Ashwatha Narayana, M.D.

Treatment-Related Change Versus Tumor Recurrence in High-Grade Gliomas: A Diagnostic Conundrum--Use of Dynamic Susceptibility Contrast-Enhanced (DSC) Perfusion MRI
Fatterpekar, Girish M; Galheigo, Diogo; Narayana, Ashwatha; Johnson, Glyn; Knopp, Edmond
2012 Jan;198(1):19-26, American journal of roentgenology
OBJECTIVE: The purpose of this article is to address radiation necrosis, pseudoprogression, and pseudoresponse relative to high-grade gliomas and evaluate the role of conventional MRI and, in particular, dynamic susceptibility contrast-enhanced perfusion MRI in assessing such treatment-related changes from tumor recurrence. CONCLUSION: Posttreatment imaging assessment of high-grade gliomas remains challenging. Familiarity with the expected MR imaging appearances of treatment-related change and tumor recurrence will help distinguish these entities allowing appropriate management
— id: 147218, year: 2012, vol: 198, page: 19, stat: Journal Article,

Dose to craniofacial region through portal imaging of pediatric brain tumors
Hitchen, Christine J; Osa, Etin-Osa; Dewyngaert, Keith; Chang, Jenghwa; Narayana, Ashwatha
2012 ;13(1):3385-3385, Journal of applied clinical medical physics
The purpose of this study was to determine dose to the planning target volume (PTV) and organs at risk (OARs) from portal imaging (PI) of the craniofacial region in pediatric brain tumor patients treated with intensity-modulated radiation therapy (IMRT). Twenty pediatric brain tumor patients were retrospectively studied. Each received portal imaging of treatment fields and orthogonal setup fields in the craniofacial region. The number of PI and monitor units used for PI were documented for each patient. Dose distributions and dose-volume histograms were generated to quantify the maximum, minimum, and mean dose to the PTV, and the mean dose to OARs through PI acquisition. The doses resulting from PI are reported as percentage of prescribed dose. The average maximum, minimum, and mean doses to PTV from PI were 2.9 +/- 0.7%, 2.2 +/- 1.0%, and 2.5 +/- 0.7%, respectively. The mean dose to the OARs from PI were brainstem 2.8 +/- 1.1%, optic nerves/chiasm 2.6 +/- 0.9%, cochlea 2.6 +/- 0.9%, hypothalamus/pituitary 2.4 +/- 0.6%, temporal lobes 2.3 +/- 0.6%, thyroid 1.6 +/- 0.8%, and eyes 2.6 +/- 0.9%. The mean number of portal images and the mean number of PI monitor units per patient were 58.8 and 173.3, respectively. The dose from PI while treating pediatric brain tumors using IMRT is significant (2%-3% of the prescribed dose). This may result in exceeding the tolerance limit of many critical structures and lead to unwanted late complications and secondary malignancies. Dose contributions from PI should be considered in the final documented dose. Attempts must be made in PI practices to lower the imaging dose when feasible
— id: 149810, year: 2012, vol: 13, page: 3385, 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,

TGFbeta inhibition radiosensitizes murine glioblastoma cells and decreases neurosphere-forming capacity
Hardee M.E.; Marciscano A.E.; Zagzag D.; Narayana A.; Barcellos-Hoff M.
2011 ;81(2 SUPPL 1):S714-S714, International journal of radiation oncology biology physics
S714 Purpose/Objective(s): Transforming growth factor-beta (TGFbeta) is a pleotropic cytokine in the tumor microenvironment that can promote malignant behaviors, including invasion and motility. Glioblastomas produce abundant TGFbeta, are routinely treated with radiation, and have a very poor prognosis. A role for TGFbeta in the DNA damage response has recently been discovered in which TGFb inhibition in vitro and in vivo compromises ATM-kinase activity induced by ionizing radiation (Cancer Research 66:10861-68; 62:5627-31). These data suggest that TGFbeta could protect cancer cells from the cytotoxic effects of radiation by promoting ATM dependent responses; if so, TGFbeta inhibitors, which are in clinical trials, might increase therapeutic response to radiation. Materials/Methods: We used the murine glioblastoma cell line, GL261, to test the effects of TGFbeta inhibition by LY364947 (a small molecule inhibitor of the TGFbeta type I receptor kinase) on proliferation, radiosensitivity, and neurosphere-forming capacity. Experiments were performed in triplicate and differences tested by ANOVA. Results: GL261 cells produce 0.9 ng/mL per 106 cells of total TGFbeta in media conditioned for 24 hr, the majority of which is latent TGFb2. They also respond to exogenous TGFbeta1 with an increase in Smad2 phosphorylation. Despite intact TGFb receptor kinase activity, GL261 cells displayed no growth modulation response to exogenous TGFbeta1 (0.5-2ng/mL) treatment or to inhibition by LY364947 (400nM). Nonetheless, inhibition of TGFbeta with LY364947 for 24 hours prior to radiation treatment significantly increased GL261 radiosensitivity in the clonogenic assay (p<0.001), with a 1.25 dose enhancement ratio at 10% surviving fraction. This correlated with a significant 55% decrease in H2AX foci following radiation treatment with 2Gy (p<0.0001). Irradiation of GL261 cells with 2Gy also decreased primary neurosphere-forming capacity by 28% (p<0.001, ANOVA), but had no effect on secondary neurosphere formation. Treatment with LY364947 alone had no effect on neurosphere formation. In contrast, treatment for 24 hours prior to irradiation decreased the primary neurosphere-forming capacity of irradiated GL261 cells by an additional 47% (p<0.001) and decreased secondary neurosphere formation by 68% (p<0.001). Conclusions: Given the radiosensitization and specifically the response of the neurosphere assay, which is thought to measure the glioma initiating cell population, our results suggest that inhibition of TGFb in combination with radiation represents a promising therapeutic strategy. By targeting the putative stem cells long term benefit of TGFb inhibition in glioblastoma may be achieved compared to poor response rates seen with the standard regimen of chemotherapy and radiotherapy
— id: 150892, year: 2011, vol: 81, page: S714, stat: Journal Article,

