Bernadine R Donahue, M.D.

Postoperative Intraperitoneal 5-Fluoro-2'-Deoxyuridine Added to Chemoradiation in Patients Curatively Resected (R0) for Locally Advanced Gastric and Gastroesophageal Junction Adenocarcinoma
Cohen DJ; Newman E; Iqbal S; Chang RY; Potmesil M; Ryan T; Donahue B; Chandra A; Liu M; Utate M; Hiotis S; Pachter LH; Hochster H; Muggia F
2011 Feb;19(2):478-485, Annals of surgical oncology
PURPOSE: Chemoradiation after surgery for locally advanced gastric cancer improves overall and relapse-free survival compared with observation. However, locoregional recurrences remain high. Accordingly, we instituted this pilot/feasibility study, including intraperitoneal 5-fluoro-2'-deoxyuridine (IP FUDR) as part of the treatment. METHODS: Gastric/gastroesophageal junction adenocarcinoma stage Ib-IV (M0) patients who underwent R(0) resection were eligible and had IP catheters inserted at time of surgery. IP FUDR (3 g/dose/day) was given during study days 1-3 and 15-17 before combined 5-fluorouracil, leucovorin, and external beam radiation (45 Gy). Endpoints included toxicity, completion rate, locoregional recurrence, and survival. RESULTS: Twenty-eight patients (22 men) were enrolled from 2002-2006 at two institutions; their median age was 59.5 years. After R(0) resection, a median 22 (range, 8-102) lymph nodes were examined, and 22 patients had positive nodes. AJCC stages were IB (n = 8), II (n = 10), IIIA (n = 5), IIIB (n = 1), and IV (n = 4). Full-dose IP FUDR and chemoradiation treatment was completed in 20 and 25 patients, respectively. At nearly 4-year median follow-up, 11 patients were disease-free, 5 were alive with disease, 7 were dead of disease, and 1 was dead from other cause; 4 have been lost to follow-up. Recurrences were local in one, intra-abdominal in six, distant in two, multiple sites in two, and unknown in one. The median relapse-free survival is 65.3 months, and the median overall survival has not yet been reached. CONCLUSIONS: IP FUDR before chemoradiation after R(0) gastric cancer resection is well tolerated without compromising completion of postoperative adjuvant treatment. Larger randomized trials studying IP FUDR as part of gastric cancer multidisciplinary treatment are needed to prove efficacy in reducing regional recurrence and improving survival
— id: 135531, year: 2011, vol: 19, page: 478, stat: Journal Article,

Local Control of Newly Diagnosed and Distally Recurrent, Low-Volume Brain Metastases Using Fixed Dose (20 Gy) Gamma Knife Radiosurgery
Elliott RE; Rush SC; Morsi A; Mehta N; Spriet J; Narayana A; Donahue B; Parker EC; Golfinos JG
2011 Apr;68(4):921-931, Neurosurgery
BACKGROUND:: Metastases to the brain occur in 20-30% of patients with cancer and have been identified on autopsy in as many as 50% of patients. OBJECTIVE:: To analyze the efficacy of 20 Gy gamma knife radiosurgery (GKR) as initial treatment in patients with 1 to 3 brain metastases </= 2 cm in greatest diameter. METHODS:: A retrospective analysis of 114 consecutive adults with KPS >/= 60 who received GKR for 1 to 3 brain metastases </= 2 cm in size was performed. Five patients lacked detailed follow-up and were excluded, leaving 109 for outcome analysis (34 males/75 females; median age: 61.2 years). All metastases received 20 Gy to the 50%-isodose line. RESULTS:: One hundred-nine patients underwent treatment of 164 metastases at initial GKR. Twenty-six patients (23.9%) were alive at last follow-up (median time: 29.9 months; range: 6.6 months to 7.8 years). The median overall survival was 13.8 months (range: 1 day to 7.6 years). Among the 52 patients with distant failure, 33 patients received 20 Gy to 95 new lesions. A total of 259 metastases received 20 Gy and 4 patients lacked imaging follow-up secondary to death prior to post-treatment imaging. Local failure occurred in 17 of 255 treated lesions (6.7%), yielding an overall local control rate of 93.3%. Actuarial local control at 6-, 12-, 24-, and 36-months was 96%, 93%, 89%, and 88%, respectively. Permanent neurological complications occurred in 3 patients (2.8%). CONCLUSION:: Among patients with 1 to 3 brain metastases </= 2 cm in size who have not received whole-brain radiation therapy, GKR with 20 Gy provides high rates of local control with low morbidity and excellent neurological symptom-free survival
— id: 124087, year: 2011, vol: 68, page: 921, stat: Journal Article,

Efficacy of gamma knife radiosurgery for small-volume recurrent malignant gliomas after initial radical resection
Elliott, Robert E; Parker, Erik C; Rush, Stephen C; Kalhorn, Stephen P; Moshel, Yaron A; Narayana, Ashwatha; Donahue, Bernadine; Golfinos, John G
2011 Jul-Aug;76(1-2):128-140, World neurosurgery
OBJECTIVE: To review the authors' experience with Gamma Knife radiosurgery (GKR) for small recurrent high-grade gliomas (HGGs) following prior radical resection, external-beam radiation therapy (EBRT), and chemotherapy with temozolomide (TMZ). METHODS: The authors retrospectively analyzed 26 consecutive adults (9 women and 17 men; median age 60.4 years; Karnofsky Performance Status [KPS] >/=70) who underwent GKR for recurrent HGGs from 2004-2009. Median lesion volume was 1.22 cc, and median treatment dose was 15 Gy. Pathology included glioblastoma multiforme (GBM; n = 16), anaplastic astrocytoma (AA; n = 5), and anaplastic mixed oligoastrocytoma (AMOA; n = 5). Two patients lost to follow-up were excluded from radiographic outcome analyses. RESULTS: Median overall survival (OS) for the entire cohort from the time of GKR was 13.5 months. Values for 12-month actuarial survival from time of GKR for GBM, AMOA, and AA were 37%, 20% and 80%. Local failure occurred in 9 patients (37.5%) at a median time of 5.8 months, and 18 patients (75%) experienced distant progression at a median of 4.8 months. Complications included radiation necrosis in two patients and transient worsening of hemiparesis in one patient. Multivariate hazard ratio (HR) analysis showed KPS 90 or greater, smaller tumor volumes, and increased time to recurrence after resection to be associated with longer OS following GKR. CONCLUSIONS: GKR provided good local tumor control in this group of clinically stable and predominantly high-functioning patients with small recurrent HGGs after radical resection. Meaningful survival times after GKR were seen. GKR can be considered for selected patients with recurrent HGGs
— id: 136644, year: 2011, vol: 76, page: 128, stat: Journal Article,

Incidence, timing, and treatment of new brain metastases after Gamma Knife surgery for limited brain disease: the case for reducing the use of whole-brain radiation therapy
Rush, Stephen; Elliott, Robert E; Morsi, Amr; Mehta, Nisha; Spriet, Jeri; Narayana, Ashwatha; Donahue, Bernadine; Parker, Erik C; Golfinos, John G
2011 Jul;115(1):37-48, Journal of neurosurgery
OBJECT: In this paper, the authors' goal was to analyze the incidence, timing, and treatment of new metastases following initial treatment with 20-Gy Gamma Knife surgery (GKS) alone in patients with limited brain metastases without whole-brain radiation therapy (WBRT). METHODS: A retrospective analysis of 114 consecutive adults (75 women and 34 men; median age 61 years) with KPS scores of 60 or higher who received GKS for 1-3 brain metastases </= 2 cm was performed (median lesion volume 0.35 cm(3)). Five patients lacking follow-up data were excluded from analysis. After treatment, patients underwent MR imaging at 6 weeks and every 3 months thereafter. New metastases were preferentially treated with additional GKS. Indications for WBRT included development of numerous metastases, leptomeningeal disease, or diffuse surgical-site recurrence. RESULTS: The median overall survival from GKS was 13.8 months. Excluding the 3 patients who died before follow-up imaging, 12 patients (11.3%) experienced local failure at a median of 7.4 months. Fifty-three patients (50%) developed new metastases at a median of 5 months. Six (7%) of 86 instances of new lesions were symptomatic. Most patients (67%) with distant failures were successfully treated using salvage GKS alone. Whole-brain radiotherapy was indicated in 20 patients (18.3%). Thirteen patients (11.9%) died of neurological disease. CONCLUSIONS: For patients with limited brain metastases and functional independence, 20-Gy GKS provides excellent disease control and high-functioning survival with minimal morbidity. New metastases developed in almost 50% of patients, but additional GKS was extremely effective in controlling disease. Using our algorithm, fewer than 20% of patients required WBRT, and only 12% died of progressive intracranial disease
— id: 136631, year: 2011, vol: 115, page: 37, stat: Journal Article,

