,

NYU 01-51: Phase I-II trial of hypofractionated whole breast radiation therapy for ductal carcinoma in situ (DCIS)
Formenti, SC; Wernicke, AG; Gittleman, AE; Rosenstein, BS; DeWyngaert, JK
2006 FEB ;66(3):S178-S178, International journal of radiation oncology biology physics
— id: 70755, year: 2006, vol: 66, page: S178, stat: Journal Article,

External beam partial-breast radiotherapy: crucial differences between NYU 00-23 and RTOG 0319: in regard to Vicini et al. (Int J Radiat Oncol Biol Phys 2005;63:1531-1537)
Formenti, Silvia C; Wernicke, A Gabriella; DeWyngaert, J Keith
2006 Oct 1;66(2):630-630, International journal of radiation oncology biology physics
— id: 93557, year: 2006, vol: 66, page: 630, stat: Journal Article,

Very-low-dose radiation is associated with improved MMP-9-dependent reperfusion in ischemic mouse hindlimbs
Glaser, J; Hobeika, M; Qiao, JR; Devitt, ML; Formenti, S; Gagne, E; Brooks, P; Gagne, P
2006 SEP ;203(3):S106-S107, Journal of the American College of Surgeons
— id: 69820, year: 2006, vol: 203, page: S106, stat: Journal Article,

Genetic Predictors of Adverse Radiotherapy Effects: The Gene-PARE project
Ho, Alice Y; Atencio, David P; Peters, Sheila; Stock, Richard G; Formenti, Silvia C; Cesaretti, Jamie A; Green, Sheryl; Haffty, Bruce; Drumea, Karen; Leitzin, Larisa; Kuten, Abraham; Azria, David; Ozsahin, Mahmut; Overgaard, Jens; Andreassen, Christian N; Trop, Cynthia S; Park, Janelle; Rosenstein, Barry S
2006 Jul 1;65(3):646-655, International journal of radiation oncology biology physics
Purpose: The development of adverse effects resulting from the radiotherapy of cancer limits the use of this treatment modality. The validation of a test capable of predicting which patients would be most likely to develop adverse responses to radiation treatment, based on the possession of specific genetic variants, would therefore be of value. The purpose of the Genetic Predictors of Adverse Radiotherapy Effects (Gene-PARE) project is to help achieve this goal. Methods and Materials: A continuously expanding biorepository has been created consisting of frozen lymphocytes and DNA isolated from patients treated with radiotherapy. In conjunction with this biorepository, a database is maintained with detailed clinical information pertaining to diagnosis, treatment, and outcome. The DNA samples are screened using denaturing high performance liquid chromatography (DHPLC) and the Surveyor nuclease assay for variants in ATM, TGFB1, XRCC1, XRCC3, SOD2, and hHR21. It is anticipated that additional genes that control the biologic response to radiation will be screened in future work. Results: Evidence has been obtained that possession of variants in genes, the products of which play a role in radiation response, is predictive for the development of adverse effects after radiotherapy. Conclusions: It is anticipated that the Gene-PARE project will yield information that will allow radiation oncologists to use genetic data to optimize treatment on an individual basis
— id: 64378, year: 2006, vol: 65, page: 646, stat: Journal Article,

A translationally controlled angiogenic switch in locally advanced breast cancer
Karpisheva, K; Braunstein, S; Goldberg, J; Singh, B; Pola, C; Formenti, SC; Schneider, RJ
2006 FEB ;100(2):S11-S11, Breast cancer research & treatment
— id: 71005, year: 2006, vol: 100, page: S11, stat: Journal Article,

The combination of ionizing radiation and peripheral vaccination produces long-term survival of mice bearing established invasive GL261 gliomas
Newcomb, Elizabeth W; Demaria, Sandra; Lukyanov, Yevgeniy; Shao, Yongzhao; Schnee, Tona; Kawashima, Noriko; Lan, Li; Dewyngaert, J Keith; Zagzag, David; McBride, William H; Formenti, Silvia C
2006 Aug 1;12(15):4730-4737, Clinical cancer research
PURPOSE: High-grade glioma treatment includes ionizing radiation therapy. The high invasiveness of glioma cells precludes their eradication and is responsible for the dismal prognosis. Recently, we reported the down-regulation of MHC class I (MHC-I) products in invading tumor cells in human and mouse GL261 gliomas. Here, we tested the hypothesis that whole-brain radiotherapy (WBRT) up-regulates MHC-I expression on GL261 tumors and enhances the effectiveness of immunotherapy. EXPERIMENTAL DESIGN: MHC-I molecule expression on GL261 cells was analyzed in vitro and in vivo by flow cytometry and immunohistochemistry, respectively. To test the response of established GL261 gliomas to treatment, mice with measurable (at CT imaging) brain tumors were randomly assigned to four groups receiving (a) no treatment, (b) WBRT in two fractions of 4 Gy, (c) vaccination with irradiated GL261 cells secreting granulocyte-macrophage colony-stimulating factor, or (d) WBRT and vaccination. Endpoints were tumor response and survival. RESULTS: An ionizing radiation dose of 4 Gy maximally up-regulated MHC-I molecules on GL261 cells in vitro. In vivo, WBRT induced the expression of the beta2-microglobulin light chain subunit of the MHC class I complex on glioma cells invading normal brain and increased CD4+ and CD8+ T cell infiltration. However, the survival advantage obtained with WBRT or vaccination alone was minimal. In contrast, WBRT in combination with vaccination increased long-term survival to 40% to 80%, compared with 0% to 10% in the other groups (P < 0.002). Surviving animals showed antitumor immunity by rejecting challenge tumors. CONCLUSION: Ionizing radiation can be successfully combined with peripheral vaccination for the treatment of established high-grade gliomas
— id: 67436, year: 2006, vol: 12, page: 4730, stat: Journal Article,

Radiation Sensitivity of GL261 Murine Glioma Model and Enhanced Radiation Response by Flavopiridol
Newcomb, Elizabeth W; Lymberis, Stella C; Lukyanov, Yevgeniy; Shao, Yongzhao; Schnee, Tona; Devitt, Marylou; Rosenstein, Barry S; Zagzag, David; Formenti, Silvia C
2006 Jan;5(1):93-99, Cell cycle
Response of a solid tumor to radiation treatment depends, in part, on the intrinsic radiosensitivity of tumor cells, the proliferation rate of tumor cells between radiation treatments and the hypoxic state of the tumor cells. A successful radiosensitizing agent would target S-phase cells and hypoxia. Recently, we demonstrated the anti-tumor effects of flavopiridol in the GL261 murine glioma model might involve 1) recruitment of tumor cells to S-phase (Newcomb et al Cell Cycle 2004; 3:230-234) and 2) an anti-angiogenic effect on the tumor vasculature by downregulation of hypoxia-inducible factor -1alpha (HIF-1alpha) (Newcomb et al Neuro-Oncology 2005; 7:225-235). Given that flavopiridol has demonstrated radiosensitizing activity in several murine tumor models, we tested whether it would enhance the response of GL261 tumors to radiation. In the present study, we evaluated the intrinsic radiation sensitivity of the GL261 glioma model using the tumor control/cure dose of radiation assay (TCD(50)). We found that a single dose of 65 Gy (CI 57.1-73.1) was required to cure 50% of the tumors locally. Using the tumor growth delay assay, fractionated radiation (5 fractions of 5 Gy over 10 days) combined with flavopiridol (5 mg/kg) given three times weekly for 3 cycles produced a significant growth delay. Our results indicate that the GL261 murine glioma model mimics the radioresistance encountered in human gliomas, and thus should prove useful in identifying promising new investigational radiosensitizers for use in the treatment of glioma patients
— id: 62423, year: 2006, vol: 5, page: 93, stat: Journal Article,

Preliminary results of NYU 05-181, a prospective trial to establish the individual optimal positioning for breast radiotherapy
Parhar, PK; Constantine, C; Racsa-Alamgir, M; Wernicke, G; Fenton, M; DeWyngaert, K; Formenti, SC
2006 FEB ;66(3):S177-S177, International journal of radiation oncology biology physics
— id: 70753, year: 2006, vol: 66, page: S177, stat: Journal Article,

Inhibition of experimental metastasis by targeting the HUIV26 cryptic epitope in collagen
Roth, Jennifer M; Caunt, Maresa; Cretu, Alexandra; Akalu, Abebe; Policarpio, Desiree; Li, Xiaolu; Gagne, Paul; Formenti, Silvia; Brooks, Peter C
2006 May;168(5):1576-1586, American journal of pathology
Metastasis from the primary tumor to distant sites involves an array of molecules that function in an integrated manner. Proteolytic remodeling and subsequent tumor cell interactions with the extracellular matrix regulate tumor invasion. In previous studies, we have identified a cryptic epitope (HUIV26) that is specifically exposed after alterations in the triple helical structure of type IV collagen. Exposure of this cryptic epitope plays a fundamental role in the regulation of angiogenesis in vivo. However, little is known concerning the ability of tumor cells to interact with this cryptic site or whether this site regulates tumor cell metastasis in vivo. In this regard, many of the same cellular processes that regulate angiogenesis also contribute to tumor metastasis. Here we provide evidence that tumor cells such as B16F10 melanoma interact with denatured collagen type IV in part by recognizing the HUIV26 cryptic site. Systemic administration of a HUIV26 monoclonal antibody inhibited experimental metastasis of B16F10 melanoma in vivo. Taken together, our findings suggest that tumor cell interactions with the HUIV26 cryptic epitope play an important role in regulating experimental metastasis and that this cryptic element may represent a therapeutic target for controlling the spread of tumor cells to distant sites
— id: 67002, year: 2006, vol: 168, page: 1576, stat: Journal Article,

Over-expression of initiation factor eIF4G typifies inflammatory breast cancer and is crucial for tumor growth, VEGF expression and angiogenesis
Silvera, D; Formenti, SC; Schneider, RJ
2006 FEB ;100(2):S168-S168, Breast cancer research & treatment
— id: 71007, year: 2006, vol: 100, page: S168, stat: Journal Article,

Results of surgical resection for progression of brain metastases previously treated by gamma knife radiosurgery
Truong, Minh T; St Clair, Eric G; Donahue, Bernadine R; Rush, Stephen C; Miller, Douglas C; Formenti, Silvia C; Knopp, Edmond A; Han, Kerry; Golfinos, John G
2006 Jul;59(1):86-97, Neurosurgery
OBJECTIVE: To determine treatment outcome after surgical resection for progressive brain metastases after gamma knife radiosurgery (GKR) and to explore the role of dynamic contrast agent-enhanced perfusion magnetic resonance imaging (MRI) and proton spectroscopic MRI studies (MRS/P) in predicting pathological findings. METHODS: Between 1997 and 2002, 32 patients underwent surgical resection for suspected progression of brain metastases from a cohort of 245 patients with brain metastases treated with GKR. Postradiosurgery MRI surveillance was performed at 6 and 12 weeks, and then every 12 weeks after GKR. In some cases, additional MRI scanning with spectroscopy or perfusion (MRS/P) was used to aid differentiation of radiation change from tumor progression. The decision to perform neurosurgical resection was based on MRI or clinical evidence of lesion progression among patients with a Karnofsky performance score of 60 or more and absent or stable systemic disease. RESULTS: Thirteen percent (32 out of 245) of patients and 6% (38 out of 611) of lesions required surgical resection after GKR. The median time from GKR to surgical resection was 8.6 months (range, 1.7-27.1 mo). The 6-, 12-, and 24-month actuarial survival from time of GKR was 97, 78, and 47% for the resected patients and 65, 40, and 19% for the nonresected patients (P < 0.0001). The two-year survival rate of patients requiring two resections after GKR was 100% compared with 39% for patients undergoing one resection (P = 0.02). The median survival of resected patients was 27.2 months (range, 7.0-72.5 mo) from the diagnosis of brain metastases, 19.9 months (range, 5.0-60.7 mo) from GKR, and 8.9 months (range, 0.2-53.1 mo) from surgical resection. Tumor was found in 90% of resected specimens and necrosis alone in 10%. MRS/P studies were performed in 15 resected patients. Overall, MRS/P predicted tumor in 11 lesions, confirmed pathologically in nine lesions, and necrosis alone was found in two. The MRS/P predicted necrosis alone in three, whereas pathology revealed viable tumor in two and necrosis in one lesion. CONCLUSION: Surgical intervention of progressive brain metastases after GKR in selected patients leads to a meaningful improvement in survival rates. Further studies are necessary to determine the role of MRS/P in the postradiosurgery surveillance of brain metastases
— id: 67932, year: 2006, vol: 59, page: 86, stat: Journal Article,

CXCR6 and CXCL16 are expressed by breast cancer cells and may play a dual role in tumor progression
Wang, B; Badura, M; He, C; Cameron, T; Dustin, M; Formenti, SC; Schneider, RJ; Demaria, S
2006 FEB ;100(2):S299-S299, Breast cancer research & treatment
— id: 71013, year: 2006, vol: 100, page: S299, stat: Journal Article,

External beam partial breast irradiation following breast-conserving surgery: Preliminary results of cosmetic outcome of NYU 00-23
Wernicke, AG; Gidea-Addeo, D; Magnolfi, C; Fenton-Kerimian, M; Goldberg, J; Formenti, SC
2006 FEB ;66(3):S32-S32, International journal of radiation oncology biology physics
— id: 70751, year: 2006, vol: 66, page: S32, stat: Journal Article,

The vitamin-like dietary supplement para-aminobenzoic acid enhances the antitumor activity of ionizing radiation
Xavier, Sandhya; Macdonald, Shannon; Roth, Jennifer; Caunt, Maresa; Akalu, Abebe; Morais, Danielle; Buckley, Michael T; Liebes, Leonard; Formenti, Silvia C; Brooks, Peter C
2006 Jun 1;65(2):517-527, International journal of radiation oncology biology physics
PURPOSE: To determine whether para-aminobenzoic acid (PABA) alters the sensitivity of tumor cells to ionizing radiation in vitro and in vivo. METHODS AND MATERIALS: Cellular proliferation was assessed by WST-1 assays. The effects of PABA and radiation on tumor growth were examined with chick embryo and murine models. Real-time reverse transcriptase-polymerase chain reaction and Western blotting were used to quantify p21CIP1 and CDC25A levels. RESULTS: Para-aminobenzoic acid enhanced (by 50%) the growth inhibitory activity of radiation on B16F10 cells, whereas it had no effect on melanocytes. Para-aminobenzoic acid enhanced (50-80%) the antitumor activity of radiation on B16F10 and 4T1 tumors in vivo. The combination of PABA and radiation therapy increased tumor apoptosis. Treatment of tumor cells with PABA increased expression of CDC25A and decreased levels of p21CIP1. CONCLUSIONS: Our findings suggest that PABA might represent a compound capable of enhancing the antitumor activity of ionizing radiation by a mechanism involving altered expression of proteins known to regulate cell cycle arrest
— id: 64379, year: 2006, vol: 65, page: 517, stat: Journal Article,

Selective inhibition of tumor cell interactions with a cryptic collagen epitope enhances the anti-tumor activity of ionizing radiation
Akalu, A; Xavier, S; Roth, J; DeWyngaert, K; Formenti, S; Brooks, P
2005 NOV 16 ;63(2):S119-S119, International journal of radiation oncology biology physics
— id: 58989, year: 2005, vol: 63, page: S119, stat: Journal Article,

Regulation of endogenous angiogenesis inhibitor TSP-1 by integrin alpha v ss 3
Akalu, Abebe; Policarpio, Desiree; Cretu, Alexandra; Roth, Jennifer; Formenti, Silvia; Brooks, Peter
2005 ;46(6):1100-1101, Proceedings (American Association for Cancer Research)
— id: 109227, year: 2005, vol: 46, page: 1100, stat: Journal Article,

Dosimetric comparisons of supine versus prone radiation: Implications on normal tissue toxicity
Alonso-Basanta, M; MacDonald, S; Lymberis, S; Ko, J; DeRouen, M; Jozsef, G; DeWyngaert, JK; Formenti, SC
2005 NOV 16 ;63(2):S182-S183, International journal of radiation oncology biology physics
— id: 58992, year: 2005, vol: 63, page: S182, stat: Journal Article,

A phase I study of continuous intravenous infusion (CIV) low-dose topotecan (T) combined with thoracic radiotherapy (RT)
Chandra, A; Chang, R; Steinfeld, A; Chachoua, A; Muggia, F; Formenti, S; Hochster, H
2005 ;63(2):2314-2314, International journal of radiation oncology biology physics
— id: 109248, year: 2005, vol: 63, page: 2314, stat: Journal Article,

Inhibition of TGF-beta activation by integrin-beta6 is protective against acute radiation skin injury
Cheng, S; Jacoby, S; Grant, K; Xavier, S; Munger, J; Formenti, S
2005 NOV 16 ;63(2):S461-S462, International journal of radiation oncology biology physics
— id: 58996, year: 2005, vol: 63, page: S461, stat: Journal Article,

The combination of ionizing radiation and peripheral vaccination produces long-term survival of mice bearing invasive GL261 glioma
Demaria, S; Newcomb, EW; Zagzag, D; Lukyanov, E; Schnee, T; Kawashima, N; Devitt, M; Formenti, SC
2005 NOV 16 ;63(2):S171-S171, International journal of radiation oncology biology physics
— id: 58991, year: 2005, vol: 63, page: S171, stat: Journal Article,