Prospective neuraxis MRI surveillance reveals a high risk of leptomeningeal dissemination in diffuse intrinsic pontine glioma
Sethi, Rajni; Allen, Jeffrey; Donahue, Bernadine; Karajannis, Matthias; Gardner, Sharon; Wisoff, Jeffrey; Kunnakkat, Saroj; Mathew, Jeena; Zagzag, David; Newman, Kia; Narayana, Ashwatha
2011 Mar;102(1):121-127, Journal of neuro-oncology
Prognosis of diffuse intrinsic pontine gliomas (DIPGs) remains poor. Failure has been predominantly local, with leptomeningeal dissemination (LD) occurring in 4-33% of patients in pre-MRI era series. Routine craniospinal imaging after initial treatment may reveal other relapse patterns relapse. Sixteen consecutive pediatric patients with DIPG treated between 2006 and 2009 were retrospectively reviewed. Treatment regimens, recurrence patterns, survival, and pathologic diagnosis were recorded. Fourteen patients received involved-field radiotherapy to 54 Gy, and two patients received craniospinal irradiation for LD at presentation. Neuraxis MRI was performed at diagnosis and at 4 month intervals following radiotherapy. Fifteen patients have had progression of disease (median progression-free survival 5.0 +/- 1.2 months), and 13 patients have died (median survival 9.0 +/- 1.4 months). Local failure occurred in 12 patients (75%). LD occurred in nine patients (56%). LD was present at diagnosis in three patients, after initial staging and treatment in six patients, and during autopsy in two patients. Median overall survival was 12.0 +/- 3.3 months without LD and 8.0 +/- 2.1 months with LD (P = 0.059, log rank test). Median progression-free survival was 9.5 +/- 3.9 months without LD and 3.0 +/- 2.1 months with LD (P = 0.012, log rank test). The high incidence of LD probably reflects liberal use of spine MRI surveillance. All patients should undergo routine craniospinal imaging at diagnosis and follow-up. Central nervous system prophylaxis should be considered in future clinical trials
— id: 138150, year: 2011, vol: 102, page: 121, stat: Journal Article,

CAN SERUM AND/OR LUMBAR CSF BHCG BE USED TO MAKE OR CONFIRM A DIAGNOSIS OF CNS GERMINOMA?
Allen, Jeffrey; Donahue, Bernadine; Mathew, Jeena; Kretschmar, Cynthia; Pollack, Ian; Jakacki, Regina
2010 NOV ;12(2):83-83, Neuro-oncology
— id: 122731, year: 2010, vol: 12, page: 83, stat: Journal Article,

Neurological complications and symptom resolution following Gamma Knife surgery for brain metastases 2 cm or smaller in relation to eloquent cortices
Elliott, Robert E; Rush, Stephen; Morsi, Amr; Mehta, Nisha; Spriet, Jeri; Narayana, Ashwatha; Donahue, Bernadine; Parker, Erik C; Golfinos, John G
2010 Dec;113 Suppl:53-64, Journal of neurosurgery
OBJECT: Reports on resection of tumors in or near eloquent cortices have noted neurological complications in up to 30% of patients. This paper contains an analysis of symptom resolution and neurological morbidity following 20-Gy Gamma Knife surgery (GKS) for supratentorial brain metastases < or = 2 cm in greatest diameter. METHODS: The authors performed a retrospective analysis of 98 consecutively treated adults (33 men and 65 women with a median age of 61.4 years at the time of GKS) with Karnofsky Performance Scale score > or = 60, who underwent GKS for supratentorial brain metastases < or = 2 cm in diameter. Lesion location was classified as noneloquent (Grade I), near eloquent (Grade II), or eloquent (Grade III), in accordance with the grading system developed by the group at M. D. Anderson Cancer Center. Following treatment, the patients underwent MR imaging and clinical examinations at 6 weeks and every 3 months thereafter. RESULTS: Ninety-eight patients underwent 20-Gy GKS for 131 metastases at initial presentation and 31 patients underwent salvage 20-Gy GKS for 76 new lesions, for a total of 207 lesions (mean lesion volume 0.44 cm3). Lesions were classified as follows: Grade I, 96 (46.4%); Grade II, 51 (24.6%); and Grade III, 60 (29%). Fifteen patients (2 with Grade II and 13 with Grade III lesions) presented with deficits referable to their lesions, yielding pre-GKS deficit rates of 7.2% per lesion and 15.3% per patient. The pre-GKS deficits improved or resolved in 10 patients (66.7%) at a median time of 2.8 months and remained stable in 3 patients (20%). Two patients (13.3%) experienced worsened neurological deficits. One patient who was neurologically intact prior to treatment developed a new hemiparesis (1 of 83 patients [1.2%]). The rates of permanent neurological deterioration following GKS for Grades I, II, and III lesions were 0% (0 of 96 tumors), 2% (1 of 51), and 3.3% (2 of 60), respectively. The pre-GKS neurological deficits and larger lesions were the most significant risk factors for post-GKS neurological deterioration. CONCLUSIONS: Gamma Knife surgery performed using a 20-Gy dose provides amelioration of neurological deficits from brain metastases that are < or = 2 cm in diameter and located in or near eloquent cortices in nearly two-thirds of patients with a low incidence of morbidity. Consistent with the surgical literature, higher rates of neurological complications were observed as proximity to eloquent regions and lesion size increased. There was no neurological deterioration in patients harboring metastases in noneloquent areas
— id: 119235, year: 2010, vol: 113 Suppl, page: 53, stat: Journal Article,

A phase II study of preradiotherapy chemotherapy followed by hyperfractionated radiotherapy for newly diagnosed high-risk medulloblastoma/primitive neuroectodermal tumor: a report from the Children's Oncology Group (CCG 9931)
Allen, Jeffrey; Donahue, Bernadine; Mehta, Minesh; Miller, Douglas C; Rorke, Lucy B; Jakacki, Regina; Robertson, Patricia; Sposto, Richard; Holmes, Emi; Vezina, Gilbert; Muraszko, Karin; Puccetti, Diane; Prados, Michael; Chan, Ka-Wah
2009 Jul 15;74(4):1006-1011, International journal of radiation oncology biology physics
PURPOSE: To verify feasibility and monitor progression-free survival and overall survival in children with high-risk medulloblastoma and noncerebellar primitive neuroectodermal tumors (PNETs) treated in a Phase II study with preradiotherapy chemotherapy (CHT) followed by high-dose, hyperfractionated craniospinal radiotherapy (CSRT). METHODS AND MATERIALS: Eligibility criteria included age >3 years at diagnosis, medulloblastoma with either high M stage and/or >1.5 cm(2) postoperative residual disease, and all patients with noncerebellar PNET. Treatment was initiated with five alternating monthly cycles of CHT (A [cisplatin, cyclophosphamide, etoposide, and vincristine], B [carboplatin and etoposide], A, B, and A) followed by hyperfractionated CSRT (40 Gy) with a boost to the primary tumor (72 Gy) given in twice-daily 1-Gy fractions. RESULTS: The valid study group consisted of 124 patients whose median age at diagnosis was 7.8 years. Eighty-four patients (68%) completed the entire protocol according to study guidelines (within 9 months), and the median time to complete CSRT was 1.6 months. Major reasons for failure to complete CHT included progressive disease (17%) and toxic death (2.4%). The 5-year progression-free survival and overall survival rates were 43% +/- 5% and 52% +/- 5%, respectively. No significant differences were detected in subset analysis related to response to CHT, site of primary tumor, postoperative residual disease, or M stage. CONCLUSIONS: The feasibility of this intensive multimodality protocol was confirmed, and response to pre-RT CHT did not impact on survival. Survival data from this protocol can not be compared with data from other studies, given the protocol design
— id: 100476, year: 2009, vol: 74, page: 1006, stat: Journal Article,

Phase I/II trial of induction chemotherapy followed by concurrent chemoradiotherapy and surgery for locoregionally advanced pancreatic cancer
Marti, Jennifer L; Hochster, Howard S; Hiotis, Spiros P; Donahue, Bernadine; Ryan, Theresa; Newman, Elliot
2008 Dec;15(12):3521-3531, Annals of surgical oncology
BACKGROUND: We used a novel combination of induction chemotherapy with gemcitabine (GEM) and cisplatin (CDDP), followed by concurrent chemoradiotherapy (CCRT) with the same agents in patients with locoregionally advanced pancreatic cancer. Surgery or additional chemotherapy followed on the basis of response. METHODS: Patients with borderline resectable or locally advanced pancreatic cancer received induction weekly with GEM (1000 mg/m(2)) or CDDP (30 g/m(2)). Patients without progression of disease then underwent surgery or CCRT, including four cohorts of escalating GEM/CDDP doses combined with full-dose radiotherapy. After CCRT, patients deemed resectable underwent surgery; patients with disease that remained unresectable and that did not progress received additional GEM/CDDP for 2 months. RESULTS: A mean 76% of intended GEM dose and 75% of CDDP dose was delivered during induction (n = 26). There were three incidences of grade 4 toxicity (fever or neutropenia). After induction, five patients progressed and one patient underwent resection. Eighteen patients received CCRT, and three patients underwent resection. After CCRT, disease of 10 patients progressed, and in 5 patients, it remained unresectable without progression, and the patient received additional GEM/CDDP. Dose-limiting toxicity was at dose level IV (thrombocytopenia). Median overall and disease-specific survival was 13 months. CONCLUSION: GEM/CDDP induction chemotherapy followed by CCRT is well tolerated and rendered the disease of 4 of 26 patients resectable in this study. The recommended phase II dose for GEM and CDDP in combination with full-dose radiotherapy (5040 cGy) is 300 mg/m(2) and 10 mg/m(2) weekly for 5 weeks. Median survival in this group was 13 months. This neoadjuvant combined modality approach is both feasible and active; further studies are warranted
— id: 93218, year: 2008, vol: 15, page: 3521, stat: Journal Article,

Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma
Packer, RJ; Gajjar, A; Vezina, G; Rorke-Adams, L; Burger, PC; Robertson, PL; Bayer, L; LaFond, D; Donahue, BR; Marymont, MH; Muraszko, K; Langston, J; Sposto, R
2006 SEP 1 ;24(25):4202-4208, Journal of clinical oncology
Purpose To determine the event-free survival (EFS) and overall survival of children with average-risk medulloblastoma and treated with reduced-dose craniospinal radiotherapy (CSRT) and one of two postradiotherapy chemotherapies. Methods Four hundred twenty-one patients between 3 years and 21 years of age with nondisseminated medulloblastoma (MB) were prospectively randomly assigned to treatment with 23.4 Gy of CSRT, 55.8 Gy of posterior fossa RT, plus one of two adjuvant chemotherapy regimens: lomustine (CCNU), cisplatin, and vincristine; or cyclophosphamide, cisplatin, and vincristine. Results Forty-two of 421 patients enrolled were excluded from analysis. Sixty-six of the remaining 379 patients had incompletely assessable postoperative studies. Five-year EFS and survival for the cohort of 379 patients was 81% +/- 2.1% and 86% +/- 9%, respectively (median follow-up over 5 years). EFS was unaffected by sex, race, age, treatment regimen, brainstem involvement, or excessive anaplasia. EFS was detrimentally affected by neuroradiographic unassessability. Patients with areas of frank dissemination had a 5-year EFS of 36% +/- 15%. Sixty-seven percent of progressions had some component of dissemination. There were seven second malignancies. Infections occurred more frequently on the cyclophosphamide arm and electrolyte abnormalities were more common on the CCNU regimen. Conclusion This study discloses an encouraging EFS rate for children with nondisseminated MB treated with reduced-dose craniospinal radiation and chemotherapy. Additional, careful, step-wise reductions in CSRT in adequately staged patients may be possible
— id: 68635, year: 2006, vol: 24, page: 4202, 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,

Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children's Cancer Group
Geyer, J Russell; Sposto, Richard; Jennings, Mark; Boyett, James M; Axtell, Richard A; Breiger, David; Broxson, Emmett; Donahue, Bernadine; Finlay, Jonathan L; Goldwein, Joel W; Heier, Linda A; Johnson, Dennis; Mazewski, Claire; Miller, Douglas C; Packer, Roger; Puccetti, Diane; Radcliffe, Jerilynn; Tao, May Lin; Shiminski-Maher, Tania
2005 Oct 20;23(30):7621-7631, Journal of clinical oncology
PURPOSE: To evaluate response rate, event-free survival (EFS), and toxicity of two chemotherapeutic regimens for treatment of children younger than 36 months with malignant brain tumors and to estimate control intervals without irradiation in children with no residual tumor after initial surgery and induction chemotherapy and with delayed irradiation in patients with residual tumor or metastatic disease at diagnosis. PATIENTS AND METHODS: Patients were randomly assigned to one of two regimens of induction chemotherapy (vincristine, cisplatin, cyclophosphamide, and etoposide v vincristine, carboplatin, ifosfamide, and etoposide). Maintenance chemotherapy began after induction in children without progressive disease. Children with no residual tumors after induction therapy and no metastatic disease at diagnosis were not to receive radiation therapy unless their tumors progressed. RESULTS: Two hundred ninety-nine infants were enrolled. Forty-two percent of patients responded to induction chemotherapy. At 5 years from study entry, the EFS rate was 27% +/- 3%, and the survival rate was 43% +/- 3%. There was no significant difference between the two arms in terms of response rate or EFS. For medulloblastoma, supratentorial primitive neuroectodermal tumor, ependymoma, and rhabdoid tumors, 5-year EFS rates were 32% +/- 5%, 17% +/- 6%, and 32% +/- 6%, and 14% +/- 7%, respectively. Fifty-eight percent of patients who were alive 5 years after study entry had not received radiation therapy. CONCLUSION: Intensified induction chemotherapy resulted in a high response rate of malignant brain tumors in infants. Survival was comparable to that of previous studies, and most patients who survived did not receive radiation therapy
— id: 62482, year: 2005, vol: 23, page: 7621, stat: Journal Article,

Postoperative intraperitoneal (IP) 5'-fluoro-2'-deoxyuridine (FUDR) added to chemoradiation in patients curatively resected (RO) for locally advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma
Newman, E; Chang, RY; Potmesil, M; Donahue, B; Marcus, SG; Hiotis, SP; Iqbal, S; Ryan, T; Hochster, HS; Muggia, FM
2005 JUN 1 ;23(16):348S-348S, Journal of clinical oncology
— id: 57796, year: 2005, vol: 23, page: 348S, stat: Journal Article,

Chapter resident education
Hirsch, Ariel E; Campbell, Shannon; Donahue, Bernadine; Abramson, Sara
2004 Oct;1(10):788-788, Journal of the American College of Radiology : JACR
— id: 73577, year: 2004, vol: 1, page: 788, stat: Journal Article,

Patterns of failure in supratentorial primitive neuroectodermal tumors treated in children's cancer group study 921, a phase III combined modality study
Hong, TS; Mehta, MP; Boyett, TM; Donahue, B; Rorke, LB; Yao, MS; Zeltzer, PM
2004 SEP 1 ;60(1):204-213, International journal of radiation oncology biology physics
Purpose: To analyze the patterns of failure in patients with supratentorial primitive neuroectodermal tumors (ST-PNETs) treated with combined modality therapy in a large, randomized, multi-institutional study. Methods and Materials: A total of 44 prospectively staged patients with ST-PNET confirmed by central pathology review were treated in the Children's Cancer Group Study 921, which compared two chemoradio-therapy regimens. The patterns of initial sites of failure were analyzed. These were compared with the failure patterns of 188 children with posterior fossa (PF) PNETs treated in the same protocol. Results: The major determinant for progression-free survival was the initial metastatic stage. The 3-year progression-free survival for M0 patients was 53% +/- 8.5% compared with 14% +/- 9.4% for M+ patients. The cumulative 5-year relapse incidence was 71.4% +/- 21% for M+ patients compared with 47.5% +/- 8.6% for M0 patients. The overall failure rate for both M0 and M+ ST-PNETs was greater than that for PF-PNETs (47.5% +/- 8.6% vs. 29.3% +/- 4.7 % for M0 and 71.4% +/- 21% vs. 48.4% +/- 5.5% for M+). Failure at the primary site, either as the sole site or as a component of initial failure, was also seen more frequently in ST-PNETs than in PF-PNETs. For M0 patients, the 5-year local failure rate as a component of initial failure was 42.0% +/- 8.5% for ST-PNETs compared with 17.7% +/- 3.9% for PF-PNETs. For patients with primary tumors either in the ST or PF, the 5-year spinal axis failure rate as a component of initial failure was not significantly different statistically when compared by M stage. For M+ patients, the 5-year spinal axis failure rate as a component of initial failure was 42.9% +/- 22.8% for ST-PNETs and 34.6% +/- 5.2% for PF-PNETs. Conclusion: Despite aggressive combined modality therapy, ST-PNETs had high rates of failure, with M+ patients faring especially poorly. Both local and spinal failure rates remained high, indicating the need to maximize both local and regional/systemic therapies. Overall, these patients fared worse than those with high-risk PF-PNETs in terms of progression-free survival and failure rates. (C) 2004 Elsevier Inc
— id: 46517, year: 2004, vol: 60, page: 204, stat: Journal Article,