Combining radiotherapy and immunotherapy: a revived partnership
Demaria, Sandra; Bhardwaj, Nina; McBride, William H; Formenti, Silvia C
2005 Nov 1;63(3):655-666, International journal of radiation oncology biology physics
Ionizing radiation therapy (RT) is an important local modality for the treatment of cancer. The current rationale for its use is based largely on the ability of RT to kill the cancer cells by a direct cytotoxic effect. Nevertheless, considerable evidence indicates that RT effects extend beyond the mere elimination of the more radiosensitive fraction of cancer cells present within a tumor at the time of radiation exposure. For instance, a large body of evidence is accumulating on the ability of RT to modify the tumor microenvironment and generate inflammation. This might have far-reaching consequences regarding the response of a patient to treatment, especially if radiation-induced tumor cell kill were to translate into the generation of effective antitumor immunity. Although much remains to be learned about how radiation can impact tumor immunogenicity, data from preclinical studies provide the proof of principle that different immunotherapeutic strategies can be combined with RT to enhance antitumor effects. Conversely, RT could be a useful tool to combine with immunotherapy. This article will briefly summarize what is known about the impact of RT on tumor immunity, including tumor-associated antigens, antigen-presenting cells, and effector mechanisms. In addition, the experimental evidence supporting the contention that RT can be used as a tool to induce antitumor immunity is discussed, and a new approach to radioimmunotherapy of cancer is proposed
— id: 62122, year: 2005, vol: 63, page: 655, stat: Journal Article,

Ethical, legal, and social issues related to genomics and cancer research: the impending crisis
Ellerin, Bruce E; Schneider, Robert J; Stern, Arnold; Toniolo, Paolo G; Formenti, Silvia C
2005 Nov;2(11):919-926, Journal of the American College of Radiology : JACR
Cancer research is a multibillion-dollar enterprise validated by the clinical trial process and increasingly defined by genomics. The continued success of the endeavor depends on the smooth functioning of the clinical trial system, which in turn depends on human subject participation. Yet human subject participation can exist only in an atmosphere of trust between research participants and research sponsors, and the advent of genomics has raised a multitude of ethical, legal, and social issues that threaten this trust. The authors examine 6 of these issues: (1) informed consent; (2) privacy, confidentiality, and family disclosure dilemmas; (3) property rights in genomic discoveries; (4) individual and institutional conflicts of interest; (5) insurance and employment issues; and (6) litigation under the federal False Claims Act. The authors conclude that failure to resolve these issues may lead to a sufficient impairment of trust in genomics-based clinical trials on the part of potential research participants that the clinical trial system may implode for lack of willing participants, thus threatening the future of cancer research
— id: 72043, year: 2005, vol: 2, page: 919, stat: Journal Article,

Beta-catenin induces a population of radio-resistant alveolar stem/progenitors that progress to form hormone-independent breast tumors in mice
Formenti, SC; Hiremath, M; Yang, A; Demaria, S; Cowin, P
2005 ;63(2):2396-2396, International journal of radiation oncology biology physics
— id: 109265, year: 2005, vol: 63, page: 2396, stat: Journal Article,

Antibody to avb6 integrin prevents radiation-induced lung fibrosis
Formenti, SC; Jacoby, S; Grant, K; Horan, G; Weinreb; Devitt, M; Munger, J
2005 ;63(2):2408-2408, International journal of radiation oncology biology physics
— id: 109266, year: 2005, vol: 63, page: 2408, stat: Journal Article,

NYU 03-30: Accelerated IMRT with concomitant boost after breast conservation surgery. preliminary clinical results in 70 patients
Formenti, SC; Mitchell, J; Goldberg, J; Magnolfi, C; Rosenstein, B; Remon, S; DeWyngaert, K
2005 ;63(2):S181-S182, International journal of radiation oncology biology physics
— id: 109264, year: 2005, vol: 63, page: S181, stat: Journal Article,

Hypo-Fractionated Conformal Radiation Therapy to the Tumor Bed After Segmental Mastectomy
Formenti, Silvia C
[Ft. Belvoir, VA] : Ft. Belvoir Defense Technical Information Center, 2005,
This IDEA grant proposal tested the feasibility of a regimen of conformal hypo-fractionated radiotherapy (5 fractions in 2 weeks) directed to the original tumor bed with margins in a selected subset of post-menopausal women with breast cancer with a very low risk for local recurrence elsewhere in the breast. The relevance of this approach consists of the fact that if proven equivalent in efficacy it would be more patient-friendly (30 fractions over 6 weeks) convenient and economical. This final report demonstrated feasibility in all 63 patients accrued to the trial, with minimal acute side effects. Among the 53 patients with at least 6 months follow-up late effects were limited to the rare occurrence of modest fibrosis and teleangectasia. With a median follow up of 24 months, in none of the patients breast cancer has recurred. Prone partial breast radiotherapy, delivered by an external beam simple technique over 5 fractions was feasible and very well tolerated. These results need to be confirmed in a larger cohort of patients, ideally in a multi-institutional setting
— id: 2128, year: 2005, vol: , page: , stat: ,

In regard to Kao et al.: concomitant radiation therapy and paclitaxel for unresectable locally advanced breast cancer: results from two consecutive phase I/II trials (Int J Radiat Oncol Biol Phys 2005;61:1045-1053)
Formenti, Silvia C
2005 Nov 15;63(4):1275-1276, International journal of radiation oncology biology physics
— id: 64381, year: 2005, vol: 63, page: 1275, stat: Journal Article,

ATM sequence variants as predictors for late normal tissue responses in breast cancer patients treated with radiotherapy
Ho, AY; Atencio, DP; Fan, G; Green, S; Formenti, SC; Haffty, BG; Bernstein, JL; Iyengar, P; Stock, RG; Cesaretti, JA; Rosenstein, BS
2005 NOV 16 ;63(2):S457-S458, International journal of radiation oncology biology physics
— id: 58995, year: 2005, vol: 63, page: S457, stat: Journal Article,

ATM sequence variants as predictors for adverse radiation responses in breast cancer patients
Ho, AY; Atencio, DP; Fan, G; Green, S; Formenti, SC; Haffty, BG; Bernstein, JL; Stock, RG; Cesaretti, JA; Rosenstein, BS
2005 ;94(2):S178-S178, Breast cancer research & treatment
— id: 109267, year: 2005, vol: 94, page: S178, stat: Journal Article,

Accelerated concomitant boost in raditation treatment
Lief EP; DeWyngaert JK; Lymberis SC; Formenti SC
Intensity modulated radiation therapy : a clinical perspective Hamilton ON : BC Decker, 2005,
— id: 5314, year: 2005, vol: , page: 398, stat: Chapter,

Equivalent biological effective dose (BEDeq) modeling of tumor control probability in Partial Breast Irradiation
Lymberis, SC; Rosenstein, BS; Jozsef, G; Formenti, SC; DeWyngaert, J
2005 ;63(2):2037-2037, International journal of radiation oncology biology physics
— id: 109268, year: 2005, vol: 63, page: 2037, stat: Journal Article,

Impact of tissue heterogeneity corrections on tumor and normal structure dosimetry in nasopharyngeal carcinoma treated with intensity modulated radiation therapy
Sanfilippo, N; Hitchen, C; Tran, T; DeLacure, M; Kutler, D; Formenti, S
2005 NOV 16 ;63(2):S374-S375, International journal of radiation oncology biology physics
— id: 58994, year: 2005, vol: 63, page: S374, stat: Journal Article,

Ionizing radiation controls protein synthesis through a novel akt-independent pathway involving regulation of mTOR and 4E-BP1 stability
Schneider, R; Braunstein, S; Xi, Q; Formenti, S
2005 NOV 16 ;63(2):S146-S146, International journal of radiation oncology biology physics
— id: 58990, year: 2005, vol: 63, page: S146, stat: Journal Article,

Potentiation of radiation-induced growth inhibition of non-small cell lung cancer by borteomib and para-aminobenzoid acid
Vlachaki, Maria T.; Cho, Jennie J.; Buckley, Mike T.; Brooks, Peter; Devitt, Mary L.; Formenti, Silvia C.; Hoschster, Howard; Liebes, Leonard F.
2005 ;46(6):341-341, Proceedings (American Association for Cancer Research)
— id: 109228, year: 2005, vol: 46, page: 341, stat: Journal Article,

Treatment of locally advanced breast cancer
Volm M; Formenti SC
Breast cancer Philadelphia PA : Elsevier Churchill Livingstone, 2005,
— id: 5313, year: 2005, vol: , page: ?, stat: Chapter,

Potentiation of radiation induced growth inhibition of glioma cells with combinations of nM levels of bortezomib and hypericin
Buckley, Michael; Ng, Bruce; Zolotarov, Alex; Devitt, Mary Lou; Formenti, Silvia; Liebes, Leonard
2004 ;45(6):1126-1126, Proceedings (American Association for Cancer Research)
— id: 109229, year: 2004, vol: 45, page: 1126, stat: Journal Article,

Combination of local radiation with targeted immunomodulation improves systemic tumor control
Demaria, Sandra; Kawashima, Noriko; Devitt, Mary Louise; Babb, James S.; Allison, James P.; Formenti, Silvia C.
2004 ;45(6):505-505, Proceedings (American Association for Cancer Research)
— id: 109230, year: 2004, vol: 45, page: 505, stat: Journal Article,

Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated
Demaria, Sandra; Ng, Bruce; Devitt, Mary Louise; Babb, James S; Kawashima, Noriko; Liebes, Leonard; Formenti, Silvia C
2004 Mar 1;58(3):862-870, International journal of radiation oncology biology physics
PURPOSE: Ionizing radiation can reduce tumor growth outside the field of radiation, known as the abscopal effect. Although it has been reported in multiple malignancies, the abscopal effect remains a rare and poorly understood event. Ionizing radiation generates inflammatory signals and, in principle, could provide both tumor-specific antigens from dying cells and maturation stimuli that are necessary for dendritic cells' activation of tumor-specific T cells. We therefore tested the hypothesis that the abscopal effect elicited by radiation is immune mediated. This was directly tested by enhancing the number of available dendritic cells using the growth factor Flt3-Ligand (Flt3-L). METHODS AND MATERIALS: Mice bearing a syngeneic mammary carcinoma, 67NR, in both flanks were treated with Flt3-L daily for 10 days after local radiation therapy (RT) to only 1 of the 2 tumors at a single dose of 2 or 6 Gy. The second nonirradiated tumor was used as indicator of the abscopal effect. Data were analyzed using repeated measures regression. RESULTS: RT alone led to growth delay exclusively of the irradiated 67NR tumor, as expected. Surprisingly, growth of the nonirradiated tumor was also impaired by the combination of RT and Flt3-L. As control, Flt3-L had no effect without RT. Importantly, the abscopal effect was shown to be tumor specific, because growth of a nonirradiated A20 lymphoma in the same mice containing a treated 67NR tumor was not affected. Moreover, no growth delay of nonirradiated 67NR tumors was observed when T cell deficient (nude) mice were treated with RT plus Flt3-L. CONCLUSIONS: These results demonstrate that the abscopal effect is in part immune mediated and that T cells are required to mediate distant tumor inhibition induced by radiation
— id: 42588, year: 2004, vol: 58, page: 862, stat: Journal Article,

Prone accelerated partial breast irradiation (five fractions) after breast conservation therapy with heart and lung sparing
Formenti, SC; Goldberg, J; Rosenstein, B; Dewyngaert, K
2004 ;22(14):93S-93S #870, Journal of clinical oncology
— id: 109269, year: 2004, vol: 22, page: 93S, stat: Journal Article,

Hypo-Fractionated Conformal Radiation Therapy to the Tumor Bed After Segmental Mastectomy
Formenti, Silvia C
[Ft. Belvoir, VA] : Ft. Belvoir Defense Technical Information Center, 2004,
This trial tests a regimen of prone conformal hypo-fractionated radiotherapy directed to the original tumor bed with margins in a selected subset of post-menopausal women with breast cancer with a very low risk for local recurrence elsewhere in the breast. After planning CT is conducted in the prone position, the breast tissue and tumor bed are contoured on a 3D planning system and a 2 cm margin added to determine the planning treatment volume (PTV) . A plan is generated to treat the PTV with six Gy per fraction are delivered to the 95% isodose surface in 5 fractions over ten days weeks to a total dose of 30 Gy. Fifty-three of the 99 patients planned to accrue to the study have completed treatment and the results have been reported at the ASTRO 2003 meeting and 2004 American Radium Society meeting. All patients tolerated treatment very well. DVH varied based on the position of the original tumor bed and the size of the breast. In most cases it was possible to successfully plan and treat a quadrant of the breast without exceeding 50% of the dose to 50% of the breast volume. Longer follow up is necessary to assess efficacy and cosmetic results
— id: 2127, year: 2004, vol: , page: , stat: ,

Flavopiridol as a radiation sensitizer using the preclinical GL261 glioma animal model
Lymberis, Stella C.; Lukyanov, Yevgeniy; Schnee, Tona; Ng, Bruce; Devitt, Mary Louise; Formenti, Silvia C.; Newcomb, Elizabeth W.
2004 ;45(6):311-311, Proceedings (American Association for Cancer Research)
— id: 109231, year: 2004, vol: 45, page: 311, stat: Journal Article,

Pharmacogenomics and breast cancer
Lymberis, Stella C; Parhar, Preeti K; Katsoulakis, Evangelia; Formenti, Silvia C
2004 Jan;5(1):31-55, Pharmacogenomics
Germline variants can be used to study breast cancer susceptibility as well as the variable response to both drug and radiation therapy used in the treatment of breast cancer. In addition to germline high-penetrance mutations important in familial and hereditary breast cancer, a substantial component of breast cancer risk can be attributed to the combined effect of many low-risk germline polymorphisms involved in relevant pathways like those of DNA repair, adhesion, carcinogen and estrogen metabolism. Additionally, the identification of sequence variants in genes involved in response to chemotherapy and radiation treatment, has created the opportunity to apply genomics to individualized treatment. The continued insight into the molecular pathways involved in drug and radiation response has enabled progress in tailoring therapies in such a way as to both maximize efficacy and minimize toxicity. Polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters and drug targets can be used to predict toxicity and response to pharmacologic agents used in breast cancer treatment. Similarly, germline variants in genes involved in DNA repair, radiation-induced fibrosis and reactive oxygen species may be used to predict response to radiation therapy. As a result, pharmacogenomics is rapidly evolving to affect the entire spectrum of breast cancer management, influencing both prevention and treatment choices
— id: 44867, year: 2004, vol: 5, page: 31, stat: Journal Article,

Para-amino benzoic acid (PABA), a radiation and chemotherapy sensitizer
MacDonald, SM; Caunt, M; Brooks, PC; Formenti, SC
2004 ;60(1):S352-S352 #2022, International journal of radiation oncology biology physics
— id: 109270, year: 2004, vol: 60, page: S352, stat: Journal Article,

The integrin alpha v beta 6-knockout mouse is protected from radiation-induced lung fibrosis: Implications for the clinic
Munger, J; Hadjiangelis, N; Emmanuel, B; Devitt, M; Formenti, SC
2004 ;60(1):S327-S327 #1120, International journal of radiation oncology biology physics
— id: 109271, year: 2004, vol: 60, page: S327, stat: Journal Article,

Biologic comparison of partial breast irradiation protocols
Rosenstein, Barry S; Lymberis, Stella C; Formenti, Silvia C
2004 Dec 1;60(5):1393-1404, International journal of radiation oncology biology physics
PURPOSE: To analyze the dose/fractionation schedules currently used in ongoing clinical trials of partial breast irradiation (PBI) by comparing their biologically effective dose (BED) values to those of three standard whole breast protocols commonly used after segmental mastectomy in the treatment of breast cancer. METHODS AND MATERIALS: The BED equation derived from the linear-quadratic model for radiation-induced cell killing was used to calculate the BEDs for three commonly used whole breast radiotherapy regimens, in addition to a variety of external beam radiotherapy, as well as high-dose-rate and low-dose-rate brachytherapy, PBI protocols. RESULTS: The BED values of most PBI protocols resulted in tumor control BEDs roughly equivalent to a 50-Gy standard treatment, but consistently lower than the BEDs for regimens in which the tumor bed receives a total dose of either 60 Gy or 66 Gy. The BED values calculated for the acute radiation responses of erythema and desquamation were nearly all lower for the PBI schedules, and the late-response BEDs for most PBI regimens were in a similar range to the BEDs for the standard treatments. CONCLUSION: Biologically effective dose modeling raises the concern that inadequate doses might be delivered by PBI to ensure optimal in-field tumor control
— id: 64382, year: 2004, vol: 60, page: 1393, stat: Journal Article,

Overexpression of a critical target of rapamycin, translation regulatory protein 4E-BP1, is largely restricted to locally advanced breast and prostrate cancers and is lost with tumor invasiveness
Schneider, Robert J.; Kharpasheva, Ksen; Formenti, Silvia; Braunstein, Steven; Connolly, Eileen
2004 ;45(6):1158-1159, Proceedings (American Association for Cancer Research)
— id: 109232, year: 2004, vol: 45, page: 1158, stat: Journal Article,