Importance of MR technique for stereotactic radiosurgery
Donahue, Bernadine R; Goldberg, Judith D; Golfinos, John G; Knopp, Edmond A; Comiskey, Jessica; Rush, Stephen C; Han, Kerry; Mukhi, Vandana; Cooper, Jay S
2003 Oct;5(4):268-274, Neuro-oncology
We investigated how frequently the imaging procedure we use immediately prior to radiosurgery--triple-dose gadolinium-enhanced MR performed with the patient immobilized in a nonrelocatable head frame and 1-mm-thick MPRAGE (magnetization-prepared rapid gradient echo) images (SRS3xGado)-identifies previously unrecognized cerebral metastases in patients initially imaged by conventional MR with single-dose gadolinium (1xGado). Between July 1998 and July 2000, the diagnoses established for 47 patients who underwent radio-surgical procedures for treatment of cerebral metastases at The Gamma Knife Center of New York University were based initially on the 1xGado protocol. In July 1998, we began using SRS3xGado as our routine imaging protocol in preparation for targeting lesions for radio-surgery, using triple-dose gadolinium and acquisition of contiguous 1-mm Tl-weighted axial images. Because our SRS3xGado scans sometimes unexpectedly revealed additional metastases, we sought to learn how frequently the initial 1xGado scans would underestimate the number of metastases. We therefore reviewed the number of brain metastases identified on the SRS3xGado studies and compared the results to the number found by the 1xGado protocol, which had initially identified the brain metastases. Additional metastases, ranging from 1 to 23 lesions per patient, were identified on the SRS3xGado scan in 23 of 47 patients (49%). In 57% of the 23 patients, only one additional lesion was identified. The mean time interval between the 1xGado and the SRS3xGado scans was 20.6 days (range, 4-83 days), and the number of additional lesions detected and the time interval between two scans were negatively correlated (-0.11). The number of lesions detected on the SRS3xGado was associated only with the number of lesions on the 1xGado and not with any other patient or tumor pretreatment characteristics such as age, gender, largest tumor volume on the 1xGado, or number of days between the 1xGado and the SRS3xGado or prior surgery. The identification of additional lesions with SRS3xGado MR may have implications for patients who are treated with stereotactic radiosurgery alone (without whole-brain irradiation) with single-dose gadolinium imaging, in that unidentified lesions may go untreated. As a result of these findings we continue to use and advocate SRS3xGado scans for radiosurgery
— id: 42023, year: 2003, vol: 5, page: 268, stat: Journal Article,

Detection of additional brain metastases with triple dose gadolinium for stereotactic radiosurgery imaging
Donahue, BR; Golfinos, JG; Rush, SC; Han, K; Holland, B; Cooper, JS
2001 Nov-Dec;7(6):31-, Cancer journal
— id: 27530, year: 2001, vol: 7, page: 31, stat: Journal Article,

A phase I/II study of carboplatin combined with hyperfractionated radiotherapy for brainstem gliomas
Allen, J; Siffert, J; Donahue, B; Nirenberg, A; Jakacki, R; Robertson, P; DaRosso, R; Thoron, L; Rosovsky, M; Pinto, R
1999 SEP 15 ;86(6):1064-1069, Cancer
BACKGROUND. Brainstem gliomas often respond to radiotherapy but long term disease control is exceptional. The concomitant administration of a chemotherapy agent with radiosensitizing properties such as carboplatin may increase the efficacy of radiotherapy. METHODS. A dose escalation schedule of carboplatin was devised to determine the maximum tolerated dose (MTD) of intravenous carboplatin when given on a twice-weekly schedule during a course of hyperfractionated, involved field radiotherapy (100 centigrays [cGy] twice daily to 7200 cGy). The starting dose was 20 mg/m(2) and the dose was increased by 15 mg/m(2) after every 3 patients provided no Grade 3 or 4 (according to the National Institutes of Health Common Toxicity Criteria) toxicity occurred. Magnetic resonance imaging (MRI) scans (brain and spine) were obtained before treatment and at the time of disease progression. Clinical entry criteria included an MRI scan demonstrating a diffuse intrinsic pontine tumor and a typical 2-3-month history of evolving cranial neuropathies and a gait disorder. Biopsy-confirmed evidence of a high grade glioma was required for nonpontine brain stem tumors. RESULTS. A total of 34 patients were enrolled. The median age of the patients was 7.8 years (range, 3.6-15.4 years) and the median prodrome duration was 1.5 months (range, 0.25-36 months). The MTD was 110 mg/m(2) or a total cumulative dose of 1540 mg/m(2) over 7 weeks. The dose-limiting toxicity was hematologic. The median progression free survival was 8 months (range, 0-104+ months) and the overall survival was 12 months (range, 5-104+ months). At last follow-up there were 5 long term survivors (15%) who remained in continuous remission after a mean follow-up period of 79 months (range, 46-104 months). Fifteen of the 29 patients (52%) with recurrence and or disease progression developed leptomeningeal/intraaxial tumor spread beyond the local radiation field. CONCLUSIONS. The cumulative MTD for carboplatin is 1540 mg/m(2) when administered concomitantly with involved field, hyperfractionated radiotherapy in a twice-weekly schedule for 7 weeks. Subsequent Phase II and III clinical trials can be conducted safely at this level. (C) 1999 American Cancer Society
— id: 53957, year: 1999, vol: 86, page: 1064, stat: Journal Article,

Multiple myeloma of an extremity: must the entire bone be treated?
Catell D; Kogen Z; Donahue B; Steinfeld A
1998 Jan 1;40(1):117-119, International journal of radiation oncology biology physics
PURPOSE/OBJECTIVE: Radiation of the entire shaft of a long bone affected by multiple myeloma (MM) is often advocated to prevent recurrent disease in the bone remote from the symptomatic site. Our standard of care has been to irradiate only the symptomatic area. We investigated the pattern of recurrence in patients treated in this manner. METHODS AND MATERIALS: 163 patient with MM were treated between 1971 and 1994. Twenty-seven patients received treatment to a long bone with 41 sites irradiated (17 humeri, 22 femurs, 1 radius, 1 ulna). The most common long bone treated was the femur. All patients were treated with megavoltage therapy. The symptomatic lesion, plus a margin of 1-2 cm was treated with no attempt to treat the entire shaft. Mean radiation dose was 27.82 Gy (range 6.00-44.80 Gy). The length of the field was measured in centimeters and expressed as both an absolute (AL) and relative (RL) length (i.e., percentage of total length of bone). RESULTS: The mean total AL and RL for femur fields was 18 cm and 42%, respectively. For the humerus, the AL and RL were 20 cm and 68%, respectively. Only four patients developed progressive disease in the same bone but outside the previously irradiated field. In three of the four patients the RL was between 20 and 30%. The dose of radiation given to these patients was 12.50, 21.00, 30.00, and 35.00 Gy. In all of these four cases, treatment of progressive disease in adjacent sites provided effective palliation of symptoms. CONCLUSION: Radiation therapy to the symptomatic portion of a long bone affected by MM is effective for palliation. Symptomatic recurrence out of the irradiated field is uncommon and can be effectively treated. Potential benefits of this approach include irradiation of less normal marrow and elimination of use of pairs of fields or extended distance treatment to cover the entire femur
— id: 57114, year: 1998, vol: 40, page: 117, stat: Journal Article,