Para-Amino Benzoic Acid (PABA) modulates expression and stability of CDC25A in tumor cells and enhances radiosensitivity in vitro and in vivo
Xavier, S; Roth, J; Caunt, M; Akalu, A; Rodriguez, D; MacDonald, S; Devitt, M; Rosenstein, B; Formenti, SC; Brooks, PC
2004 ;60(1):S360-S361 #2038, International journal of radiation oncology biology physics
— id: 109272, year: 2004, vol: 60, page: S360, stat: Journal Article,

Combination of local radiation with CTLA4 blockade: a new approach to the immunotherapy of breast cancer
Demaria S; Kawashima N; Devitt M; Allison JP; Formenti SC
2003 Oct 1;57(2 Suppl):S259-S259, International journal of radiation oncology biology physics
— id: 39082, year: 2003, vol: 57, page: S259, stat: Journal Article,

Hypo-Fractionated Conformal Radiation Therapy to the Tumor Bed After Segmental Mastectomy
Formenti, Silvia C; Roses, Daniel; Harris, Matthew; Shapiro, Richard; Guth, Amber
[Ft. Belvoir, VA] : Ft. Belvoir Defense Technical Information Center, 2003,
The current trial tests a regimen of conformal hypo-fractionated radiotherapy (5 fractions) directed to the original tumor bed with margins in a selected subset of post- menopausal women with breast cancer with a very low risk for local recurrence elsewhere in the breast. We are currently reporting the feasibility results and DVH analysis of the first 4% patients accrued. After planning CT is conducted in the prone position the breast tissue and tumor bed are contoured on a 3D planning system and a 2 cm margin added to determine the PTV. A plan is generated to treat the PTV to 90% of the prescription dose. Six Gy per fraction are delivered to the 95% isodose surface in 5 fractions over ten days weeks to a total dose of 30 Gy. All patients appeared to tolerate treatment very well. DVH varied based on the position of the original tumor bed and the size of the breast. In most cases it was possible to successfully plan and treat a quadrant of the breast with parallel opposed tangent fields without exceeding 50% of the dose to 50% of the breast volume. We continue accrual as planned, to a total of 99 patients
— id: 2130, year: 2003, vol: , page: , stat: ,

Preoperative twice-weekly paclitaxel with concurrent radiation therapy followed by surgery and postoperative doxorubicin-based chemotherapy in locally advanced breast cancer: a phase I/II trial
Formenti, Silvia C; Volm, Matthew; Skinner, Kristin A; Spicer, Darcy; Cohen, Deidre; Perez, Edith; Bettini, Anna C; Groshen, Susan; Gee, Conway; Florentine, Barbara; Press, Michael; Danenberg, Peter; Muggia, Franco
2003 Mar 1;21(5):864-870, Journal of clinical oncology
PURPOSE: Preoperative chemotherapy is the conventional primary treatment in locally advanced breast cancer (LABC). We investigated the safety and efficacy of primary twice-weekly paclitaxel and concurrent radiation (RT) before modified radical mastectomy followed by adjuvant doxorubicin-based chemotherapy. PATIENTS AND METHODS: Stage IIB (T3N0) to III LABC patients were eligible. Primary chemoradiation consisted of paclitaxel, 30 mg/m(2) delivered intravenously for 1 hour twice weekly for a total of 8 to 10 weeks, and concurrent RT (45 Gy at 1.8 Gy/fraction). Modified radical mastectomy was performed at least 2 weeks after completion of chemoradiation or on recovery of skin toxicity. Postoperatively, patients who responded to paclitaxel and RT received four cycles of doxorubicin/paclitaxel, whereas patients who did not respond received doxorubicin/cytoxan. RESULTS: Forty-four patients were accrued. Toxicity from paclitaxel/RT included grade 3 skin desquamation (7%), hypersensitivity (2%), and stomatitis (2%). Postsurgery complications occurred in six patients (14%). The only grade 4 toxicity of postmastectomy chemotherapy was hematologic (10%). Grade 3 toxicities were leukopenia (24%), infection (22%), peripheral neuropathy (17%), arthralgia and pain (17%), stomatitis (12%), fatigue (10%), esophagitis (5%), and nausea (2%). Overall clinical response rate to preoperative paclitaxel and RT was 91%. Thirty-four percent of patients achieved a pathologic response in the mastectomy specimen: 16% pathologic complete responses (clearance of invasive cancer in the breast and axillary contents) and 18% pathologic partial responses (< 10 residual microscopic foci of invasive breast cancer). CONCLUSION: Twice-weekly paclitaxel with concurrent RT is a feasible and effective primary treatment for LABC. Future studies should compare primary chemoradiation to chemotherapy in LABC
— id: 34943, year: 2003, vol: 21, page: 864, stat: Journal Article,

IMRT for concomitant boost to the tumor bed for breast cancer radiation therapy
Lief EP; DeWyngaert J; Formenti SC
2003 Oct 1;57(2 Suppl):S366-S366, International journal of radiation oncology biology physics
— id: 38107, year: 2003, vol: 57, page: S366, stat: Journal Article,

Comparable B16 melanoma growth inhibition observed by either administration of HU177 monoclonal antibody or by ionizing radiation therapy
Lymberis, Stella C.; Rodriquez, Dorothy Y.; Roth, Jennifer Mary; Devitt, Mary Louise; Brooks, Peter C.; Formenti, Silvia C.
2003 ;44(6):888-888, Proceedings (American Association for Cancer Research)
— id: 109233, year: 2003, vol: 44, page: 888, stat: Journal Article,

Coating of culture plates with collagen increases the in vitro effects of both PS-341 and ionizing radiation (RT)
Ng, Bruce; Snell, Jamaal; Brooks, Peter; Liebes, Leonard; Formenti, Silvia
2003 ;44(6):247-247, Proceedings (American Association for Cancer Research)
— id: 109234, year: 2003, vol: 44, page: 247, stat: Journal Article,

Hypo-fractionated partial breast radiation after breast-conserving surgery: preliminary clinical results and dose volume histogram (DVH) analysis
Truong M; Rosenstein B; Goldberg J; Cho C; DeWyngaert KJ; Formenti SC
2003 Oct 1;57(2 Suppl):S367-S368, International journal of radiation oncology biology physics
— id: 39081, year: 2003, vol: 57, page: S367, stat: Journal Article,

Novel approaches to postoperative radiation therapy as part of breast-conserving therapy for early-stage breast cancer
Truong, Minh Tam; Hirsch, Ariel E; Formenti, Silvia C
2003 Oct;4(4):253-263, Clinical breast cancer
Breast-conserving therapy (BCT) consists of segmental mastectomy followed by postoperative radiation therapy (RT) to the whole breast. At least 6 prospective randomized trials have proven the equivalence of BCT to mastectomy. However, BCT remains underused and, most importantly, a sizable proportion of patients with invasive breast cancer fail to complete the recommended protocol of breast preservation by omitting postoperative RT. The inconvenience of complying with the standard 6-week radiation regimen, which includes approximately 30 daily visits, at least partially explains this lack of adherence. New clinical studies have generated preliminary evidence that more convenient, shorter radiation regimens might reveal equivalence to the current standard. Moreover, the availability of modern technology to deliver and target ionizing radiation by improving homogeneity of radiation dose has made it possible to safely explore the use of greater radiation doses per fraction. Finally, currently ongoing research trials will enable the identification of specific subsets of patients who are likely to be safely treated by partial-breast radiation (instead of radiation to the whole breast) with more accelerated regimens. This article reviews the available data and the current ongoing research on novel RT techniques and fractionation schedules in BCT for early-stage breast cancer
— id: 44868, year: 2003, vol: 4, page: 253, stat: Journal Article,

High rate of positive anti-tissue transglutaminase antibodies in chronic liver disease. Role of liver decompensation and of the antigen source
Vecchi, M; Folli, C; Donato, M F; Formenti, S; Arosio, E; de Franchis, R
2003 Jan;38(1):50-54, Scandinavian journal of gastroenterology
BACKGROUND: Since the recognition of tissue transglutaminase (tTG) as the target antigen of anti-endomysium antibodies, several ELISA assays using either guinea pig or human recombinant tTG have been developed. The aim of the study was to compare the behaviour of anti-tTG and anti-endomysium antibodies assays in coeliacs and in patients with chronic liver disease. METHODS: 34 patients (24 women, 34.9 +/- 12.5 years) with coeliac disease and 41 with chronic liver disease (14 women, 57 +/- 11.2 years), including 19 cirrhotics, were evaluated for anti-endomysium antibodies by indirect immunofluorescence and for anti-tTG IgA antibodies by ELISA, using guinea pig liver or human recombinant transglutaminase. RESULTS: The prevalences of anti-tTG and anti-endomysium antibodies were 100% in patients with coeliac disease at diagnosis, 75% and 64.3% in patients on a gluten-free diet. All liver disease patients were negative for anti-endomysium antibodies, while 11 (26.8%) were positive for anti-tTG. All these patients had liver cirrhosis and represented 57.9% of all cirrhotics. The presence of anti-tTG was associated with higher Child-Pugh scores. The use of human transglutaminase determined a reduction in the rate of positive results; however, the rate of positive anti-tTG was still 17.1% in all liver disease patients and 31.6% in cirrhotics. CONCLUSIONS: Our data confirm that anti-tTG have a similar sensitivity compared with anti-endomysium antibodies assay in coeliacs. However, a high prevalence of positive anti-tTG results is observed in cirrhotic patients, even when human recombinant tTG is used. The high prevalence of positive results among cirrhotic patients is associated with more advanced liver disease
— id: 44869, year: 2003, vol: 38, page: 50, stat: Journal Article,

P7 antigen expression in human breast cancer
Yang, Xiaowei; Groshen, Susan; Formenti, Silvia C; Davidson, Nancy E; Press, Michael F
2003 Jan;9(1):201-206, Clinical cancer research
PURPOSE: Evaluate p7 expression in human breast cancer and determine whether chemotherapy and radiation therapy effect a change in p7 expression. Experimental Design: Using a p7-specific monoclonal antibody with immunohistochemistry and Western immunoblot analyses to assess p7 expression in archival, frozen breast cancer specimens both before and after therapy. RESULTS: A novel 7 kDa protein (p7), originally identified in multidrug-resistant ovarian and breast cancer cell lines, was found to be expressed in 21 of 64 (32%) primary, unselected human breast cancer specimens by immunohistochemistry with the use of a p7-specific monoclonal antibody, 1D7. P7 was observed in malignant cells but not in other types of cells in the breast tissue. Western blot analysis confirmed the 7 kDa polypeptide in p7-positive breast carcinomas identified by immunohistochemistry. P7 expression was significantly associated with breast cancers having distant metastasis and/or local recurrence (P = 0.027, Fisher's exact test). In addition, p7 expression was significantly increased in post-treatment breast cancer biopsy specimens compared with pretreatment breast cancer biopsy specimens in patients with locally advanced breast cancer after 5-fluorouracil chemotherapy and radiation therapy [2 of 15 (13%) pretreatment breast cancers compared with 8 of 15 (53%) post-treatment breast cancers; P = 0.016, McNemar's test]. CONCLUSIONS: These findings demonstrate that expression of p7 is associated with malignant tumor cells in primary breast cancers, especially those showing recurrent or metastatic disease. Its specific association with the malignant phenotype suggests it may have potential for novel target-based therapies. The markedly increased expression in patients with locally advanced disease after neoadjuvant therapy suggests a role for p7 in treatment outcome
— id: 34944, year: 2003, vol: 9, page: 201, stat: Journal Article,

Dose-dependent effects of ionizing radiation on angiogenesis and matrix metalloproteinases
Brooks, Peter C.; Broek, Dan; Roth, Jennifer; Louise Devitt, Mary; Lymberis, Stella; DeWyngaert, Keith; Formenti, Silvia Chiara
2002 ;43(6):1149-1150, Proceedings (American Association for Cancer Research)
— id: 109235, year: 2002, vol: 43, page: 1149, stat: Journal Article,

Ionizing radiation modulates the exposure of the HUIV26 cryptic epitope within collagen type IV during angiogenesis
Brooks, Peter C; Roth, Jennifer M; Lymberis, Stella C; DeWyngaert, Keith; Broek, Daniel; Formenti, Silvia C
2002 Nov 15;54(4):1194-1201, International journal of radiation oncology biology physics
PURPOSE: The majority of the research on the biologic effects of ionizing radiation has focused on the impact of radiation on cells in terms of gene expression, DNA damage, and cytotoxicity. In comparison, little information is available concerning the direct effects of radiation on the extracellular microenvironment, specifically the extracellular matrix and its main component, collagen. We have developed a series of monoclonal antibodies that bind to cryptic epitopes of collagen Type IV that are differentially exposed during matrix remodeling and are key mediators of angiogenesis. We have hypothesized that ionizing radiation might affect the process of angiogenesis through a direct effect on the extracellular matrix and specifically on collagen Type IV. METHODS AND MATERIALS: Angiogenesis was induced in a chick chorioallantoic membrane (CAM) model; 24 h later, a single-dose treatment with ionizing radiation (0.5, 5, and 20 cGy) was administered. Angiogenesis was assessed, and the exposure of two cryptic regulatory epitopes within collagen Type IV (HUI77 and HUIV26) was studied in vitro by solid-phase ELISA and in vivo by immunofluorescence staining. RESULTS: A dose-dependent reduction of angiogenesis with maximum inhibition (85%-90%) occurring at 20 cGy was demonstrated in the CAM model. Exposure of the cryptic HUIV26 site, an angiogenesis control element, was inhibited both in vitro and in vivo by the same radiation dose, whereas little if any change was observed for the HUI77 cryptic epitope. CONCLUSIONS: A dose-dependent alteration of the functional exposure of the HUIV26 cryptic epitope is induced by radiation in vitro and in the CAM model in vivo. This radiation-induced change in protein structure and function may contribute to the inhibitory effects of ionizing radiation on new blood vessel growth and warrants further studies in other models
— id: 150851, year: 2002, vol: 54, page: 1194, stat: Journal Article,

Chemotherapy can induce apoptosis of cancer cells coupled to the production of maturation signals for dendritic cells
Demaria, Sandra; Ng, Bruce; Santori, Fabio R.; Liebes, Leonard; Vukmanovic, Stanislav; Formenti, Silvia C.
2002 ;43(6):678-678, Proceedings (American Association for Cancer Research)
— id: 109236, year: 2002, vol: 43, page: 678, stat: Journal Article,

Combined modality therapy in locally advanced breast cancer
Formenti SC; Volm M
Chemoradiation in cancer therapy Totowa NJ : Huamana, 2002,
— id: 5315, year: 2002, vol: , page: 237, stat: Chapter,

Pre-clinical studies of concomitant PS-341 and ionizing radiation therapy: local and systemic anti-tumor effects
Formenti, S; Demaria, S; Liebes, L; Ng, B; Devitt, M; Babbs, J; Muggia, F
2002 NOV ;38(4):34-A256, European journal of cancer
— id: 98237, year: 2002, vol: 38, page: 34, stat: Journal Article,

T1 stage breast cancer: adjuvant hypofractionated conformal radiation therapy to tumor bed in selected postmenopausal breast cancer patients--pilot feasibility study
Formenti, Silvia C; Rosenstein, Barry; Skinner, Kristin A; Jozsef, Gabor
2002 Jan;222(1):171-178, Radiology
PURPOSE: To explore the feasibility of a short course of hypofractionated conformal radiation therapy to the tumor bed as part of a breast preservation protocol in postmenopausal patients with nonpalpable pT1N0 stage breast cancer. MATERIALS AND METHODS: The tumor bed was imaged at computed tomography (CT) in the prone position on a dedicated table. The same table and position were used for treatment with a 4-MV linear accelerator. The planning target volume was the tumor bed plus a 1-2-cm margin defined at postmastectomy CT. A regimen of five fractions was tested in this pilot dose study. Cosmesis was assessed by patients and physicians before treatment and 36 months after treatment. RESULTS: Ten consecutive patients who were eligible for the study were assigned to one of three dose-per-fraction regimens; nine were treatable with the proposed technique on the basis of CT findings. Patients received five fractions over 10 days (total dose range, 25-30 Gy): Three received 5.0 Gy per fraction; four, 5.5 Gy; and two, 6.0 Gy. At minimum follow-up of 36 months (range, 36-53 months), all patients were alive and disease free with good to excellent cosmesis. CONCLUSION: Hypofractionated conformal breast radiation therapy is feasible. Further studies are warranted
— id: 34946, year: 2002, vol: 222, page: 171, stat: Journal Article,

Hypo-Fractionated Conformal Radiation Therapy to the Tumor Bed After Segmental Mastectomy
Formenti, Silvia C; Roses, Daniel; Harris, Matthew; Shapiro, Richard; Guth, Amber
[Ft. Belvoir, VA] : Ft. Belvoir Defense Technical Information Center, 2002,
The current trial tests a regimen of conformal hypo-fractionated radiotherapy (5 fractions) directed to the original tumor bed with margins in a selected subset of post- menopausal women with breast cancer with a very low risk for local recurrence elsewhere in the breast. We are currently reporting the feasibility results and DVN analysis of the first 29 patients accrued. After planning CT is conducted in the prone position the breast tissue and tumor bed are contoured on a 3D planning system and a 2 cm margin added to determine the PTV. A plan is generated to treat the PTV to 90% of the prescription dose. Six Gy per fraction are delivered to the 95 isodose surface in 5 fractions over ten days weeks to a total dose of 30 Gy. All patients appeared to tolerate treatment very well. DVH varied based on the position of the original tumor bed and the size of the breast. In most cases it was possible to successfully plan and treat a quadrant of the breast with parallel opposed tangent fields without exceeding 50% of the dose to 50% of the breast volume. We continue accrual as planned, to a total of 99 patients
— id: 2129, year: 2002, vol: , page: , stat: ,

Low HER2/neu gene expression is associated with pathological response to concurrent paclitaxel and radiation therapy in locally advanced breast cancer
Formenti, Silvia C; Spicer, Darcy; Skinner, Kristin; Cohen, Deidre; Groshen, Susan; Bettini, Anna; Naritoku, Wesley; Press, Michael; Salonga, Dennis; Tsao-Wei, Denice; Danenberg, Kathy; Danenberg, Peter
2002 Feb 1;52(2):397-405, International journal of radiation oncology biology physics
PURPOSE: The objective of this study was twofold: first, to identify patients with locally advanced breast cancer (LABC) who will achieve a pathological response to a preoperative regimen of concurrent paclitaxel and radiation; and second, to explore associations between molecular markers from the original tumors and pathological response. METHODS AND MATERIALS: Patients with previously untreated LABC were eligible to receive a regimen of preoperative concurrent paclitaxel, 30 mg/m(2) twice a week for a total of 8 weeks, and radiation delivered Weeks 2--6, 45 Gy at 1.8 Gy per fraction to the breast, ipsilateral axilla, and supraclavicular nodes. At mastectomy, pathologic findings were classified as pathological complete response (pCR) = no residual invasive cells in the breast and axillary contents; pathological partial response (pPR) = presence of < or = 10 microscopic foci of invasive cells; no pathological response (pNR) = pathological persistence of tumor. For each patient, pretreatment breast cancer biopsies were prospectively analyzed by immunohistochemistry (IHC) for estrogen and progesterone (ER/PR) hormonal receptors, HER2/neu and p53 overexpression. Estrogen receptor (ER), HER2/neu, metablastin, beta-tubulin III and IV, microtubule-associated protein-4 (MAP-4), bcl-2, bax, and cyclooxygenase-2 (COX-2) gene expression were measured using real-time quantitative polymerase chain reaction (PCR). RESULTS: A total of 36 patients had pretreatment biopsies and were evaluable for the analysis of the association of molecular markers with pathological response. Pathological response in the mastectomy specimen was achieved in 12 of these 36 patients (33%). Only HER2/neu and ER gene expression were found to be significantly associated with the extent of pathological response to the regimen, i.e., tumors with low HER2/neu gene expression and negative estrogen receptors were more likely to respond to the tested regimen (p = 0.009 and p = 0.006, respectively). Conversely, p53 protein expression measured by IHC did not appear to be associated with pathological response (p = 0.67). CONCLUSION: Further studies in LABC should assess whether patient selection for treatment based on the original tumor molecular characteristics could affect their chance to achieve a pathological response
— id: 34945, year: 2002, vol: 52, page: 397, stat: Journal Article,

Diagnostic x-rays and risk of epithelial ovarian carcinoma in Jews
Harlap, Susan; Olson, Sara H; Barakat, Richard R; Caputo, Thomas A; Forment, Silvia; Jacobs, Allan J; Nakraseive, Christine; Xue, Xiaonan
2002 Aug;12(6):426-434, Annals of epidemiology
PURPOSE: To test the hypothesis that there would be ethnic differences in susceptibility to ionizing radiation from diagnostic x-rays. METHODS: In a hospital-based study we compared reports of diagnostic x-rays to the lower abdomen and pelvis in incident cases of epithelial ovarian carcinoma (N = 161), community controls (N = 156) and convenience controls (N = 87). RESULTS: Thirty-nine per cent of cases and 31% of controls recalled x-rays more than 10 years before; 27% of cases and 14% of controls reported four Jewish grandparents. Comparing the cases with community controls, the odds ratio (95% confidence interval) for Jews versus non-Jews among women reporting no x-rays was 1.02 (0.37-2.79); among women reporting x-rays the estimate for Jews was 8.91 (2.00-39.6). Consistent results were seen with inclusion of convenience controls. Jewish cases reported an excess of pelvic diagnostic x-rays from age 20 onward and an excess of barium enemas and pyelograms. CONCLUSIONS: These preliminary findings require confirmation in other studies. They suggest that the known excess risk of this carcinoma in Jews might be associated with exposure to x-rays and add to a previous observation of an altered susceptibility to ionizing radiation in Jews. If confirmed, they would suggest a need for continued vigilance to evaluate the risks and benefits of diagnostic x-rays in individuals, regardless of ethnic origin, who might carry mutations in DNA repair genes
— id: 39611, year: 2002, vol: 12, page: 426, stat: Journal Article,

Current data with liposomal anthracyclines in metatastic breast cancer
Muggia F; Formenti SC; Volm M
2002 Aug;1(1):11-14, Current trends in anthracyclines
— id: 109306, year: 2002, vol: 1, page: 11, stat: Journal Article,

Effect of ionizing radiation with paclitaxel, docetaxel and PS-341 in melanoma cells
Ng, Bruce; Fong, Dean; Devitt, Mary Louise; Formenti, Silvia; Liebes, Leonard
2002 ;43(6):480-480, Proceedings (American Association for Cancer Research)
— id: 109237, year: 2002, vol: 43, page: 480, stat: Journal Article,

Does menopausal hormone replacement therapy interact with known factors to increase risk of breast cancer?
Ursin, Giske; Tseng, Chiu-Chen; Paganini-Hill, Annlia; Enger, Shelley; Wan, Peggy C; Formenti, Silvia; Pike, Malcolm C; Ross, Ronald K
2002 Feb 1;20(3):699-706, Journal of clinical oncology
PURPOSE: We and other investigators have previously shown that postmenopausal combined estrogen and progestin replacement therapy (EPRT) increases the risk of breast cancer and that the risk associated with EPRT is substantially higher than for estrogen replacement therapy (ERT) alone. The present study was conducted to determine whether any particular subgroup of women are at particularly high risk of breast cancer if they use EPRT and whether tumor characteristics in women who develop cancer while on ERT or EPRT are different from those in women not using ERT or EPRT. PATIENTS AND METHODS: We conducted a population-based case-control study in Los Angeles, CA, with patients diagnosed with breast cancer in the late 1980s and early 1990s. Control subjects were matched to patients on age, ethnicity, and neighborhood of residence. We present data on 1,897 postmenopausal patients and 1,637 controls aged 55 to 72 years who had not undergone a simple hysterectomy. RESULTS: Relative risk of breast cancer associated with EPRT use did not vary with body mass index (body mass index at or below v above median [24.6 kg/m(2)]; P =.98), alcohol intake (> or + one v < one drink per week; P =.16), parity (nulliparous v parous; P =.45), history of benign breast disease (yes v no; P =.99), or family history of breast cancer (first degree v none; P =.57). All of these results were compatible with our previously reported estimate of an increased risk of breast cancer of 5% per year of use of EPRT. Hormone users, principally EPRT users, were more likely to have hormone receptor--positive, especially progesterone-positive, tumors. CONCLUSION: We found no evidence that the risk of breast cancer associated with EPRT is limited to subgroups of women with specific cofactors. Tumors in EPRT users are more often hormone receptor--positive, indicating that they may have a better prognosis than breast cancer overall
— id: 93558, year: 2002, vol: 20, page: 699, stat: Journal Article,

Development of tumor-infiltrating lymphocytes in breast cancer after neoadjuvant paclitaxel chemotherapy
Demaria S; Volm MD; Shapiro RL; Yee HT; Oratz R; Formenti SC; Muggia F; Symmans WF
2001 Oct;7(10):3025-3030, Clinical cancer research
PURPOSE: Neoadjuvant chemotherapy for breast cancer creates new possibilities for the analysis of biological factors in the tumor and/or host, which may play a role in the response to treatment. In this study we analyzed whether changes in local antitumor immunity take place after neoadjuvant paclitaxel therapy and if they correlate with response to treatment. Experimental Design: Neoadjuvant chemotherapy (paclitaxel, 200 mg/m2 q2w, 4 treatments) was followed by definitive surgical management. Histological sections from the pre- and post-treatment surgical specimens of 25 patients were analyzed for the extent of lymphocytic infiltration and presence of tumor infiltrating lymphocytes (TILs). The cumulative apoptotic response in the tumor after the first dose of paclitaxel was also studied in 10 of 25 patients. RESULTS: Pretreatment lymphocytic infiltrate in the tumor was minimal in the majority of patients and showed no relationship with clinical response. In the patients without TILs before treatment, development of TILs after treatment was noted in 0/3 (0%) patients with stable disease, 3/12 (25%) patients with clinical partial response, and 4/6 (67%) patients with clinical complete response and pathological residual disease. These correlated with the tumor cell apoptotic response to the first dose of paclitaxel. CONCLUSIONS: These results suggest that development of TILs after treatment correlates with clinical response to neoadjuvant paclitaxel therapy. The possible mechanism(s) whereby neoadjuvant chemotherapy may lead to induction of antitumor T cells is discussed. Immunological processes may influence the response of breast cancer patients to neoadjuvant treatment
— id: 24141, year: 2001, vol: 7, page: 3025, stat: Journal Article,

Toxicity of therapy and quality of life of patients treated for CNS tumors
Formenti SC; Bettini A
Combined modality therapy of central nervous system tumors New York : Springer, 2001,
— id: 5317, year: 2001, vol: , page: 595, stat: Chapter,

Treatment of CNS lymphomas
Formenti SC; Bettini A
Combined modality therapy of central nervous system tumors New York : Springer, 2001,
— id: 5318, year: 2001, vol: , page: 429, stat: Chapter,

Clinical course of locally advanced breast cancer (LABC) patients with pathological response to primary concurrent 5-fluorouracil and radiation (FU/RT)
Formenti, S. C.; Cohen, D.; Tsao-Wei, D. D.; Muggia, F. M.
2001 ;51(3 Supplement 1):195-196, International journal of radiation oncology biology physics
— id: 109249, year: 2001, vol: 51, page: 195, stat: Journal Article,

Adjuvant hypofractionated conformal radiation to the tumor bed in selected post-menopausal women with T1 breast cancers: A pilot-feasibility study
Formenti, SC; Rosenstein, BS; Jozsef, G
2001 ;7(6):548-548 #P34, Cancer journal
— id: 109273, year: 2001, vol: 7, page: 548, stat: Journal Article,

Chemoradiation for patients with cervical cancer
Muggia F; Formenti SC; Curtin J
Progress in oncology 2001 Boston MA : Jones & Bartlett, 2001,
— id: 5316, year: 2001, vol: , page: 168, stat: Chapter,

Increased breast cancer tumor localization and enhanced cytotoxicity of radioimmunotherapy and chemotherapy combinations
Ng, B; Kramer, E; Ceriani, R; Volm, M; Hamilton, A; Muggia, F; Formenti, S; Furmanski, P; Liebes, L
2001 ;69(3):303-303 #527, Breast cancer research & treatment
— id: 109250, year: 2001, vol: 69, page: 303, stat: Journal Article,

Postmastectomy radiotherapy: Clinical practice guidelines of the American Society of Clinical Oncology
Recht, A; Edge, SB; Solin, LJ; Robinson, DS; Estabrook, A; Fine, RE; Fleming, GF; Formenti, S; Hudis, C; Kirshner, JJ; Krause, DA; Kuske, RR; Langer, AS; Sledge, GW; Whelan, TJ; Pfister, DG
2001 Mar 1;19(5):1539-1569, Journal of clinical oncology
Objective: To determine indications for the use of postmastectomy radiotherapy (PMRT) for patients with invasive breast cancer with involved axillary lymph nodes or locally advanced disease who receive systemic therapy. These guidelines are Intended for use in the care of patients outside of clinical trials. Potential Intervention: The benefits and risks of PMRT in such patients, as well as subgroups of these patients, were considered. The details of the PMRT technique were also evaluated. Outcomes: The outcomes considered included freedom from local-regional recurrence, survival (disease-free and overall), and long-term toxicity. Evidence: An expert multidisciplinary panel reviewed pertinent information from the published literature through July 2000; certain investigators were contacted for more recent and, in some cases, unpublished information. A computerized search was performed of MEDLINE data; directed searches based on the bibliographies of primary articles were also performed. Values: Levels of evidence and guideline grades were assigned by the Panel using standard criteria. A 'recommendation' was made when level I or II evidence was available and there was consensus as to its meaning. A 'suggestion' was made based on level III, IV, or V evidence and there was consensus as to its meaning. Areas of clinical importance were pointed out where guidelines could not be formulated due to insufficient evidence or lack of consensus. Recommendations: The recommendations, suggestions, and expert opinions of the Panel are described in this article. Validation: Seven outside reviewers, the American Society of Clinical Oncology (ASCO) Health Services Research Committee members, and the ASCO Board of Directors reviewed this document. J Clin Oncol 19:1539-1569. (C) 2001 by American Society of Clinical Oncology
— id: 27489, year: 2001, vol: 19, page: 1539, stat: Journal Article,

Serial fine needle aspirations during neoadjuvant chemotherapy: Assessment of apoptotic responses in breast cancer
Symmans, W. F.; Volm, M.; Shapiro, R. L.; Demaria, S.; Yee, H.; Formenti, S. C.; Muggia, F.
2001 ;8(Supplement 1):S46-S46, International journal of molecular medicine
— id: 109251, year: 2001, vol: 8, page: S46, stat: Journal Article,

Unresectable primary and recurrent head and neck tumors: effect of hyperthermia and carboplatin--preliminary experience
Chang P; Sapozink MD; Grunberg SM; Jozsef G; Rice DM; Formenti SC; Streeter OE Jr
2000 Mar;214(3):688-692, Radiology
PURPOSE: To perform a single-arm study to determine the effectiveness of and potential toxic reactions to local hyperthermia and systemic carboplatin (cis-diammine-1,1-cyclobutane dicarboxylate platinum II) for the treatment of advanced or recurrent squamous cell carcinomas of the head and neck. MATERIALS AND METHODS: Eight patients with squamous cell carcinoma of the head and neck and stage IV disease (N2 or N3 neck adenopathy) or recurrent local-regional disease and who were previously and definitively treated were included in the study. Thermochemotherapy was administered every 4 weeks. Recorded end points were tumor response, duration of response, incidence of distant metastases, survival, cause of death, and toxic reactions. RESULTS: One patient had a complete response to therapy, and two had a partial response. Five patients had no response or developed progressive disease during therapy. Six patients died after 4-13 months of progressive disease. Two long-term survivors received radiation therapy; one also underwent surgical resection for residual neck disease. Each thermochemotherapeutic session was well tolerated, with minimal discomfort. Toxic reactions included hypotension, vomiting, hyponatremia, anemia, thrombocytopenia, and infection at the site of administration. There were no life-threatening toxic reactions. CONCLUSION: The combined use of hyperthermia and carboplatin shows potential in the management of unresectable head and neck tumors and is safe and well tolerated. Further studies on thermochemotherapy are warranted to assess its potential
— id: 34950, year: 2000, vol: 214, page: 688, stat: Journal Article,

Increase in the lymphocytic infiltrate in breast cancer after neoadjuvant paclitaxel chemotherapy
Demaria, Sandra; Volm, M. D.; Shapiro, R. L.; Yee, H. T.; Oratz, R.; Formenti, S.; Muggia, F.; Symmans, W. F.
2000 ;43(41):334-334, Proceedings (American Association for Cancer Research)
— id: 109238, year: 2000, vol: 43, page: 334, stat: Journal Article,

Update on impact of moderate dose of adjuvant radiation on urinary continence and sexual potency in prostate cancer patients treated with nerve-sparing prostatectomy
Formenti SC; Lieskovsky G; Skinner D; Tsao-Wei DD; Groshen S; Petrovich Z
2000 Sep 1;56(3):453-458, Urology
OBJECTIVES: Adjuvant radiotherapy to the prostatic bed at moderate doses of 45 to 54 Gy achieves results comparable to higher doses. We studied the effect of moderate doses of postoperative radiation therapy on urinary continence and sexual potency in prostate cancer patients who had undergone nerve-sparing prostatectomy. METHODS: Between November 1983 and December 1992, 255 prostate cancer patients were selected to undergo nerve-sparing prostatectomy. A total of 94 (37%) patients had received adjuvant postoperative radiotherapy, 45 to 54 Gy to the prostatic bed, based on microscopic positive margins, seminal vesicle involvement, and/or Gleason score. Subjective patient reports regarding the potency and urinary continence status were recorded during a semistructured telephone interview at 3 or more years after treatment. The findings in irradiated and nonirradiated patients were compared and correlated to those obtained from the same patients preoperatively and 1 year postoperatively. RESULTS: At 3 or more years of follow-up no significant difference among irradiated and nonirradiated patients was detected. Most patients described optimal urinary continence and approximately one third had maintained potency after bilateral nerve-sparing prostatectomy. None of the patients who had undergone unilateral nerve-sparing surgery remained potent. Using a multivariable analysis, the significant predictors for maintaining potency were the status at 1 year postoperatively and bilateral versus unilateral nerve-sparing procedure. CONCLUSIONS: Doses of adjuvant radiation therapy in the range used (45 to 54 Gy) did not affect the long-term pattern of maintenance of either function
— id: 34947, year: 2000, vol: 56, page: 453, stat: Journal Article,