Patterns of recurrence in brain stem gliomas: evidence for craniospinal dissemination
Donahue B; Allen J; Siffert J; Rosovsky M; Pinto R
1998 Feb 1;40(3):677-680, International journal of radiation oncology biology physics
PURPOSE: The 3-year survival rate of pediatric patients with infiltrating brain stem gliomas (BSG) is < 10%. Treatment involves local field radiation, and local failure has been the hallmark of recurrence. With therapeutic advances and improved radiographic monitoring, perceived and actual patterns of failure may change. We report patterns of recurrence in a group of patients with close follow-up, treated on an institutional protocol incorporating hyperfractionated involved-field radiation therapy and concomitant carboplatin, who have been uniformly staged and treated and have undergone MRI surveillance. METHODS AND MATERIALS: From 1990-1995, 18 pediatric patients with BSG were treated on a Phase I-II trial of concurrent carboplatin and hyperfractionated radiotherapy. Eight had surgical procedures to document histology. Nine had hydrocephalus prior to death. All had pretreatment brain and spine MRIs, with and without gadolinium, that showed no other evidence of disease. Treatment consisted of 72.00 Gy involved-field hyperfractionated radiation therapy and dose-escalating concomitant carboplatin. RESULTS: Fifteen children have had progression of disease (median PFS = 9 months); and 13 have died (median OS = 14 months). Fourteen of the 15 children with progression had local failures, 8 of whom had evidence of noncontiguous spinal (4) or intracranial (7) disease documented by MRI or autopsy. One child with local control developed an intracranial metastasis. None had clinical manifestations of leptomeningeal disease. CONCLUSION: Leptomeningeal dissemination occurred within 1 month of local progression in nearly 30% of our patients and, overall, occurred in 50% prior to death. This high incidence may reflect close MRI surveillance or a changing pattern of recurrence. Because the majority of leptomeningeal disease occurs in the setting of local progression, treatment efforts must be directed primarily toward local control. However, management of leptomeningeal dissemination at recurrence is of increasing concern
— id: 57138, year: 1998, vol: 40, page: 677, stat: Journal Article,

Intracranial ependymoma in the adult patient: successful treatment with surgery and radiotherapy
Donahue B; Steinfeld A
1998 Apr;37(2):131-133, Journal of neuro-oncology
PURPOSE: Ependymoma is an uncommon intracerebral tumor in adults. Since the site of origin frequently prevents complete surgical removal, adjunctive radiotherapy is used to destroy residual disease. We present our experience in treating 10 adults with intracranial ependymoma. METHODS: Five men and 5 women were treated in the past 16 years. The median age was 38 (range 24-69). All had contrast enhanced CT or MRI showing the extent of the tumor. One patient had total excision while the remainder had subtotal removal. Radiation therapy was delivered to the tumor bed with a 1-2 cm margin of normal tissue generally at 180-200 centiGray (cGy) per treatment once a day. Total dose ranged from 5400 to 7200 cGy. Two patients received experimental treatment with 100 cGy delivered twice a day for total of 6800 and 7200 cGy respectively. Four patients received initial treatment to a large field with a subsequent boost to the tumor bed. One patient received his entire course of treatment via this large field. RESULTS: With a median follow-up of 64 months, 7 patients are alive and free of disease while 2 died of intercurrent disease, without evidence of tumor, at 7 and 9 years following treatment. Another patient died 1 1/2 years after treatment of unknown causes. CONCLUSION: We conclude that postoperative radiotherapy is effective in preventing regrowth of intracranial ependymoma following subtotal resection in adults. Treatment fields should cover the initial tumor bed with a 1-2 cm margin to avoid long term radiation damage
— id: 57137, year: 1998, vol: 37, page: 131, stat: Journal Article,

Thyroid dysfunction as a late effect in survivors of pediatric medulloblastoma/primitive neuroectodermal tumors: a comparison of hyperfractionated versus conventional radiotherapy
Chin D; Sklar C; Donahue B; Uli N; Geneiser N; Allen J; Nirenberg A; David R; Kohn B; Oberfield SE
1997 Aug 15;80(4):798-804, Cancer
BACKGROUND: Primary hypothyroidism is a common sequela of craniospinal radiotherapy in the treatment of pediatric brain tumors. METHODS: The authors compared the incidence of primary hypothyroidism after hyperfractionated radiotherapy (HFRT) (n = 14 patients) versus conventionally fractionated radiotherapy (CRT) (n = 34 patients) in a group of pediatric patients with medulloblastoma/primitive neuroectodermal tumors (MB/PNET). RESULTS: The mean age at the time of tumor diagnosis was 7.9 years in the HFRT group and 8.4 years in the CRT group. The patients were followed for a mean of 4.6 years (HFRT) and 8.3 years (CRT) after diagnosis. Mean radiation doses to the thyroid were similar in both radiotherapy groups (29 gray [Gy] [HFRT] vs. 24 Gy [CRT]). Approximately 14% of the HFRT and 62% of the CRT patients developed primary hypothyroidism within a similar period after irradiation (3.2 years [HFRT] vs. 3.0 years [CRT]). Analysis by cumulative incidence function demonstrated a significant difference in the risk of developing thyroid dysfunction between these two groups of patients (P = 0.02). CONCLUSIONS: The current study findings suggest that the use of HFRT in the treatment of pediatric patients with MB/PNET is associated with a lower risk of these patients developing primary hypothyroidism
— id: 56932, year: 1997, vol: 80, page: 798, stat: Journal Article,

Palliation of AIDS-related primary lymphoma of the brain: observations from a multi-institutional database
Corn BW; Donahue BR; Rosenstock JG; Cooper JS; Xie Y; Brandon AH; Hegde HH; Sherr DL; Fisher SA; Berson A; Han H; Abdel-Wahab M; Koprowski CD; Ruffer JE; Curran WJ Jr
1997 Jun 1;38(3):601-605, International journal of radiation oncology biology physics
PURPOSE: To catalogue the presenting symptoms of patients with AIDS who are presumed to have primary central nervous system lymphoma (PCNSL). To document the palliative efficacy of cranial irradiation (RT) relative to the endpoints of complete and overall response for the respective symptoms. METHODS: An analysis of 163 patients with AIDS-related PCNSL who were evaluated at nine urban hospitals was performed. These patients were treated for PCNSL after the establishment of a tissue diagnosis or on a presumptive basis after failing empiric treatment for toxoplasmosis. All patients were treated between 1983 and 1995 with radiotherapy (median dose-fractionation scheme = 3 Gy x 10) and steroids (>90% dexamethasone). Because multiple fractionation schemes were used, prescriptions were converted to biologically effective doses according to the formula, Gy10 = Total Dose x (1 + fractional dose/alpha-beta); using an alpha-beta value of 10. RESULTS: The overall palliative response rate for the entire group was 53%. In univariate analysis, trends were present associating complete response rates with higher performance status (KPS > or = 70 vs. KPS < or = 60 = 17% vs. 5%), female gender (women vs. men = 29% vs. 8%), and the delivery of higher biologically effective doses (BED) of RT (Gy10 > 39 vs. < or = 39 = 20% vs. 5%). In multivariate analysis of factors predicting complete response, both higher KPS and higher BED retained independent significance. A separate univariate analysis identified high performance status (KPS > or = 70 vs. KPS < or = 60 = 71% vs. 47%), and young age (< or = 35 vs. > 35 = 61% vs. 40%) as factors significantly correlating with the endpoint of the overall response. In multivariate analysis, high performance status and the delivery of higher biologically effective doses of irradiation correlated significantly with higher overall response rates. CONCLUSION: Most AIDS patients who develop symptoms from primary lymphoma of the brain can achieve some palliation from a management program that includes cranial irradiation. Young patients with excellent performance status are most likely to respond to treatment. The delivery of higher biologically effective doses of irradiation also may increase the probability of achieving a palliative response
— id: 22993, year: 1997, vol: 38, page: 601, stat: Journal Article,

Performance status and age as independent predictors of survival among AIDS patients with primary CNS lymphoma: a multivariate analysis of a multi-institutional experience
Corn BW; Donahue BR; Rosenstock JG; Hyslop T; Brandon AH; Hegde HH; Cooper JS; Sherr DL; Fisher SA; Berson A; Han H; Abdel-Wahab M; Koprowski CD; Ruffer JE; Curran WJ Jr
1997 Jan-Feb;3(1):52-56, The cancer journal of Scientific American
PURPOSE: There is limited information about the outcome of AIDS patients with primary central nervous system lymphoma treated with definitive irradiation. The purpose of this study was to determine factors associated with increased survival in such patients. METHODS: An analysis was performed of 163 patients with AIDS who were evaluated at nine urban hospitals. These patients were treated for primary central nervous system lymphoma after the establishment of a tissue diagnosis or on a presumptive basis after failing empiric treatment for toxoplasmosis. All patients were treated between 1983 and 1995 with radiotherapy (median dose-fractionation scheme = 3 Gy x 10) and steroids (> 90% dexamethasone). Because multiple fractionation schemes were used, prescriptions were converted to biologically effective dose according to the formula Gy10 = Total Dose x (1 + fractional dose/alpha-beta), using an alpha-beta of 10. RESULTS: Longer median survival times were associated with high Karnofsky performance status (KPS > or = 70 vs < or = 60: 181 vs 77 days), young age (< 35 vs > 35: 162 vs 61 days), and high total definitive irradiation doses (> 39 Gy10 vs < 39 Gy10: 162 vs 40 days). Tissue diagnosis, gender, race, number of lesions (solitary vs multiple), and the presence of other cancers did not influence outcome. In multivariate analysis, young age, high Karnofsky performance status, and the delivery of higher biologically effective doses of irradiation retained independent significance relative to the endpoint of survival. CONCLUSIONS: Even at urban tertiary medical centers, few AIDS patients with intracranial lesions undergo biopsies to establish a precise tissue diagnosis. Survival following definitive irradiation is strongly related to two pretreatment factors (young age, high performance status) and one treatment factor (total biologically effective dose of cranial radiotherapy). These variables should be considered in selecting patients for definitive irradiation and in designing future studies
— id: 36125, year: 1997, vol: 3, page: 52, stat: Journal Article,

Influence of an oligodendroglial component on the survival of patients with anaplastic astrocytomas: a report of Radiation Therapy Oncology Group 83-02
Donahue B; Scott CB; Nelson JS; Rotman M; Murray KJ; Nelson DF; Banker FL; Earle JD; Fischbach JA; Asbell SO; Gaspar LE; Markoe AM; Curran W
1997 Jul 15;38(5):911-914, International journal of radiation oncology biology physics
PURPOSE: Seven percent of patients with high grade gliomas enrolled in RTOG 83-02 had mixed astrocytoma/oligodenroglial elements on central pathology review. It has often been assumed that the most aggressive histologic component of a tumor determines biologic behavior; however in this trial, the survival of patients who had mixed glioblastomas/oligodenrogliomas was significantly longer than that of patients with pure glioblastomas (GBM). We therefore evaluated the effect of an oligodendroglial component on the survival of patients who had anaplastic astrocytomas (AAF) treated in the same trial. METHODS AND MATERIALS: One hundred nine patients who had AAF and 24 patients with mixed AAF/oligodendrogliomas (AAF/OL) were enrolled in a Phase I/II trial of randomized dose-escalation hyperfractioned radiotherapy plus BCNU. AAF/OL patients were older and more likely to have had more aggressive surgery than AAF patients. Other pretreatment characteristics were balanced between groups, as was assigned treatment. RESULTS: The median survival time for AAF was 3.0 years versus 7.3 years for AAF/OL (p = 0.019). In a multivariate analysis, adjusting for extent of surgical resection and age, an oligodendroglial component was an independent prognostic factor for survival. CONCLUSION: The results support the concept that AAFs with an oligodendroglial component have a better prognosis than pure AAF tumors, similar to the effect seen among patients with glioblastoma multiforme tumors. This better survival outcome should be taken into consideration in the design and stratification of future trials. Additionally, in contrast to patients with GBMs, patients who have AAF/OL have the potential for prolonged survival; therefore, late sequelae of treatment (both radiation and chemotherapy) must be weighed more heavily in the benefits to risks analysis
— id: 56940, year: 1997, vol: 38, page: 911, stat: Journal Article,

Tc-99m LL-2 Fab' monoclonal antibody imaging in acquired immune deficiency syndrome-related lymphoma
Kramer EL; Volm M; Donahue B; Wasserheit C; Chapnick J; Sanger J; Koslow M
1997 Dec 15;80(12 Suppl):2469-2477, Cancer
BACKGROUND: Both systemic and primary central nervous system (CNS) non-Hodgkin's lymphomas (NHL) occur in people with acquired immune deficiency syndrome (AIDS). The radiographic manifestations may be similar to other neoplasms and opportunistic infections that are also found frequently in AIDS. Furthermore, these diseases may coexist with NHL in the AIDS patient. METHODS: To evaluate the use of Tc-99m Lymphoscan (the Fab' fragment of the anti-CD-22 antibody LL-2; Immunomedics, Inc., Morris Plains, NJ) in patients with suspected AIDS lymphoma, we studied 7 patients with 35 sites of suspected disease. Six had CNS lesions suspicious for parenchymal brain lymphoma. Each patient underwent planar and single photon emission computed tomography imaging at 3-5 and 18-24 hours after administration of Lymphoscan. Scintigraphic results were compared with results of conventional diagnostic modalities. RESULTS: Overall, the sensitivity of Lymphoscan was 92% and the specificity was 86%. In brain lesions, there was 100% sensitivity and 100% specificity. Lymphoscan also had 100% sensitivity for sites of lymphomatous lymphadenopathy and for liver involvement. Although less specific in extracranial sites, Lymphoscan was correctly negative in sites of coexisting adenocarcinoma and pneumonia. Two patients had both parenchymal CNS and systemic lymphoma proven by biopsy. CONCLUSIONS: Lymphoscan appears to be a sensitive and specific method for diagnosing CNS lymphoma in AIDS patients. Although slightly less specific in extracranial sites, it may be helpful in differentiating lymphoma from other etiologies in these patients at risk for multiple neoplasms and opportunistic infections
— id: 7632, year: 1997, vol: 80, page: 2469, stat: Journal Article,

Hypothalamic-pituitary-adrenal function following cranial irradiation
Oberfield SE; Nirenberg A; Allen JC; Cohen H; Donahue B; Prasad V; Schiff R; Pang S; Ghavimi F; David R; Chrousos G; Sklar C
1997 ;47(1):9-16, Hormone research
We assessed the effect of cranial irradiation on hypothalamic-pituitary (HP)-adrenal function in 17 patients (12 females, 5 males) treated with cranial/ craniospinal irradiation for acute leukemia (2 patients) or tumors distant from the hypothalamus and pituitary (8 medulloblastoma, 3 astrocytoma, 3 rhabdomyosarcoma, 1 ependymoma). Estimated doses of radiation (RT) to the HP region ranged from 18 to 72 Gy. Thirteen of seventeen patients were also treated with chemotherapy. Patients were a median of 3.75 years of age (1.5-19 years) at diagnosis and were studied at a median of 5 years (0.1-20 years) after RT. Patients received corticotropin-releasing factor (oCRF, 1 microgram/kg i.v.), and sampling for cortisol and ACTH levels was performed at -15, 0, 15, 30, 60, 90 and 120 min. The-5- and 0-min levels were combined for a standardized baseline value (Base). Cortisol levels at 0, Base, 30 and 120 min, as well as the peak cortisol response, were significantly lower in the patients. Twelve of seventeen patients' peak cortisol levels fell below the normal range. The patients' mean integrated values for cortisol (area under the curve) were not, however, different from controls. The ACTH responses to oCRF did not differ between patients and controls. No relationship was observed between ACTH or cortisol responses and the time elapsed from treatment or dose of HP RT. Further, in 10 of 12 patients, 0-min dehydroepiandrosterone sulfate levels were lower than the expected normal mean levels for age, sex and pubertal status, and in 4 of these 10 patients the values were below the normal range. These data suggest that some patients treated with HP RT may be at risk for adrenal insufficiency
— id: 12423, year: 1997, vol: 47, page: 9, stat: Journal Article,