BRCA1/2 germline mutations: a marker for radioresistance or radiosensitivity?
Formenti SC; Preston-Martin S; Haffty BG
2000 Mar;18(5):1159-1160, Journal of clinical oncology
— id: 34951, year: 2000, vol: 18, page: 1159, stat: Journal Article,

Low HER 2/NEU gene expression is associated with pathological response to primary paclitaxel and radiation in locally advanced breast cancer (LABC)
Formenti, S. C.; Groshen, S.; Florentine, B.; Park, M. J.; Danenberg, P. V.
2000 ;48(3 Supplement):143-143, International journal of radiation oncology biology physics
— id: 109254, year: 2000, vol: 48, page: 143, stat: Journal Article,

Adjuvant hypofractionated partial breast 3D radiation in selected post-menopausal women with T1 cancers: A pilot-feasibility study
Formenti, SC; Jozsef, G
2000 ;217(3):441-442 #987, Radiology
— id: 109274, year: 2000, vol: 217, page: 441, stat: Journal Article,

Long-term effects on urinary continence and sexual potency of post-operative radiation (4555 Gy) after nerve-sparing prostatectomy
Formenti, Silvia C.; Lieskovsky, Gary; Skinner, Donald; Groshen, Susan; Petrovich, Zbigniew
2000 ;6(2):115-115, Cancer journal
— id: 109253, year: 2000, vol: 6, page: 115, stat: Journal Article,

Pilot study of concurrent paclitaxel and radiation as preoperative treatment of locally advanced breast cancer (LABC): Clinical and pathological response
Formenti, Silvia C.; Spicer, Darcy; Skinner, Kristen A.; Cohen, Deirdre; Groshen, Susan; Florentine, Barbara
2000 ;6(2):111-111, Cancer journal
— id: 109252, year: 2000, vol: 6, page: 111, stat: Journal Article,

Gene expression profiling of paclitaxel-responsive and non-responsive locally advanced breast cancers
Formenti, Silvia; Danenberg, K.; Park, M.; Tsao-Wei, D.; Danenberg, P. V.
2000 ;43(41):335-335, Proceedings (American Association for Cancer Research)
— id: 109239, year: 2000, vol: 43, page: 335, stat: Journal Article,

In vitro hyperfractionated radiation (RT) and paclitaxel in wild and mutant p53 breast cancer cell lines
Hill, Colin K.; Williams-Hill, D. M.; Giaconi, J.; Danenberg, K.; Danenberg, P.; Formenti, S. C.
2000 ;43(41):245-245, Proceedings (American Association for Cancer Research)
— id: 109240, year: 2000, vol: 43, page: 245, stat: Journal Article,

Application of radiosurgery principles to a target in the breast: a dosimetric study
Jozsef G; Luxton G; Formenti SC
2000 May;27(5):1005-1010, Medical physics
PURPOSE: To investigate the technical and physical feasibility of using a radiosurgery-like technique to irradiate a small target within the breast with a single fraction. MATERIAL AND METHODS: During diagnostic biopsy, a tantalum surgical clip is placed in the lesion identified at mammography. Transverse CT scans over the entire breast are obtained, as the patient lies prone on a special table that allows the breast to hang down. The clip is used as a reference point to define the isocenter of the radiation treatment. RESULTS: The clip is visible on port films taken with a 4 MV beam, allowing the isocenter to be set to its planned location. No movement of the hanging breast is visually detected. The possible beam directions are enclosed by a 220 degrees horizontal x 180 degrees vertical angular interval. Dosimetry of two 'radiosurgical' examples, (A) seven fixed horizontal beams and (B) six 45 degrees arcs and a 90 degrees sagittal arc using a 4 MV x-ray beam with a 32 mm diameter collimator, are discussed. Both field arrangements produce adequate tumor coverage: the minimum target dose is 83% of the dose maximum in the fixed beam arrangement and 86% in the multiarc setup. In arrangement A the lung and other tissues external to the breast receive dose only from scattered radiation. In arrangement B the maximum lung dose is less than 5% of the dose to isocenter. CONCLUSION: From a dosimetric point of view both described techniques are feasible, and the radiosurgery-like treatment is executable
— id: 34948, year: 2000, vol: 27, page: 1005, stat: Journal Article,

Depression among Latina cervical cancer patients
Meyerowitz, Beth E; Formenti, Silvia C; Ell, Kathleen O; Leedham, Beth
2000 ;19(3):352-371, Journal of social & clinical psychology
This study was designed to begin to address gaps in the literature on psychological adjustment in minority cancer patients. The authors interviewed 50 indigent, Latina cervical cancer patients (aged 25-80 yrs) who were being treated in a large, urban, county hospital. The goals of the study were to describe patients' cancer-related and contextual experiences and to determine whether aspects of patients' experiences could predict depression. Patients reported high levels of depression and of stress related to socioeconomic and immigration status. Although patients appeared to have good social support overall, most wanted additional access to cancer-related support. As hypothesized, contextual variables, general social support and stress, were significant predictors of depression. Additionally, some cancer-related variables, specifically physical symptoms associated with radiation and practical barriers to receiving treatment, added significantly to the prediction of depression.
— id: 109222, year: 2000, vol: 19, page: 352, stat: Journal Article,

Preoperative paclitaxel and radiotherapy for locally advanced breast cancer: surgical aspects
Skinner KA; Silberman H; Florentine B; Lomis TJ; Corso F; Spicer D; Formenti SC
2000 Mar;7(2):145-149, Annals of surgical oncology
INTRODUCTION: Approximately 15% of breast cancer patients present with large tumors that involve the skin, the chest wall, or the regional lymph nodes. Multimodality therapy is required, to provide the best chance for long-term survival. We have developed a regimen of paclitaxel, with concomitant radiation, as a primary therapy in patients with locally advanced breast cancer. METHODS: Eligible patients had locally advanced breast cancer (stage IIB or III). After obtaining informed consent, patients received paclitaxel (30 mg/m2 during 1 hour) twice per week for 8 weeks and radiotherapy to 45 Gy (25 fractions, at 180 cGy/fraction, to the breast and regional nodes). Patients then underwent modified radical mastectomy followed by postoperative polychemotherapy. RESULTS: Twenty-nine patients were enrolled. Of these, 28 were assessable for clinical response and toxicity, and 27 were assessable for pathological response. Objective clinical response was achieved in 89%. At the time of surgery, 33% had no or minimal microscopic residual disease. Chemoradiation-related acute toxicity was limited; however, surgical complications occurred in 41% of patients. CONCLUSIONS: Preoperative paclitaxel with radiotherapy is well tolerated and provides significant pathological response, in up to 33% of patients with locally advanced breast cancer, but with a significant postoperative morbidity rate
— id: 34949, year: 2000, vol: 7, page: 145, stat: Journal Article,

Paclitaxel-induced apoptosis and mitotic arrest assessed by serial fine-needle aspiration: implications for early prediction of breast cancer response to neoadjuvant treatment
Symmans WF; Volm MD; Shapiro RL; Perkins AB; Kim AY; Demaria S; Yee HT; McMullen H; Oratz R; Klein P; Formenti SC; Muggia F
2000 Dec;6(12):4610-4617, Clinical cancer research
The extent of tumor reduction from neoadjuvant chemotherapy for breast cancer correlates with outcome. We investigated whether the initial cellular responses to paclitaxel are related to the extent of tumor reduction. Eleven women with breast cancer received paclitaxel (every 2 weeks for 4 cycles) as neoadjuvant treatment. Serial fine-needle aspirations (FNA; 25-gauge, 1 pass) were obtained before treatment and at 24, 48, 72, and 96 h after the first paclitaxel dose. Microscopic counts of apoptotic and mitotic indices were performed. The change in cancer volume from treatment was determined using radiological measurements with allowance for change in the histopathological amount of cancer. Apoptotic and mitotic responses usually subsided within 4 days. The duration of the initial apoptotic response was different for women with different treatment results. Cumulative apoptotic response for the first 4 days inversely correlated with the proportion of residual cancer after neoadjuvant treatment. FNA is a versatile clinical method to obtain breast cancer cells for therapy response studies. Apoptotic response to the first dose of paclitaxel is almost complete within 4 days, implying that more frequent (weekly) paclitaxel dosing might be beneficial. The apoptotic response to the first dose of paclitaxel appeared to predict the amount of cancer reduction from this treatment. This is a promising start toward the development of an early chemopredictive assay for paclitaxel treatment of breast cancer
— id: 22642, year: 2000, vol: 6, page: 4610, stat: Journal Article,

Breast radiation therapy
Formenti SC
Breast care : a clinical handbook for women's primary health care providers New York : Springer, 1999,
— id: 5322, year: 1999, vol: , page: 242, stat: Chapter,

Measures to optimize quality of life in patients treated for geniturinary tumors
Formenti SC
Carcinoma of the kidney and testis, and rare urologic malignancies : innovations in management New York : Springer, 1999,
— id: 5319, year: 1999, vol: , page: 421, stat: Chapter,

Radiation therapy for breast conservation
Formenti SC
Breast care : a clinical handbook for women's primary health care providers New York : Springer, 1999,
— id: 5321, year: 1999, vol: , page: ?, stat: Chapter,

Second malignancies in genitourinary cancers
Formenti SC; Corso F
Carcinoma of the kidney and testis, and rare urologic malignancies : innovations in management New York : Springer, 1999,
— id: 5320, year: 1999, vol: , page: ?, stat: Chapter,

Concurrent paclitaxel and radiation therapy for breast cancer
Formenti SC; Symmans WF; Volm M; Skinner K; Cohen D; Spicer D; Danenberg PV
1999 Apr;9(2 Suppl 1):34-42, Seminars in radiation oncology
Few studies have evaluated the role of concurrent chemoradiation therapy in the management of locally advanced breast cancer. The availability of radiosensitizing chemotherapeutic agents that are effective in breast cancer and the encouraging results achieved by concurrent chemoradiation in other malignancies have prompted us to investigate this approach. Paclitaxel is a promising agent for use with concurrent radiotherapy because of its single-agent efficacy profile and its radiosensitizing effects. A clinical protocol of preoperative paclitaxel and radiation in locally advanced breast cancer is ongoing at our institution to test feasibility, measure pathologic response at mastectomy, and explore association of pathologic response with molecular tumor markers. Initially, the study was designed to test weekly paclitaxel at a dose of 60 mg/m2 during radiation therapy, delivered 5 days a week at 200 cGy fractions to a total dose of 50 Gy over 5 weeks. Due to severe skin toxicity in the first two patients, the protocol was amended to change the scheduling of paclitaxel to 30 mg/m2 twice weekly and to reduce the radiation to 180 cGy fractions to a total dose of 45 Gy, delivered 5 days a week over 5 weeks. Presently, 13 patients have been accrued; preliminary data indicate good tolerance to twice-weekly paclitaxel, and four of eight evaluable patients have achieved pathologic response (one patient who received the weekly regimen and three who received the twice-weekly regimen). In addition, sequential fine-needle aspirations of palpable breast cancers were obtained in patients enrolled in a parallel study of preoperative single-agent paclitaxel (200 mg/m2 every 2 weeks, for a total of four cycles before breast surgery). Preliminary results suggest that a steep increase in the mitotic index occurs during the first day after paclitaxel administration and plateaus between the second and the third day, then decreases to pretreatment values. The peak apoptotic index occurs at approximately 72 hours after paclitaxel administration and decreases at approximately 98 hours. These initial findings suggest that twice-weekly dosing of paclitaxel may optimize recruitment of cells into the G2/M phase of the cell cycle, the most radiosensitive phase
— id: 34952, year: 1999, vol: 9, page: 34, stat: Journal Article,

Molecular predictors of response to paclitaxel in breast cancer
Formenti, S. C.; Salonga, D.; Park, J.-M.; Skinner, K.; Corso, F.; Horwitz, S. B.; Kavallaris, M.; Symmans, W. F.; Volm, M.; Danenberg, K.; Danenberg, P. V.
1999 ;40(41):495-495, Proceedings (American Association for Cancer Research)
— id: 109241, year: 1999, vol: 40, page: 495, stat: Journal Article,

An update on radiation therapy in breast cancer
Formenti, S; Green, G
1999 Apr;13(2):373-89, vi, Hematology-oncology clinics of North America
Radiation therapy plays an important role in the management of both invasive and noninvasive breast cancer. During the last 20 years, the availability of radiation therapy has made it possible to test the feasibility and safety of breast preservation after the diagnosis of early-stage breast cancer. This article summarizes some of the ongoing controversies concerning the use of radiation therapy in the multidisciplinary management of breast cancer
— id: 109140, year: 1999, vol: 13, page: 373, stat: Journal Article,

Primary paclitaxel in breast cancer: Does beta-tubulin predict pathologic response?
Formenti, SC; Muggia, FM; Volm, M; Danenberg, K; Danenberg, PV
1999 FEB ;26(1):35-35, Seminars in oncology
— id: 98325, year: 1999, vol: 26, page: 35, stat: Journal Article,

Twice-weekly paclitaxel and radiation therapy in locally advanced breast cancer: Clinical and pathological response
Formenti, SC; Skinner, K; Spicer, D; Muggia, F; Danenberg, K; Danenberg, P
1999 ;26(6):6-6, Seminars in oncology
— id: 109224, year: 1999, vol: 26, page: 6, stat: Journal Article,

Paclitaxel and radiation therapy in locally advanced breast cancer: Preliminary clinical results
Formenti, SC; Symmans, F; Volm, M; Skinner, K; Perez, E; Muggia, F
1999 FEB ;26(1):29-29, Seminars in oncology
— id: 98324, year: 1999, vol: 26, page: 29, stat: Journal Article,

Prolonged combination chemo-/radio-therapy with paclitaxel or 5-FU may after expression of cell cycle regulation and or tumor suppressor genes that determine the cytotoxic effectiveness in human tumor cell lines
Hill, C. K.; Williams-Hill, D. M.; Giaconi, J.; Savilia, N.; Danenberg, K.; Danenberg, P.; Formenti, S. C.
1999 ;40(41):642-642, Proceedings (American Association for Cancer Research)
— id: 109242, year: 1999, vol: 40, page: 642, stat: Journal Article,

Adjuvant radiotherapy in patients with pathologic Stage C (pT3N0) adenocarcinoma of the prostate
Petrovich, Z; Lieskovsky, G; Langholz, B; Bochner, B; Formenti, S; Streeter, O; Skinner, D G
1999 Jun;53(6):1184-1193, Urology
OBJECTIVES: This report is an update on the outcomes in the management of pathologic Stage C (T3N0) prostate cancer (CaP) with postoperative irradiation. METHODS: Between 1976 and 1994, 311 patients with pathologic Stage C CaP were treated with radical prostatectomy. Pathologic stage was as follows: C1, 60 patients (19%), C2, 146 patients (47%), and C3, 105 patients (34%). Gleason score was 2 to 4 in 10 patients (3.2%), 5 to 6 in 121 (39%), 7 in 101 (32%), and 8 to 10 in 76 (24%); median prostate-specific antigen (PSA) level was 11.9 ng/mL. Postoperative irradiation consisted of a median dose of 48 Gy. Follow-up was up to 18 years (median 5). RESULTS: The 10-year actuarial survival was 81% and 10-year disease-free survival was 51%. Pathologic stage and Gleason score were independently predictive of recurrence, each with P >0.001 after controlling for the other. Patients with pathologic Stage C3 and Gleason score 7 to 10 were in the worst prognostic category and had 5.4 times the risk of recurrence compared with patients with pathologic Stage C1-C2, Gleason score 2 to 6. Preoperative PSA was a good (P = 0.02) predictor of disease-free survival. Clinical recurrence was seen in 28 patients (9%), including 10 (3.2%) with local recurrence. PSA recurrence (PSA greater than 0.05 ng/mL) developed in 68 patients (22%). CONCLUSIONS: With the known limitations of a nonrandomized clinical trial, on the basis of the experience of this study we recommend the use of moderate dose, limited-field postoperative radiotherapy in patients with pathologic Stage C disease with Gleason score greater than 4
— id: 109141, year: 1999, vol: 53, page: 1184, stat: Journal Article,

Comparison of outcomes of radical prostatectomy with and without adjuvant pelvic irradiation in patients with pathologic stage C (T3N0) adenocarcinoma of the prostate
Petrovich, Z; Lieskovsky, G; Langholz, B; Bochner, B; Formenti, S; Streeter, O; Skinner, D G
1999 Aug;22(4):323-331, American journal of clinical oncology
Patients with localized adenocarcinoma of the prostate gland (CaP) are frequently (approximately 50%) found at radical prostatectomy to have extracapsular disease or positive surgical margins. The management of these patients is a subject of controversy because some question the impact of this manifestation of CaP on patient survival or disease-free survival. Between 1976 and 1991, 241 patients with pathologic stage C (T3N0) were treated in this medical center. Of these 241 patients, 201 (83%) received a planned postoperative pelvic irradiation consisting of 48 Gy given to the prostatic fossa, whereas 40 (17%) patients were treated with radical prostatectomy alone. The two study urologists selected these patients not to receive postoperative irradiation based on intraoperative findings and important prognostic factors. Comparison of treatment outcomes in these two treatment groups is a subject of this report. The 201 patients treated with surgery-radiotherapy (S+RT) combination had a higher pathologic stage, greater incidence of seminal vesicle involvement, p = 0.002, and higher mean and median preoperative prostate-specific antigen level, p < 0.0001, than the 40 surgery (S) alone patients. There was no significant difference in the incidence of higher Gleason's score by the treatment group, p = 0.14. In univariate analysis, there was no significant difference in survival, disease-free survival, and time to failure between the two treatment groups. In multivariate analysis after controlling for pathologic stage and Gleason's score, the 201 adjuvant radiotherapy patients were predicted to have recurrence at 68% (95% confidence interval 39%-118%) the rate of the 40 surgery-alone patients. Local recurrence with or without metastatic disease was found in 10% of surgery-alone patients as compared to 5% in those also receiving postoperative irradiation. Treatment tolerance was very good with minor radiotherapy complications only. There was no significant difference in the incidence of incontinence between the two treatment arms. In summary: (a) The use of moderate-dose postoperative radiotherapy was of low toxicity and it did not increase the incidence of incontinence. (b) Local recurrence was 5% in S+RT and 10% in S-alone patients. (c) In multivariate analysis, S+RT patients had 68% rate of recurrence of S-alone patients. (d) Adjuvant RT probably reduces the risk of recurrence in patients with poor prognostic factors. (e) These data need to be interpreted with caution because of the nonrandomized nature of the study
— id: 109142, year: 1999, vol: 22, page: 323, stat: Journal Article,

MDR1 gene expression in primary and advanced breast cancer
Yang, X; Uziely, B; Groshen, S; Lukas, J; Israel, V; Russell, C; Dunnington, G; Formenti, S; Muggia, F; Press, M F
1999 Mar;79(3):271-280, Laboratory investigation
P-glycoprotein (Pgp)-associated multidrug resistance (MDR) is related to intrinsic and acquired cross resistance to anthracyclines, vinca alkaloids, and other antineoplastic antibiotics. Expression of MDR1 is widely considered to play an important role in conferring resistance to adjuvant chemotherapy in women with breast tumor cells in women with disseminated disease, although data supporting this view is, at best, conflicting. The expression of MDR1 gene and its gene product, P-glycoprotein, was investigated in primary and advanced breast cancers (both previously untreated and previously treated on specific treatment protocols) to assess the role of P-glycoprotein in determining responsiveness to adjuvant chemotherapy. Expression was assessed by immunohistochemistry, reverse transcription-PCR (RT-PCR), Northern Blot and Western Blot. MDR1 mRNA was detected in 40% of the breast cancers tested by RT-PCR with 40 cycles of PCR amplification. When reducing the PCR amplification cycles to 28, the MDR1 gene expression signal disappeared from breast cancers of the highest expressers; however, known MDR1 positive control normal tissues, such as adrenal, kidney, and liver continued to show an expression product. Western and Northern blots failed to demonstrate the MDR1 gene product, P-glycoprotein, in these breast cancers. In contrast, physiologic levels of P-glycoprotein was clearly detected in normal adrenal, kidney, and liver by these techniques. Immunohistochemistry confirmed that breast carcinoma cells lacked P-glycoprotein expression; however, interstitial mononuclear cells, morphologically consistent with lymphocytes or macrophages did show immunostaining in some of these breast tumors. MDR1 gene expression identified by RT-PCR was not correlated either with response to paclitaxel therapy (29 patients able to be evaluated, p = 0.34, Fisher Exact Test) or overall survival (32 breast cancer patients with clinical follow-up information, p = 0.336, log rank). In conclusion, P-glycoprotein was not expressed in breast carcinoma cells at significant levels, although it was expressed in stomal lymphocytes or macrophages. These results suggest that P-glycoprotein does not play a significant role in multidrug resistance of breast cancer
— id: 109139, year: 1999, vol: 79, page: 271, stat: Journal Article,

Comprehensive needs assessment of clinical breast evaluation skills of primary care residents
Chalabian, J; Formenti, S; Russell, C; Pearce, J; Dunnington, G
1998 Mar;5(2):166-172, Annals of surgical oncology
BACKGROUND: Health care reform places primary care (PC) physicians in an increasingly significant role for breast cancer screening and diagnosis. This study assessed the adequacy of traditional PC resident training to prepare physicians for this front-line role. METHODS: Sixty-eight primary care residents, representing seven training programs, participated in a multidimensional needs assessment study of clinical breast evaluation skills. RESULTS: Performance deficiencies noted in each component were most significant in (1) common breast problem management (problem-solving mean 44.51 +/- 11.01); (2) breast examination skills (mean 49.65 +/- 14.48%); and (3) lump detection sensitivity (mean 40.20 +/- 17.10%). Overall examination reliability was good (alpha = .82). Factorial ANOVA revealed significant performance differences among training programs. Residency programs with higher performance levels reported dedicated breast curricula, and residents rated these programs as providing more adequate training. Programs with poorer performance in breast examination lacked curriculum emphasis, with residents describing training received as poor to fair. CONCLUSION: This study demonstrated performance deficits in the clinical breast evaluation skills of graduating PC residents that have not been captured by traditional evaluation methodologies. This may represent a limitation in the ability of many PC physicians to effectively screen and diagnose patients with breast cancer
— id: 109149, year: 1998, vol: 5, page: 166, stat: Journal Article,

Locally advanced breast cancer : a model for translational research
Formenti SC
1998 ;25(5 Suppl):14-24, Seminars in oncology
— id: 109305, year: 1998, vol: 25, page: 14, stat: Journal Article,

Management of patients with pelvic recurrence following radical cysectomy
Formenti SC; Simoneau A
Carcinoma of the bladder : innovations in management New York : Springer, 1998,
— id: 5312, year: 1998, vol: , page: 251, stat: Chapter,

Concurrent paclitaxel and radiation therapy in locally advanced breast cancer
Formenti, SC; Skinner, KA; Spicer, D; Russell, C; Cohen, D; Kutsch, K
1998 ;209P(1):248-248 #462, Radiology
— id: 109275, year: 1998, vol: 209P, page: 248, stat: Journal Article,

Molecular determinants of response of locally advanced breast cancer to 5-FU and radiation
Formenti, Silvia; Park, Ji Min; Salonga, Dennis; Williams-Hill, Donna; Danenberg, Kathleen; Muggia, Franco; Danenberg, Peter V.
1998 ;39(41):187-187, Proceedings (American Association for Cancer Research)
— id: 109243, year: 1998, vol: 39, page: 187, stat: Journal Article,

Radiosurgery of early breast cancer: A dosimetric study
Jozsef, G; Parisky, YR; Luxton, G; Formenti, SC
1998 ;209P(5):248-248 #461, Radiology
— id: 109256, year: 1998, vol: 209P, page: 248, stat: Journal Article,

Radical prostatectomy and postoperative irradiation in patients with pathological stage C (T3) carcinoma of the prostate
Petrovich, Z; Lieskovsky, G; Langholz, B; Formenti, S; Baert, L; Streeter, O; Skinner, D G
1998 Jan 1;40(1):139-147, International journal of radiation oncology biology physics
PURPOSE: Adenocarcinoma of the prostate is the most common human cancer of internal organs. Radical surgery is regarded by many to be the treatment of choice for capsule confined disease. Since accurate preoperative assessment of tumor stage is difficult to define, many patients are subsequently found to have pathological stage C (T3) disease. These patients should be considered for adjuvant radiotherapy. METHODS AND MATERIALS: A group of 201 PS C (T3) unselected patients, treated with radical prostatectomy and limited pelvic lymphadenectomy, received postoperative irradiation to the prostate bed. This radiotherapy was given between 42-90 days after surgery and consisted of a median dose of 48 Gy. Patient survival, disease free survival, time to clinical and chemical relapse and the incidence of local and systemic relapse were analyzed. The influence of multiple parameters on the treatment outcome including patient age, treatment period, clinical stage, pathological stage, Gleason's score, prostate specific antigen (PSA), radiotherapy techniques and radiation dose were examined using univariate and multivariate analysis. Follow-up ranged from 3 to 15 years, with a median of 5 years. RESULTS: The overall 5- and 10-year actuarial survival was 92% and 83% (median > 10 years), respectively and the 5- and 10-year disease-free survival (clinical and PSA) was 67% and 53% (median > 10 years), respectively. A total of 61 (30%) patients had a recurrence, including 23 (11%) patients who had clinical and 38 (19%) who had PSA recurrence. Of the 23 patients with clinical recurrence, 10 (5%) had local recurrence, including two patients who had local and systemic recurrence. Pathological stage and Gleason's score were independently predictive of recurrence (each with p < 0.001 after controlling for the other). Patients in the worst prognostic category with pathological stage C3 and Gleason's score 8-10 were predicted to be at 7.2 times the risk of recurrence, compared to stage C1 or C2 and Gleason's score 2-7 patients. Preoperative PSA level (> 25 ng/ml) was also an important independent factor predicting tumor recurrence, p = 0.05. All other investigated parameters were not significant in predicting tumor recurrence. This treatment program was very well tolerated by the study patients, with seven (3.5%) recorded with major and 18 (9%) with minor surgical complications, while 65% of patients had minor and clinically insignificant radiation complications. CONCLUSION: Surgery followed by moderate dose radiotherapy in patients with PS C (T3) prostatic carcinoma was well tolerated and resulted in excellent overall and disease free survival, with a low incidence of local recurrence. New treatment strategies need to be developed for patients with C3 tumors and those with high (8-10) Gleason's score and those with high (> 25 ng/ml) PSA level at diagnosis
— id: 109148, year: 1998, vol: 40, page: 139, stat: Journal Article,

Significance of the length of extended field radiotherapy in carcinoma of the cervix with periaortic metastases
Duong, PL; Morrow, PC; Formenti, SC; Langholz, B; Petrovich, Z; Klement, V
1997 ;205(1):1620-1620, Radiology
— id: 109276, year: 1997, vol: 205, page: 1620, stat: Journal Article,

Original p53 status predicts for pathological response in locally advanced breast cancer patients treated preoperatively with continuous infusion 5-fluorouracil and radiation therapy
Formenti SC; Dunnington G; Uzieli B; Lenz H; Keren-Rosenberg S; Silberman H; Spicer D; Denk M; Leichman G; Groshen S; Watkins K; Muggia F; Florentine B; Press M; Danenberg K; Danenberg P
1997 Dec 1;39(5):1059-1068, International journal of radiation oncology biology physics
PURPOSE/OBJECTIVE: 1) To test feasibility of preoperative continuous infusion (c.i.) 5-Fluorouracil (5-FU) and radiation (RT) in locally advanced breast cancer. 2) To study clinical and pathological response rates of 5-FU and radiation. 3) To attempt preliminary correlations between biological probes and pathological response. METHODS AND MATERIALS: Previously untreated, locally advanced breast cancer patients were eligible: only patients who presented with T3/T4 tumors that could not be resected with primary wound closure were eligible, while inflammatory breast cancer patients were excluded. The protocol consisted of preoperative c.i. infusion 5-FU, 200 mg/m2/day with radiotherapy, 50 Gy at 2 Gy fractions to the breast and regional nodes. At mastectomy, pathological findings were classified based on persistence of invasive cancer: pathological complete response (pCR) = no residual invasive cells in the breast and axillary contents; pathological partial response (pPR) = presence of microscopic foci of invasive cells in either the breast or nodal specimens; no pathological response (pNR) = pathological persistence of tumor. For each patient pretreatment breast cancer biopsies were analyzed by immunohistochemistry for nuclear grade, ER/PR hormonal receptors, her2/neu and p53 overexpression. RESULTS: Thirty-five women have completed the protocol and are available for analysis. 5-FU was interrupted during radiation in 10 of 35 patients because of oral mucositis in 8 patients, cellulitis in 1, and patient choice in another. Objective clinical response rate before mastectomy was 71% (25 of 35 patients): 4 CR, 21 PR. However, in all 35 patients tumor response was sufficient to make them resectable with primary wound closure. Accordingly, all patients underwent modified radical mastectomy: primary wound closure was achieved in all patients. At mastectomy there were 7 pCR (20%), 5 pPR (14%) and the remaining 23 patients (66%) had pathological persistence of cancer (pNR). Variables analyzed as potential predictors for pathological response (pPR and pCR) were: initial TNM clinical stage, clinical response, nuclear grade, hormonal receptor status, p53 overexpression, and Her2/neu overexpression in the pretreatment tumor biopsy. Only initial p53 status (lack of overexpression at immunohistochemistry) significantly correlated with achievement of a pathological response to this regimen (p = 0.010). CONCLUSION: The combination of c.i. 5-FU and radiation was well tolerated and generated objective clinical responses in 71% of the patients. With the limitation of the small sample size, the complete pathological response achieved (20%) compares favorably with that reported in other series of neoadjuvant therapy for similar stage breast cancer. These preliminary data suggest that initial p53 status predicts for pathological response (pPR and pCR) to the combination of c.i. 5-FU and radiotherapy in locally advanced breast cancer
— id: 34954, year: 1997, vol: 39, page: 1059, stat: Journal Article,

Radiosensitivity of Koch ileal reservoir
Formenti SC; Keren-Rosenberg S; Crocitto L; Skinner D; Petrovich Z
1997 Dec 1;39(5):1053-1057, International journal of radiation oncology biology physics
PURPOSE: To acquire preliminary information on the radiosensitivity of the Koch ileal reservoir by reviewing acute and late toxicity incurred by nine patients who received pelvic radiotherapy after cystoprostatectomy with lower urinary reconstruction utilizing a Koch ileal reservoir with bilateral uretero-ileal-urethrostomy. METHODS AND MATERIALS: All patients were irradiated because of synchronous locally advanced prostate cancer (pT3). A fourfield box technique at 100 cm source-axis-distance (SAD) with all fields treated every day at 1.8 Gy daily fractions, to a total dose of 45-50.40 Gy was used. The average AP portal dimension was 11 x 11 cm, and the average lateral was 7 x 8 cm. All portals were shaped using custom shields to optimize protection of normal tissues not suspected of tumor involvement (small bowel, posterior rectal wall). No attempt was made to shield the Koch ileal reservoir. For each patient, comparison of the treatment portals with the Kochgram radiography (gravity cystogram) confirmed the inclusion of the majority of the Koch ileal reservoir within the radiation fields. Acute and late morbidity was measured by RTOG toxicity criteria by retrospectively reviewing the patients' records. RESULTS: Only mild acute toxicity was reported by the patients: Six patients experienced grade 1 acute urinary toxicity and one suffered Grade 2 acute urinary toxicity. In four patients Grade 1 acute gastrointestinal toxicity occurred and in two patients Grade 2 toxicity occurred. With a median follow-up of 50 months late toxicity consisted mainly of microscopic hematuria in six patients and persistent frequency in two patients (with spontaneous improvement respectively at 4 and 6 months after radiation). No patients experienced acute or late Grade 3 or 4 genitourinary or gastrointestinal toxicity. CONCLUSION: The use of moderate doses of pelvic radiotherapy (45-50.40 Gy) at standard fractionation was well tolerated among nine patients who received pelvic radiation for invasive prostate cancer detected at the time of cystectomy and Koch ileal reservoir diversion. These preliminary data support the evidence that patients with a Koch ileal reservoir could safely undergo postoperative pelvic radiotherapy in these dose ranges and fractionation
— id: 34955, year: 1997, vol: 39, page: 1053, stat: Journal Article,

Radiosurgery of early breast cancer: A dosimetric study
Jozsef, G.; Luxton, G.; Petrovich, Z.; Formenti, S. C.
1997 ;46(1):37-37, Breast cancer research & treatment
— id: 109257, year: 1997, vol: 46, page: 37, stat: Journal Article,

Carboplatin as a radiation sensitizer in locally advanced cervical cancer: a pilot study
Muderspach LI; Curtin JP; Roman LD; Gebhardt JA; Klement V; Qian D; Morrow CP; Felix JC; Formenti SC; Muggia FM
1997 May;65(2):336-342, Gynecologic oncology
Radiation therapy is the mainstay in treatment of locally advanced cervical carcinoma. Several chemotherapeutic agents have been used as radiation sensitizers in the treatment of cervical cancer in an effort to improve local response and survival. A prospective study was designed to evaluate carboplatin as a radiosensitizer in advanced cervical cancer. Standard radiotherapy techniques were used to treat patients with Stage IIA-IIIB cervical cancer. Intravenous carboplatin was administered twice weekly concurrent with external beam radiation. Of 22 evaluable patients, there were 19 complete responders of whom 15 remain alive: 11 patients were alive and disease free at last visit for a median duration of 15 months follow-up (range, 4-43 months) and 4 patients remain alive with disease for a median duration of 17 months (range, 3-55 months). Seven have died, one of whom was without evidence of disease. There were no treatment-related deaths and no grade 4 toxicity. The most significant adverse effect was hematologic resulting in four patients with grade 3 neutropenia or anemia. There were no fistulae or late gastrointestinal or genitourinary complications. This pilot study suggests that carboplatin administered with standard radiation is safe, well-tolerated, and thus may be useful as a radiation sensitizer in the treatment of locally advanced cervical cancer
— id: 34956, year: 1997, vol: 65, page: 336, stat: Journal Article,