Hyperfractionated craniospinal radiotherapy and adjuvant chemotherapy for children with newly diagnosed medulloblastoma and other primitive neuroectodermal tumors
Allen JC; Donahue B; DaRosso R; Nirenberg A
1996 Dec 1;36(5):1155-1161, International journal of radiation oncology biology physics
PURPOSE: This single-institution Phase III study conducted from 1989 to 1995 evaluates the feasibility of a multimodality protocol combining hyperfractionated craniospinal radiotherapy (HFRT) followed by adjuvant chemotherapy in 23 patients with newly diagnosed primitive neuroectodermal tumors (PNET) arising in the central nervous system. METHODS AND MATERIALS: All 23 patients had a histologically confirmed PNET and were over 3 years of age at diagnosis. The eligibility criteria for PNET patients with cerebellar primaries (medulloblastoma) included either a high T stage (T3b or 4) or high M stage (M1-3). All patients with noncerebellar primaries were eligible regardless of T or M stage. The median age of the 23 patients was 9 years (mean 3-25); 11 were female. The primary tumor arose in the cerebellum in 19. Of these medulloblastoma patients, 15 had high T stages (T3b or T4) with large locally invasive tumors and no evidence of metastases (M0), constituting Group 1. Thirteen (86%) of these patients had gross total resections. Four other medulloblastoma patients had both high T and high M stages, constituting Group 2. Group 3 consisted of four other patients with exocerebellar primaries (two brain, one brain stem, and one cauda equina), three of whom were M3. Hyperfractionated radiotherapy was administered within 4 weeks of surgery. Twice-daily 1-Gy fractions were administered separated by 4-6 h. The total dose to the primary intracranial tumor and other areas of measurable intracranial disease was 72 Gy. The prophylactic craniospinal axis dose was 36 Gy, and boosts of 44-56 Gy were administered to metastatic spinal deposits. Following radiotherapy, monthly courses of multiagent chemotherapy were administered sequentially (cyclophosphamide-vincristine followed by cisplatin-etoposide followed by carboplatin-vincristine) for a total of 9 months. RESULTS: All patients completed radiotherapy as planned. Only three patients lost >10% of their body weight. One patient had clinically apparent radiation-induced esophagitis. The mean white blood count (WBC) nadir was 2.5/dl, and hematologic recovery occurred in all within 4 weeks of completing HFRT without the need of granulocyte-colony-stimulating factor. Two patients refused adjuvant chemotherapy, 3 patients experienced tumor progression during chemotherapy, and 2 of 18 remaining patients could not tolerate the full 9 months owing to hematologic toxicity. Of the 15 patients (93%) in Group 1, 14 remain in continuous remission for a median of 78 months, and none have died. Two of four patients in Group 2 are in continuous remission at 67 and 35 months, and two died at 18 and 30 months. One of the two patients in Group 2 who died refused adjuvant chemotherapy and developed tumor progression in the bone marrow. None of the three patients in Group 3 with evaluable disease (M3) had a complete response to therapy, and eventually all four died of progressive or recurrent disease. CONCLUSION: This multimodality protocol is feasible in the short term, and long-term monitoring of neurocognitive and neuroendocrine effects are in progress. Excellent long-term disease control has been achieved for medulloblastoma patients with high T stages who were M0 at diagnosis (Group 1), the majority of whom had gross total resections. This group has a progression-free survival of 95% after a median period of follow-up of 6.5 years. Alternative treatment strategies must be developed for patients with high M stages, as five of seven patients died of progressive or recurrent disease
— id: 12455, year: 1996, vol: 36, page: 1155, stat: Journal Article,

Neutron therapy for pancreatic cancer: Thirty years of unrealized promise
Donahue, BR; Steinfeld, AD
1996 SEP ;200(3):608-609, Radiology
— id: 52828, year: 1996, vol: 200, page: 608, stat: Journal Article,

Preirradiation chemotherapy with cyclophosphamide, doxorubicin, vincristine, and dexamethasone for primary CNS lymphomas: Initial report of Radiation Therapy Oncology Group protocol 88-06
Schultz, C; Scott, C; Sherman, W; Donahue, B; Fields, J; Murray, K; Fisher, B; Abrams, R; MeisKindblom, J
1996 FEB ;14(2):556-564, Journal of clinical oncology
Purpose: This study was a prospective phase I/II trial performed by the Radiation Therapy Oncology Group (RTOG) to test the tolerance and efficacy of preirradiation cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD) chemotherapy followed by large-volume, high-dose brain radiation therapy (Ri) for patients with primary CNS lymphoma (PCNSL). Patients and Methods: Fifty-four (52 assessable) human immunodeficiency virus (HIV)-negative patients with PCNSL were entered on study and received two (n = 20) or three (n = 32) cycles of CHOD (six patients with positive CSF cytology received intrathecal methotrexate in addition to CHOD). Whole-brain RT to 41.4 Gy and tumor boost to 18 Gy (total dose, 59.4 Gy) followed chemotherapy. Results: As of July 1994, with a minimum potential follow-up time of 20 months, 12 of 52 assessable patients remain alive without evidence of progression. The median survival time for the entire group is 16.1 months, with a 2-year survival rate of 42%. By univariate analysis, patient age was found to be a significant prognostic factor with respect to survival (P =.005) in favor of age less than 60 years, Karnofsky performance status (KPS) was of borderline significance (P =.057). Survival for patients treated on RTOG 88-06 was compared with that of patients treated on RTOG 83-15, which tested RT alone. No difference in overall survival was found (P =.53). Grade 4 neutropenia developed in 29 of 51 patients during chemotherapy, There were two deaths during chemotherapy: one as a result of sepsis and one of a pulmonary embolus. The worst toxicity during RT was less than or equal to grade 2 in 50 of 52 patients. Conclusion: preirradiation CHOD chemotherapy does not significantly improve survival over RT alone for patients with PCNSL. Age remains a powerful prognostic factor independent of therapy and must be considered in testing alternative combined approaches. (C) 1996 by American Society of Clinical Oncology
— id: 53070, year: 1996, vol: 14, page: 556, stat: Journal Article,

Delay in the diagnosis of glioblastoma multiforme: is age a factor?
Steinfeld AD; Donahue B; Walker I
1996 ;14(4):317-319, Cancer investigation
Discrimination in the delivery of health care, based on the age of the patient, is attracting increased attention. We investigated this problem by studying possible age-related delay in diagnosis in patients treated for glioblastoma multiforme (GBM). A total of 213 charts of patients with GBM seen from 1972 to 1992 were evaluated for type and duration of symptom, with 204 charts having sufficient data to be analyzed. The mean and median duration of symptoms for the entire group was 48.9 and 28 days, respectively. No age-related difference in duration of symptoms was noted. In light of the increasing incidence of GBM in patients above 60 years of age, further investigation of other possible areas of age discrimination in patients with GBM is warranted
— id: 7049, year: 1996, vol: 14, page: 317, stat: Journal Article,

Additional experience with empiric radiotherapy for presumed human immunodeficiency virus-associated primary central nervous system lymphoma
Donahue BR; Sullivan JW; Cooper JS
1995 Jul 15;76(2):328-332, Cancer
BACKGROUND. In light of the steadily improving capability to treat opportunistic infections, the authors reviewed their recent experience with short course empiric radiotherapy for the treatment of human immunodeficiency virus (HIV)-associated presumed central nervous system (CNS) lymphoma. METHODS. Medical records were reviewed of 32 previously unreported HIV-infected patients who had computed tomography and/or magnetic resonance imaging findings consistent with lymphoma, whose lesions had failed to respond to antitoxoplasmosis therapy and therefore subsequently treated with empiric radiotherapy to the cranium and meninges, nearly always 3000 cGy in 10 fractions. RESULTS. The majority of patients were in poor general condition (median Karnofsky score = 50) when radiotherapy was initiated. Fifty percent improved during or after radiation. Median survival was 2.1 months. CONCLUSIONS. Despite progress made in the past several years in the treatment of opportunistic infections and brief clinical response to radiotherapy, patients with acquired immunodeficiency syndrome who have a presumed diagnosis of CNS lymphoma continue to have extremely poor survival. Early biopsy in patients with lesions that fail to respond to empiric antitoxoplasmosis treatment or with lesions radiographically most consistent with lymphoma may improve outcome
— id: 56868, year: 1995, vol: 76, page: 328, stat: Journal Article,