Preoperative 5-fluorouracil and radiation therapy for locally advanced breast cancer
Skinner KA; Dunnington G; Silberman H; Florentine B; Spicer D; Formenti SC
1997 Dec;174(6):705-707, American journal of surgery
BACKGROUND: Fifteen percent of breast cancer patients present with large tumors involving skin or chest wall. Often, surgery with primary wound closure is impossible. We used neoadjuvant chemoradiation in locally advanced breast cancer patients, in hopes of increasing resectability. METHODS: Eligible patients had locally advanced breast cancer deemed unresectable with primary wound closure. Patients received 8 weeks of infusional 5-fluorouracil (5-FU) 200 mg/m2 per day and radiation therapy to 50 Gy. Patients rendered resectable underwent modified radical mastectomy (MRM) followed up by chemotherapy. RESULTS: Of 30 evaluable patients, 73% had an objective clinical response. All were able to undergo MRM with primary wound closure; 63% had residual disease, 20% had minimal microscopic disease, and 17% had complete pathologic response. Treatment-related toxicity was minimal. Surgical morbidity was not increased. CONCLUSIONS: Infusional 5-FU with concomitant radiotherapy is well tolerated and effective at producing shrinkage in the majority of patients, converting inoperable breast cancer to easily resectable disease
— id: 34953, year: 1997, vol: 174, page: 705, stat: Journal Article,

MDR1 gene expression in primary and advanced breast cancer
Yang, X.; Uziely, B.; Groshen, S.; Lukas, J.; Israel, V.; Russell, C.; Dunnington, G.; Formenti, S.; Muggia, F.; Press, M. F.
1997 ;38(0):389-389, Proceedings (American Association for Cancer Research)
— id: 109244, year: 1997, vol: 38, page: 389, stat: Journal Article,

Impact of moderate dose of postoperative radiation on urinary continence and potency in patients with prostate cancer treated with nerve sparing prostatectomy
Formenti SC; Lieskovsky G; Simoneau AR; Skinner D; Groshen S; Chen SC; Petrovich Z
1996 Feb;155(2):616-619, Journal of urology
PURPOSE: We analyzed the impact on potency and urinary continence of moderate doses of radiation (45 to 54 Gy.) given postoperatively after nerve sparing prostatectomy. MATERIALS AND METHODS: Between 1983 and 1992, 294 of 762 prostate cancer patients were selected to undergo nerve sparing prostatectomy. Subjective patient reports regarding potency and urinary continence status were obtained preoperatively, 1 year postoperatively or 1 year after completion of radiation. RESULTS: Of the 294 patients 105 received postoperative radiotherapy (45 to 54 Gy.) to the prostatic bed. There were patients with more advanced stages of disease in the irradiated group, including 89% with stages C and D1 (pT3N0 and pT1 to 3, N1 to 3), compared to 14% with stages C and D1 (pT3N0 and pT1 to 3, N1 to 3) in the nonirradiated group (p < 0.001). No difference in urinary continence was noted in the irradiated (94%) compared to the nonirradiated group (92%, p = 0.64). Of the patients who underwent bilateral nerve sparing prostatectomy 44% who received and 48% who did not receive radiation had recovered potency at 1 year (p = 0.76). Of those who underwent unilateral nerve sparing prostatectomy 10% who received and 33% who did not receive radiation had recovered potency at 1 year (p = 0.14). Using multivariate analysis patient age younger than 63 years and bilateral versus unilateral nerve sparing procedures were significant predictors of potency. CONCLUSIONS: Our retrospective study suggests that at 1 year after treatment moderate doses of postoperative radiotherapy did not have a significant impact on the recovery of urinary continence and potency after nerve sparing prostatectomy. However, longer followup is required to determine the impact of this radiation protocol on long-term preservation of potency after nerve sparing prostatectomy
— id: 34958, year: 1996, vol: 155, page: 616, stat: Journal Article,

Abdomino-pelvic hyperthermia and intraperitoneal carboplatin in epithelial ovarian cancer: feasibility, tolerance and pharmacology
Formenti SC; Shrivastava PN; Sapozink M; Jozsef G; Chan KK; Jeffers S; Morrow PC; Muggia FM
1996 Jul 15;35(5):993-1001, International journal of radiation oncology biology physics
PURPOSE: To investigate the feasibility, toxicity, and pharmacokinetics of intraperitoneal (i.p.) carboplatin (CB) with concomitant abdomino-pelvic hyperthermia (HT) in advanced ovarian cancer patients. METHODS AND MATERIALS: Patients with residual disease mainly confined to the peritoneal cavity after platinum based chemotherapy received an initial course of i.p. CB for baseline pharmacokinetics followed by three cycles of i.p. CB with concomitant regional hyperthermia. The goal of HT was to achieve at least 45 min of intraperitoneal temperature > 42 degrees but < 50 degrees C while maintaining normal tissue temperatures < 43 degrees C and systemic body temperatures < 38 degrees C. No analgesic premedication was used. Thermometry was recorded by multisensor fiberoptic probes placed within the peritoneal cavity, bladder, vagina, and oral cavity. RESULTS: Thirteen patients received a total of 31 sessions. Our intraperitoneal temperature goal could not be achieved because of patient intolerance. At best, we could maintain intraperitoneal temperatures > 40 degrees C, for more than 40 min in 7 of 31 sessions. The average values of thermal variables were T90 = 40 degrees C, TAVE = 41 degrees C, TMIN = 38.2 degrees C, and TMAX = 42.9 degrees C. The mean maximum systemic temperature was 38 degrees C. Acute thermal toxicities requiring early interruption of hyperthermia were systemic temperature exceeding 38 degrees C (11 of 31), abdominal pain or generalized distress (20 of 31), and vomiting (2 of 31). Hematological toxicities were not increased by hyperthermia. Pharmacokinetics were consistent with enhanced clearance of CB by HT. Lower radio frequencies (< 75 MHz) achieved better heat deposition in the peritoneal cavity than higher frequencies (> 75 MHz). Two of the 13 patients (a Stage III and a Stage IV patient) are alive with no evidence of disease at 40 and 43 months from treatment. CONCLUSIONS: Intraperitoneal temperatures in the range of 40 degrees C maintained for approximately 40 min can be achieved within the described setting. The probability of successful induction of therapeutic intraperitoneal temperatures appears to be higher when frequencies below 75 MHz are used. Patients who are potentially platinum sensitive and have minimal residual disease could potentially benefit from the combined treatment under the conditions studied. However, this temperature-time range appears inadequate against platinum resistant disease, and/or bulky residual pelvic disease. Alternative approaches such as whole body hyperthermia and carboplatin are warranted to overcome some of the obstacles observed
— id: 34957, year: 1996, vol: 35, page: 993, stat: Journal Article,

Original p53 status predicts for pathological responses in locally advanced breast cancer treated pre-operatively with continuous infusion (c.i.) 5-fluorouracil (5FU) during radiotherapy
Formenti, S. C.; Dunnington, G.; Lenz, J.; Keren-Rosenberg, S.; Spicer, D.; Danenberg, K.; Danenberg, P.
1996 ;36(1 SUPPL.):179-179, International journal of radiation oncology biology physics
— id: 109255, year: 1996, vol: 36, page: 179, stat: Journal Article,

Stereotactic radiosurgery for primary and metastatic brain tumors
Petrovich, Z; Luxton, G; Formenti, S; Jozsef, G; Zee, C S; Apuzzo, M L
1996 ;14(5):445-454, Cancer investigation
— id: 76040, year: 1996, vol: 14, page: 445, stat: Journal Article,

Increased radiosensitivity of normal tissue fibroblasts in patients with acquired immunodeficiency syndrome (AIDS) and with Kaposi's sarcoma
Formenti SC; Chak L; Gill P; Buess EM; Hill CK
1995 Oct;68(4):411-412, International journal of radiation biology
Fibroblasts cultured from skin biopsies of patients with AIDS and Kaposi's sarcoma were found to be more radiosensitive than fibroblasts from non-HIV-infected-sources. This supports clinical observations of overt sensitivity to radiotherapy in some AIDS patients with Kaposi's sarcoma
— id: 34959, year: 1995, vol: 68, page: 411, stat: Journal Article,

Initial brachytherapy in the breast conservation approach to breast cancer
Formenti SC; Lucas G; Ibarra JA; Langholz B; Syed NM; Puthawala AA; Neblett D; Gowdy RA; Petrovich Z
1995 Aug;18(4):331-336, American journal of clinical oncology
The outcome of 100 consecutive newly diagnosed breast cancer patients treated between 1975 and 1985 within a protocol of planned segmental mastectomy and radiation therapy that included an initial brachytherapy boost is reported. Margins were not routinely inked in this study and the tumor bed was determined with the operating surgeon at the time of brachytherapy. There were 30 T1 tumors, 61 T2, and 9 T3. Segmental mastectomy was followed 2 weeks later by an interstitial implant with iridium-192 sources given as initial boost dose to the tumor bed, at the time of axillary dissection. All patients received at least 20 Gy as boost dose followed by external beam radiation to a total dose of 45-50 Gy to the breast and regional nodes delivered over a period of 4-5 weeks. With a median follow-up of 7 years a total of 3 (3%) breast recurrences were detected (1/30 in T1 tumors, 2/61 in T2 tumors). Only one of the three recurrences was at the initial tumor bed. None of the nine T3 patients included in this series recurred locally. There were 4 severe complications (2 soft tissue necroses and 2 osteonecroses) occurring in 2/30 T1 and in 2/61 T2. Cosmetic results were good to excellent in 77% of the cases and fair to poor in 23%. The actuarial local control and survival probability rate were, respectively, 95% and 85% at 5 years and 93% and 73% at 10 years. Initial brachytherapy boost to a target volume accurately determined with the operating surgeon followed by subsequent external beam radiotherapy achieved excellent local control in the breast even for lesions larger than 2 cm (70% of the reported cases)
— id: 34960, year: 1995, vol: 18, page: 331, stat: Journal Article,

Inadequate adherence to radiotherapy in Latina immigrants with carcinoma of the cervix. Potential impact on disease free survival
Formenti SC; Meyerowitz BE; Ell K; Muderspach L; Groshen S; Leedham B; Klement V; Morrow PC
1995 Mar 1;75(5):1135-1140, Cancer
BACKGROUND. Radiation therapy plays an important role in the loco-regional control of carcinoma of the cervix. Strict adherence to the radiation protocol, without the introduction of time breaks, has been shown to favorably affect loco-regional control and survival, making adherence a crucial variable for optimal outcome. Because carcinoma of the cervix is a common disease among Latinas, with survival rates worse than those of other ethnic groups in this country, the pattern of adherence to the prescribed radiation treatment among Latina patients seen at Los Angeles County Hospital were studied. METHODS. The records of 69 consecutive Latina patients with cervical cancer who received radiation therapy at Los Angeles County Hospital were reviewed. Semi-structured interviews in a successive group of 30 similar patients were conducted to acquire preliminary information about their psychosocial characteristics. RESULTS. The results demonstrate inferior rates of optimal adherence to radiation treatment among Latina immigrant patients when compared with the rates reported in the literature for the general population of cervical cancer patients in United States (16 vs. 63%). Furthermore, a large subset of patients (20%) in the series elected to discontinue treatment without a medical reason. When a comparable group of Latina patients was interviewed, potential practical, psychologic, and cultural barriers to optimal care were identified. CONCLUSIONS. The results from this exploratory study support the need for further studies to document the pattern of adherence to radiotherapy in the rest of the country among this minority population. The results suggest that an intervention to improve information and adherence to radiation therapy may be necessary to assure Latinas a chance for rates of cure comparable with the national standards
— id: 34961, year: 1995, vol: 75, page: 1135, stat: Journal Article,

Surgery with adjuvant irradiation in patients with pathologic stage C adenocarcinoma of the prostate
Petrovich, Z; Lieskovsky, G; Freeman, J; Luxton, G; Groshen, S; Formenti, S; Baert, L; Chen, S C; Skinner, D G
1995 Nov 1;76(9):1621-1628, Cancer
BACKGROUND: In recent years, the routine use of prostate-specific antigen (PSA) to detect cancer of the prostate (CaP) early has renewed the controversy regarding radiotherapy versus radical prostatectomy as the superior definitive treatment. Radiotherapy alone has been reported to result in a high incidence of local recurrence, whereas on the other hand surgical treatment has resulted in a high incidence of microscopic residual tumor. The purpose of this study was to review our treatment results with radical prostatectomy followed by planned courses of postoperative irradiation in patients with pathologic Stage (PS) C disease. METHODS: From 1972 to 1989, 95 patients with CaP with PS C tumors were treated with radical prostatectomy and bilateral pelvic lymphadenectomy. Pathologic stage distribution was: C1 in 26 (27%), C2 in 37 (39%), and C3 in 32 (34%) patients. The median follow-up was 6 years. All 95 study patients received postoperative pelvic irradiation as the only adjuvant treatment. Radiotherapy treated volume included the prostatic fossa and its immediate vicinity. The RT dose ranged from 33 Gy to 61.8 Gy (median, 45 Gy). RESULTS: The overall 5- and 10-year actuarial survival rates were 94% and 73%, respectively, with the 5 and 10 year disease specific survival of 98% and 91%, respectively. Clinical and/or prostate specific antigen recurrence was 31% at 5 years and 44% at 10 years. Prostate specific antigen elevation without clinical evidence of recurrent disease was recorded in 26 (27%) patients. Seminal vesicle involvement (C3) and high Gleason's score (8-10) were the most important factors predicting recurrence. Of the 95 patients treated, 2 had pelvic recurrence alone and 1 had local and distant metastatic disease. Radiotherapy was well tolerated with no clinically important morbidity. CONCLUSION: Based on this experience, moderate dose adjuvant radiotherapy after radical prostatectomy in patients with PS C CaP is recommended
— id: 109147, year: 1995, vol: 76, page: 1621, stat: Journal Article,

Amifostine protects bone marrow from platinum compounds without altering platinum-DNA adducts in buccal cells
Formenti, S. C.; Flor-Weiss, E. Dela; Gill, I.; Jeffers, S.; Blommaert, F.; Michaels, C.; Muggia, F. M.; Den Engelse, L.
1994 ;1(6):287-291, Cellular Pharmacology
The potential cytoprotective effect of amifostine (WR2721) was studied by analysing toxicities and platinum-DNA adducts in patients with solid tumours entered into two consecutive clinical trials of carboplatin 300 mg/m-2 day 1 and cisplatin 100 mg/m-2 day 3 given without amifostine (seven patients) and with amifostine (nine patients). Haematological toxicity was reduced by amifostine: grades 2-4 granulocytopenia was observed in only 3/21 courses and thrombocytopenia was observed in only 2/21 courses compared to grades 2-4 granulocytopenia in 22128 and thrombocytopenia in 13/28 when amifostine was not added. No delay in chemotherapy administration due to haematological recovery was seen in the group treated with amifostine as opposed to the need for delay in 50% of the chemotherapy cycles (14/28) given without chemoprotectant: mean delay was 16.2 days (range 8-21 days). Within this small sample size, no differences in other toxicities or in response rates could be observed between the two treatment groups. The addition of amifostine did not decrease the extent of platinum-DNA adducts formation in buccal cells collected before and after carboplatin and cisplatin, respectively during the first cycle of therapy. Amifostine appears to diminish the myelosuppression induced by platinum compounds, although no obvious modification of platinum-DNA adduct formation in other normal tissue (buccal cells) was noted
— id: 109223, year: 1994, vol: 1, page: 287, stat: Journal Article,

Calvert's formula and high-dose carboplatin
Uziely B; Formenti SC; Watkins K; Mazumder A; Muggia FM
1994 Aug;12(8):1740-1741, Journal of clinical oncology
— id: 34962, year: 1994, vol: 12, page: 1740, stat: Journal Article,

RADIOSENSITIVITY OF SKIN FIBROBLASTS FROM PATIENTS WITH AIDS-RELATED KAPOSIS-SARCOMA
HILL, CK; FORMENTI, SC; CHAK, LY; GILL, PS; LEVINE, AM; PETROVICH, Z
1993 ;27(8):309-310, International journal of radiation oncology biology physics
— id: 109277, year: 1993, vol: 27, page: 309, stat: Journal Article,

EFFECT OF LOCAL HYPERTHERMIA ON THE PHARMACOKINETICS PKS OF INTRAPERITONEAL IP CARBOPLATIN CB CLINICAL AND PRECLINICAL STUDY
MUGGIA F; FORMENTI S C; SAPOZINK M; CHAN K K; LOS G
1992 ;33(0):501-501, Proceedings (American Association for Cancer Research)
— id: 109245, year: 1992, vol: 33, page: 501, stat: Journal Article,

Management of carcinoma of the esophagus: the role of radiotherapy
Petrovich, Z; Langholz, B; Formenti, S; Luxton, G; Astrahan, M
1991 Feb;14(1):80-86, American journal of clinical oncology
This is an analysis of treatment results over a 23-year period in 241 patients with carcinoma of the esophagus. The treatment for unresectable patients was external beam radiotherapy (EBRT) alone (mean dose 55 Gy) in 137 (57%) combined with brachytherapy (mean dose 50 + 40 Gy) in 46 (19%), and chemotherapy alone in 3 (1%) patients. In the 55 resectable patients, treatment was resection alone in 9 (4%), and combined with radiotherapy (mean dose 43 Gy) in 46 (19%) patients. The 1-, 2-, and 5-year survival for the 241 patients was 36, 15, and 5%, respectively (median 38 weeks). The 5-year survival was 18% for radiotherapy (RT)-surgery (S) patients, 11% for EBRT with brachytherapy, 2% for EBRT alone, and 0% for patients who had S alone, p less than 0.001. Survival correlated well with initial performance status, treatment, stage of disease, tumor size, radiation dose, and degree of response, p less than 0.001, but not with tumor location in the esophagus and patients' race and sex, p = 0.44. Serious complications occurred in 5 (2%) patients treated with RT alone and in 4 (7%) patients treated with S alone or combined with RT. The leading cause of death was persistent or recurrent tumor in the chest found in 39% patients
— id: 109143, year: 1991, vol: 14, page: 80, stat: Journal Article,