Restrictive lung disease following treatment for malignant brain tumors: a potential late effect of craniospinal irradiation
Jakacki RI; Schramm CM; Donahue BR; Haas F; Allen JC
1995 Jun;13(6):1478-1485, Journal of clinical oncology
PURPOSE: To examine the effects of lomustine (CCNU), a commonly used nitrosourea, and craniospinal radiation therapy on the subsequent development of restrictive lung disease (RLD) following treatment for malignant brain tumors. PATIENTS AND METHODS: Pulmonary function testing with measurement of lung volume, spirometry, and diffusion capacity was performed in 28 patients who had received CCNU and/or radiation therapy as treatment for a malignant brain tumor. The median age at the time of treatment was 11.4 years (range, 3.9 to 36.7) and radiation therapy was completed 6 months to 11.6 years (median, 2.6 years) before testing. Patients were divided into four groups based on prior therapy. Group 1 received involved-field irradiation and a CCNU-containing chemotherapy regimen (n = 7); group 2, craniospinal irradiation with a boost to the primary tumor site and a CCNU-containing chemotherapy regimen (n = 6); group 3, craniospinal irradiation with a boost to the primary tumor site and a non-CCNU-containing chemotherapy regimen (n = 7); and group 4, craniospinal irradiation with a boost to the primary tumor site without chemotherapy (n = 8). RESULTS: Fourteen patients (50%) had findings consistent with RLD. One of seven patients (14.3%) who received CCNU without spinal irradiation had RLD, whereas 13 of 21 (61.9%) who received spinal irradiation with or without CCNU had RLD (P = .038), including four of eight patients treated with craniospinal irradiation alone. Logistic regression analysis showed that only spinal irradiation was a significant predictor for RLD. Patients who received spinal irradiation were 4.3 times more likely to have RLD than those who did not receive spinal irradiation. CONCLUSION: Spinal irradiation may be a risk factor for the development of RLD
— id: 6651, year: 1995, vol: 13, page: 1478, stat: Journal Article,

A phase II trial of preirradiation carboplatin in newly diagnosed germinoma of the central nervous system
Allen JC; DaRosso RC; Donahue B; Nirenberg A
1994 Aug 1;74(3):940-944, Cancer
BACKGROUND. Central nervous system (CNS) germinomas respond readily to both radiotherapy and chemotherapy. This study was designed to selectively reduce the dose of radiotherapy in those patients expressing a complete response (CR) to neoadjuvant carboplatin. METHODS. A Phase II trial with carboplatin was conducted in 11 newly diagnosed patients with histologically confirmed, radiologically evaluable CNS germinomas before they received radiotherapy. All patients had normal cerebrospinal fluid and serum tumor markers (i.e., human chorionic gonadotropin [HCG] and alpha fetoprotein [AFP]). Seven patients had localized tumors (three pineal, three suprasellar, and one thalamus), and four had multifocal disease. Their median age at diagnosis was 13 years (range, 7-31). One course of carboplatin consisted of 150 mg/m2 weekly for 4 consecutive weeks followed by a 2-week break. Response was evaluated after two courses. If a patient had a CR to chemotherapy, the radiotherapy doses to the involved field and the craniospinal axis were lowered from 50 Gy to 30 Gy and from 36 Gy to 21 Gy, respectively. If less than a CR was observed, two additional courses of chemotherapy were administered, after which the patient's response was reevaluated. Less than a CR required full radiotherapy doses. The radiotherapy volume was determined by the extent of disease at diagnosis (i.e., localized disease was treated with an involved field and craniospinal therapy was used for disseminated disease). RESULTS. Seven patients had a CR to carboplatin (five patients after two courses and two patients after four courses). Three patients had a partial response (one after four courses and two after two courses). The investigators of the latter two patients chose not to give additional chemotherapy. Another patient opted for radiotherapy after receiving only one course of chemotherapy and was not evaluable for response. Ten of 11 patients remain in continuous remission for a median of 25 months. One patient had a recurrence. He presented with a localized pineal germinoma and had a CR after two courses of carboplatin. He received 30 Gy of involved field radiotherapy and suffered a relapse 5 months later in multiple CNS sites. He died 23 months after diagnosis with diffuse CNS and peritoneal metastases. His serum AFP and HCG levels were elevated, consistent with a nongerminoma germ cell tumor. CONCLUSIONS. Carboplatin was highly active in treating newly diagnosed CNS germinomas. Further chemotherapy studies eventually may permit additional dose reductions and/or elimination of radiotherapy for patients with CNS germinomas
— id: 56493, year: 1994, vol: 74, page: 940, stat: Journal Article,

HYPOTHALAMIC-PITUITARY (HP)-ADRENAL FUNCTION FOLLOWING HIGH-DOSE CRANIAL IRRADIATION (RT)
OBERFIELD, S; SKLAR, C; NIRENBERG, A; ALLEN, J; GHAVIMI, F; DONAHUE, B; COHEN, H; PANG, S; DAVID, R; CHROUSOS, G
1994 APR ;35(4):A104-A104, Pediatric research
— id: 52463, year: 1994, vol: 35, page: A104, stat: Journal Article,

Short- and long-term complications of radiation therapy for pediatric brain tumors
Donahue B
1992 ;18(4):207-217, Pediatric neurosurgery
Brain tumors are the second most common malignancy of childhood after acute lymphocytic leukemia. Improvements in therapy have led to increased survival. It is estimated that by the year 2000 there will be approximately 200,000 survivors of childhood cancer. A proportion of these will have survived a central nervous system malignancy. As more children survive, complications of treatment are increasingly recognized. This paper reviews the spectrum of radiation-induced complications, both short- and long-term. Their frequency and characteristics will be reviewed as well as suggestions made to decrease their incidence
— id: 13772, year: 1992, vol: 18, page: 207, stat: Journal Article,

PROLACTIN REDUCTION AFTER COMBINED THERAPY FOR PROLACTIN MACROADENOMAS
Rush, S; Donahue, B; Cooper, P; Lee, C; Persky, M; Newall, J
1991 Apr;28(4):502-505, Neurosurgery
The ability of surgery or bromocriptine to produce endocrine control of a prolactin macroadenoma decreases as the prolactin level increases. Guidelines for the use of multimodality therapy have not been developed for tumors associated with markedly elevated prolactin levels. We reviewed the records of 21 patients with prolactin levels > 200 ng/ml treated by transsphenoidal surgery and postoperative radiotherapy with or without a dopamine agonist. Values before and after treatment were available for 19 patients (13 men and 6 women). The mean basal prolactin level before treatment for the entire group was 2410 ng/ml. Surgery and radiotherapy resulted in a 90% reduction and serum prolactin levels within normal limits in 0 of 7 patients, versus the combination of surgery, radiotherapy, and dopamine agonist, which resulted in a 99.5% reduction and values within the normal range in 12 of 12 patients. Spontaneous physiological improvement was not often observed. One woman and two men were able subsequently to have children. A plan for these patients is discussed
— id: 32187, year: 1991, vol: 28, page: 502, stat: Journal Article,

Pulmonary embolization of iodine-125 seeds following prostate implantation
Steinfeld AD; Donahue BR; Plaine L
1991 Feb;37(2):149-150, Urology
The optimal treatment of prostatic carcinoma limited to the gland remains controversial. Treatment has included implantation of Iodine-125 seeds via both a suprapubic approach and, more recently, a transperineal technique utilizing ultrasound guidance. We recently have noted a heretofore unreported complication with this latter technique, namely, embolization of seeds to the lungs. Review of the chest x-ray films of 31 patients who underwent suprapubic implants showed no evidence of this phenomenon. One of 5 patients undergoing transperineal implant was found to have seeds lodged in the lung. Complications surrounding the various treatments of localized prostate carcinoma are reviewed
— id: 14138, year: 1991, vol: 37, page: 149, stat: Journal Article,

Treatment of aggressive keratoacanthomas by radiotherapy
Donahue, B; Cooper, J S; Rush, S
1990 Sep;23(3 Pt 1):489-493, Journal of the American Academy of Dermatology
Keratoacanthomas infrequently are treated by radiotherapy. However, keratoacanthomas that are recurrent after surgical excision or whose resection would result in cosmetic deformity may benefit from radiotherapy. Between January 1970 and June 1988, 29 such keratoacanthomas in 18 patients were irradiated. Doses ranged from 3500 cGy in 15 fractions to 5600 cGy in 28 fractions. Measured end points of therapy were (1) initial response, (2) freedom from recurrence, and (3) quality of the subsequent cosmetic appearance (scored as good, fair, or poor). No lesion progressed and all eventually regressed completely. Cosmetic results generally were considered good by both the patient and the referring dermatologist; none of the results was considered poor. Our results demonstrate that radiation is an effective means of treating keratoacanthomas
— id: 141412, year: 1990, vol: 23, page: 489, stat: Journal Article,