Peripheral T-cell lymphoma
Armitage JO; Greer JP; Levine AM; Weisenburger DD; Formenti SC; Bast M; Conley S; Pierson J; Linder J; Cousar JB; et al.
1989 Jan 1;63(1):158-163, Cancer
Peripheral T-cell lymphoma is the most common type of T-cell lymphoma seen in adults in the United States. Clinical data were reviewed from 134 cases of peripheral T-cell lymphoma diagnosed in three centers. The median age of the patients was 57 years (range, 4-97 years), 59% were male, and 36 patients (27%) had a history of a preceding disorder of the immune system. The tumors were grouped histologically into large cell (43%), mixed large and small cell (40%), and small cell (17%). The stage at diagnosis was I (7%), II (21%), III (22%), and IV (50%). B symptoms were present in 57%. The most frequent sites of extranodal involvement were bone marrow (35%), skin (13%), and lung (11%). Eighty patients were treated with a multiagent chemotherapy regimen with proven curative potential in aggressive non-Hodgkin's lymphomas and the remainder of the patients received less intensive chemotherapy (36 patients), radiotherapy (nine patients), or no treatment (nine patients). Fifty percent of the intensively treated patients achieved complete remission and the actuarial 4-year survival was 45%. However, the 4-year, disease-free survival in patients with Stage IV disease was only 10%. Although peripheral T-cell lymphomas appeared similar in many ways to their B-cell counterparts, disease-free survival by stage was low and patients with Stage IV disease had an especially poor outlook
— id: 34965, year: 1989, vol: 63, page: 158, stat: Journal Article,

Primary central nervous system lymphoma in AIDS. Results of radiation therapy
Formenti SC; Gill PS; Lean E; Rarick M; Meyer PR; Boswell W; Petrovich Z; Chak L; Levine AM
1989 Mar 15;63(6):1101-1107, Cancer
Primary central nervous system (CNS) lymphoma is one of the clinical presentations of the acquired immune deficiency syndrome (AIDS). Ten patients had biopsy-proven high-grade lymphomas that were confirmed by further staging as limited to the CNS. All ten patients received cranial irradiation (total dose, 2200 to 5000 cGy). Six patients demonstrated complete response (CR) of the intracranial masses at the time of repeat computed tomography (CT) scan, whereas one attained a partial response (PR). Two of the CR patients died of multiple opportunistic infections, two experienced relapse of lymphoma, and died at 7 and 16 months from diagnosis, and two were alive without evidence of disease at 8 and 14 months from diagnosis. The median survival of the whole group was 5.5 months (range, 2 to 16 months). Patients with AIDS-related primary CNS lymphoma may respond to radiation treatment; however, response duration is usually short, and survival is influenced by refractory disease or systemic opportunistic infections
— id: 34964, year: 1989, vol: 63, page: 1101, stat: Journal Article,

Primary central nervous system lymphomas
Formenti SC; Levine AM
1989 ;42(1):213-229, Cancer treatment & research
— id: 34967, year: 1989, vol: 42, page: 213, stat: Journal Article,

Primary CNS lymphomas
Formenti SC; Levine AM
Cancer chemotherapy : concepts, clinical investigations, and therapeutic advances Boston MA : Kluwer, 1989,
— id: 5311, year: 1989, vol: , page: ?, stat: Chapter,

Reactivity of a human monoclonal antibody against carcinomas and other lesions of the colon
Formenti SC; Mitchell MS; Taylor CR; Lipkin M; Jernstrom PH; Kan-Mitchell J
1989 ;28(4):296-300, Cancer immunology immunotherapy
To identify tumor-associated antigens that may be immunogenic to man, human monoclonal antibodies (human mAb) were generated by fusing nonsecreting mouse myeloma cells with lymphocytes from regional mesenteric nodes of patients with adenocarcinomas of the colon. One IgG1 human mAb, designated as 14-31-10, was identified by its reactivity against human tumor xenografts. We have studied the reactivity of mAb 14-31-10 with formalin-fixed, paraffin-embedded specimens of human colon. A total of 86 cases were studied, including normal adult and fetal colons, adenocarcinomas of the colon, and a variety of colonic inflammatory diseases and preneoplastic lesions. Intense reactivity was found in 15 of 18 adenocarcinomas of the colon, but not in 10 specimens of normal adult or 4 specimens of fetal colonic mucosa. Interestingly, in four cases of carcinoma, reactivity was also observed in histologically normal mucosa situated 10 cm or more from the primary lesion. On the other hand, no staining was detected in any of the 16 inflammatory lesions. Of the 38 preneoplastic lesions, only 6 showed staining by the mAb: 1 of 5 benign tubular adenomatous polyps, 3 of 9 villous adenomas and tubovillous polyps, 1 of 5 specimens of ulcerative colitis and 1 of 19 specimens of familial polyposis. However, the intensity of staining was only moderate in those cases. Our data, therefore, suggest that the epitope identified by the human mAb 14-31-10 shows preferential expression in preneoplastic and neoplastic lesions of the colon, and in ostensibly normal mucosa at some distance from a primary colonic carcinoma. In all instances, the staining was cytoplasmic, suggesting a cytoplasmic or internal membrane location of the target antigen. This antigen appeared to be distinct from carcinoembryonic antigen, since staining by 14-31-10 was consistently different from that of a mouse monoclonal antibody to carcinoembryonic antigen in serial sections of the same specimens. The restricted reactivity of 14-31-10 suggests its potential application in immunohistochemistry. Moreover, the epitope identified by mAb 14-31-10 may be expressed during the progression of normal mucosa to neoplasia
— id: 34968, year: 1989, vol: 28, page: 296, stat: Journal Article,

Immunophenotypic analysis of peripheral blood leukocytes at different stages of HIV infection. An analysis of asymptomatic, ARC, and AIDS populations
Formenti SC; Turner RR; de Martini RM; Boone DC; Bishop PC; Levine AM; Parker JW
1989 Sep;92(3):300-307, American journal of clinical pathology
Blood leukocytes from 51 patients with acquired immune deficiency syndrome (AIDS) or AIDS-related syndrome (ARC) were immunophenotyped with the use of monoclonal antibodies and flow cytometry. The patients were placed into four clinically defined groups: HIV-positive asymptomatic (HIV+/A, 8); persistent generalized adenopathy (14); Kaposi's sarcoma (12); and opportunistic infections (17). Immunophenotypes were compared between groups. Statistically significant differences were seen in absolute lymphocyte counts, total T-cells, helper/inducer T-cells, the helper inducer subset of CD4+ lymphocytes, the suppressor inducer subset of CD4+ lymphocytes, activated helper T-cells, and natural killer cells. CD8+ cells and subsets were not statistically different between groups, possibly obscured by large ranges, but median values suggested differences. Results indicate a pattern of increasing or decreasing numbers of certain subpopulations as HIV infection progresses
— id: 34963, year: 1989, vol: 92, page: 300, stat: Journal Article,

Human monoclonal antibodies reactive with colon carcinoma: identification by a novel screening procedure with xenografts
Kan-Mitchell J; Formenti SC; Mitchell MS
1989 ;3(1):41-49, Journal of clinical laboratory analysis
To identify tumor-associated antigens immunogenic to man, human monoclonal antibodies (MAbs) were generated by fusing regional lymph node lymphocytes (LNLs) of each of three colon adenocarcinoma patients with the M5 mouse myeloma cell line. Heterohybridomas in 19 wells secreted human immunoglobulin (Ig) for at least 60 days. To identify immunoreactive MAbs, we devised an immunohistochemical assay with xenografts of six colon tumors. Binding was visualized with a biotin-conjugated goat antihuman Ig antibody followed by an avidin-biotin-peroxidase complex. This assay detected binding with a sensitivity of 0.5 microgram/ml human Ig. Reactivity against tumor-associated antigens (TAAs) in frozen sections of the colon xenografts was detected in 14 of the 19 supernates. However, only nine (three IgGs, five IgMs and one IgA) were reactive against formalin-fixed sections, showing that formalin-fixation destroyed some but not all antigenicity. Four MAbs were cloned and tested against the entire panel of 19 xenografts. One IgM MAb reacted only against colon carcinomas, while the other three (one each of IgA, IgG and IgM) had broader reactivities. Three of the four human MAbs did not cross-react with melanomas. In summary, human regional lymph nodes contain a high proportion of B lymphocytes sensitized to the autochthonous tumor. Immunostaining of human colon tumor xenografts can readily identify human MAbs reactive with colon carcinomas
— id: 34966, year: 1989, vol: 3, page: 41, stat: Journal Article,

The importance of brachytherapy in the treatment of patients with unresectable carcinoma esophagus
Petrovich ZP; Langholz B; Formenti SC; Lam K; Luxton G; Astraham M; Tildon T
1989 ;5:201-208, Endocurietherapy/Hyperthermia oncology
— id: 109186, year: 1989, vol: 5, page: 201, stat: Journal Article,

Surgical therapy and radiotherapy for carcinoma of the esophagus. Treatment results in 195 patients
Petrovich, Z; Lam, K; Langholz, B; Formenti, S; Luxton, G; Tildon, T
1989 Oct;98(4):614-617, Journal of thoracic & cardiovascular surgery
Between 1963 and 1986, 195 patients with carcinoma of the esophagus were seen in the Department of Radiation Oncology at the University of Southern California School of Medicine. Of these 195 patients, 137 had unresectable or inoperable tumors and received radiotherapy. A combination of radiotherapy and surgical therapy was used in 46 patients, 9 patients were treated with surgery alone, and three with chemotherapy alone. Among the nonsurgical patients, 13 scored less than 50 on the Karnofsky scale, 25 had distant metastases, and 69 lost more than 10% of their body weight. The majority (94%) had squamous cell carcinoma and a few (6%) had adenocarcinoma. Fifty percent had middle esophageal lesions, 30% had lower lesions, and 20% had upper esophageal lesions. Stage I was diagnosed in 13%, II in 27%, III in 29%, and IV in 27%; the disease was not staged in 5%. The 5-year actuarial survival rate for all patients was 4% (median 32 weeks). The 5-year survival rate of the 46 patients with combination therapy was 18%, and it was 2% for the remaining 149 patients (p less than 0.001). These figures are independent of stage of disease. The 2-year survival rate by stage was as follows: I, 25%; II, 21%; III, 5%; and IV, 0% (p less than 0.001). Complete response was obtained in 18% and partial response in 41%. Complete response was dependent on the tumor stage. It was 40% for stage I disease, 23% for stage II, 11% for stage III, and 6% for stage IV disease. Similarly, a larger percentage (39%) of the 46 patients with combination surgical/radiation therapy had a complete response than of patients treated by either radiotherapy alone (n = 137, 12%) or surgery alone (n = 9, 11%). Complete response and initial performance status were important factors influencing survival (p less than 0.001). Surgery with adjuvant irradiation offered a better survival rate than radiotherapy or surgery used as single modalities. Treatment results for patients with advanced carcinoma of the esophagus remain poor
— id: 109145, year: 1989, vol: 98, page: 614, stat: Journal Article,

Peripheral blood mononuclear cell abnormalities and their relationship to clinical course in homosexual men with HIV infection
de Martini RM; Turner RR; Formenti SC; Boone DC; Bishop PC; Levine AM; Parker JW
1988 Feb;46(2):258-271, Clinical immunology & immunopathology
Quantitative abnormalities of leukocyte subpopulations have been shown to correlate with clinical status in human immunodeficiency virus (HIV) infection. We have performed peripheral blood leukocyte phenotyping in 23 HIV-seropositive homosexual men, and correlated the results with clinical follow-up information. Individuals with CD4+ greater than 400/mm3 (Group 1) had less severe abnormalities in other mononuclear cell subpopulations than patients with CD4+ less than 400/mm3 (Group 2). Group 1 had decreased CD4+CDw29+ (B-cell inducer) cells, compared to HIV-seronegative homosexual controls, with normal CD4+CD45R+ (suppressor-inducer) cells, suggesting that CD4+ subpopulations are reduced at different rates. Group 2 had decreased counts for both CD4+CDw29+ and CD4+CD45R+ cells. Both groups had increased cytotoxic T cells (CD8+CD11b-), with decreased B cells and CD4+/CD8+ ratios, compared to HIV-seronegative homosexual controls. The Group 2 patients with subsequent clinical deterioration had particularly low CD4+ cells, CD4+CD45R+ cells, CD2+Ta1+ cells, and CD4+/CD8+ ratios and high CD8+CD11b- cells, compared to those with clinically stable illness. Our findings suggest that specific leukocyte subpopulations are altered differentially at various stages of HIV infection. However, the study involved only quantitative measurements of specific T- and B-cell subsets with no attempt to measure in vitro function. It is of course possible that normal numbers of cells in these subpopulations might be functionally deficient
— id: 34969, year: 1988, vol: 46, page: 258, stat: Journal Article,

Stereostatic radiosurgery for benign and malignant diseases of the brain
Petrovich ZP; Luxton G; Formenti SC; Zee CS; Yu C; Yozsef G; Apuzzo MLJ
Advances in neuro-oncology Mount Kisco NY : Futura, 1988,
— id: 5310, year: 1988, vol: , page: ?, stat: Chapter,

IMMUNOHISTOCHEMICAL REACTIVITY OF A HUMAN MONOCLONAL-ANTIBODY (HU-MAB) FROM A PATIENT WITH COLON CANCER
FORMENTI, SC; KANMITCHELL, J; JERNSTROM, P; TAYLOR, CR; MITCHELL, MS
1986 ;27(0):337-337, Proceedings (American Association for Cancer Research)
— id: 109246, year: 1986, vol: 27, page: 337, stat: Journal Article,

Initial manifestation of acquired immunodeficiency syndrome in the head and neck region
Helsper, J; Formenti, S; Levine, A
1986 Oct;152(4):403-406, American journal of surgery
Initial manifestation of AIDS in the head and neck region occurs frequently. The purpose of this report has been to alert the head and neck surgeon to the occurrence of AIDS-related lesions, their clinical characteristics, and disease outcome. Incomplete recognition of these disorders may delay appropriate diagnostic study and initiation of therapy. We have described 10 patients in whom the initial manifestation of AIDS-related malignancies occurred in the head and neck region. Six of these patients were found to have Kaposi's sarcoma, whereas four had non-Hodgkin's lymphomas. The specific clinical and pathologic aspects of the disease have been described, which represent common patterns of presentation. It is crucial to obtain an accurate social history, as well as a complete medical history from any patient suspected of having AIDS, and prompt biopsy of suspect lesions should be performed
— id: 109146, year: 1986, vol: 152, page: 403, stat: Journal Article,

Suramin antiviral therapy in the acquired immunodeficiency syndrome. Clinical, immunological, and virologic results
Levine AM; Gill PS; Cohen J; Hawkins JG; Formenti SC; Aguilar S; Meyer PR; Krailo M; Parker J; Rasheed S
1986 Jul;105(1):32-37, Annals of internal medicine
The human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) requires reverse transcriptase for viral replication. We treated 12 patients who had acquired immunodeficiency syndrome and active HTLV-III/LAV viremia with suramin, a potent competitive inhibitor of reverse transcriptase, in six weekly induction doses of 1 g, followed by weekly maintenance doses of 500 mg. Three of eleven evaluable patients had complete inhibition of viral reverse transcriptase levels, lasting at least 18 weeks in each. Two additional patients had marked reduction in reverse transcriptase activity. Nadir serum suramin levels at the end of the induction phase correlated with the level of reverse transcriptase reduction. Toxicity included hepatic transaminase elevation, fever, malaise, rash, proteinuria, paresthesias, reversible neutropenia, and adrenal insufficiency. Objective clinical improvement was documented in 1 patient, but no patient had improvement in immune function and 7 patients had recurrent opportunistic infections. Although suramin may suppress HTLV-III/LAV viremia, its significant toxicity and lack of effect on immune variables indicate that alternative therapy will be required
— id: 34970, year: 1986, vol: 105, page: 32, stat: Journal Article,

USE OF HUMAN XENOGRAFTS TO DETECT THE BINDING OF HUMAN MONOCLONAL-ANTIBODIES (MOABS) TO COLON-CARCINOMA
FORMENTI, SC; MITCHELL, MS; ROSEN, F; KEMPF, RA; IMAM, A; TAYLOR, CR; KANMITCHELL, J
1985 ;26(MAR):297-297, Proceedings (American Association for Cancer Research)
— id: 109247, year: 1985, vol: 26, page: 297, stat: Journal Article,

Controversie in tema di terapia del carcinoma polonare a piccole cellule
Formenti SC; Clerci M; Labianca R; Beretta G; Luporini G
1984 ;5:105-117, Argomenti di oncologia
— id: 109185, year: 1984, vol: 5, page: 105, stat: Journal Article,