Bevacizumab in the treatment of high-grade gliomas: an overview
Kunnakkat, Saroj; Narayana, Ashwatha
2011 Dec;14(4):423-430, Angiogenesis
Angiogenesis is a process that is integral to the pathogenesis of high-grade gliomas. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor has emerged as an important therapeutic agent. Data from clinical trials in both recurrent and newly-diagnosed gliomas have shown improved radiological responses and quality of life with acceptable morbidity. However, an improvement in overall survival has not yet been seen and there are concerns on possible change in the pattern of relapse following therapy. Several unanswered questions remain including the dose, timing and sequencing that warrant further research
— id: 141485, year: 2011, vol: 14, page: 423, stat: Journal Article,

Invasion is not an independent prognostic factor in high-grade glioma
Narayana, Ashwatha; Perretta, Donato; Kunnakkat, Saroj; Gruber, Deborah; Golfinos, John; Parker, Erik; Medabalmi, Praveen; Zagzag, David; Pat Eagan, R N; Gruber, Michael
2011 Jul;7(3):331-335, Journal of cancer research & therapeutics
Purpose: The role of invasion as a prognostic factor in high-grade gliomas (HGG) remains controversial. An apparent increase in invasiveness following anti-angiogenic therapy makes this question clinically relevant. The goal of this study is to assess survival differences in patients with newly diagnosed HGG who present with diffuse invasive disease compared to those who did not, but went on to develop diffuse invasive disease following bevacizumab therapy. Materials and Methods: Twenty-three patients presented as newly diagnosed diffuse invasive HGG. All patients underwent surgical resection with radiation therapy and temozolomide for one year. Progression-free survival (PFS) and overall survival (OS) were compared to a control of 58 patients with focal high-grade glioma who received similar therapy, but that included bevacizumab at 10 mg/kg given every two weeks. Results: The patient characteristics were similar in each group. The median PFS and OS for invasive HGG patients were 6 and 13 months and for the focal HGG patients, 11 and 24 months, respectively (P=0.092 and P=0.071). In the subgroup of invasive HGG that showed significant angiogenesis, the median PFS and OS were 3 and 9 months, respectively. 56% of the focal HGG patients recurred as diffuse invasive relapse. For patients with focal HGG who recurred as invasive disease, the median PFS and OS were 9 and 21 months respectively. Conclusions: Presence of diffuse invasive disease not accompanied by angiogenesis either prior to therapy or subsequent to anti-angiogenic therapy does not seem to have prognostic significance. However, invasion accompanied by angiogenesis in newly diagnosed HGG may confer a poor prognosis
— id: 140539, year: 2011, vol: 7, page: 331, 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,

Functional MRI for radiotherapy of gliomas
Chang, Jenghwa; Narayana, Ashwatha
2010 Aug;9(4):347-358, Technology in Cancer Research & Treatment
In this paper, we review the applications of functional magnetic resonance imaging (MRI) for target delineation and critical organ avoidance for brain radiotherapy. In this article we distinguish functional MRI from brain functional MRI (fMRI). Functional MRI includes magnetic resonance spectroscopic imaging (MRSI), perfusion MRI, diffusion tensor imaging (DTI) and brain fMRI. These functional MRI modalities can provide unique metabolic, pathological and physiological information that are not available in anatomic MRI and can potentially improve the treatment outcomes of brain tumors. For example, both choline (Cho) to N-acetylaspartate (NAA) and Cho to creatine (Cr) ratios from MRSI increase with increasing tumor malignancy and can be used to grade gliomas. Relative cerebral blood volume (rCBV) measurements from dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC MRI) are superior to conventional contrast-enhanced MRI in predicting tumor biology and may be even superior to pathologic assessment in predicting patient clinical outcomes. Brain fMRI can help identify and avoid functionally critical areas when constructing treatment plans for brain radiotherapy. In the past, functional MRI measurements have not been routinely used in a clinical arena due to the experimental nature of these imaging modalities. As these methods become more commonly used and effective image co-registration algorithms become available, integration of functional MRI into the treatment process of brain radiotherapy now appears to be clinically feasible, at least in major medical centers
— id: 132193, year: 2010, vol: 9, page: 347, stat: Journal Article,

Involved-Field Radiation Therapy After Surgical Resection of Solitary Brain Metastases
Connolly, E; Parker, E; Golfino, J; Kunnakkat, S; Gruber, M; Narayana, A
2010 APR ;33(2):208-208, American journal of clinical oncology
— id: 109504, year: 2010, vol: 33, page: 208, 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,

INVASION IS AN IMPORTANT PROGNOSTIC FACTOR IN NEWLY DIAGNOSED HIGH-GRADE GLIOMAS
Kunnakkat, Saroj D.; Perretta, Donato; Medabalmi, Praveen; Gruber, Michael L.; Gruber, Deborah; Golfinos, John; Parker, Erik; Narayana, Ashwatha
2010 NOV ;12(2):5-5, Neuro-oncology
— id: 122728, year: 2010, vol: 12, page: 5, stat: Journal Article,

Teaching and Assessing Systems-Based Practice: A Pilot Course in Health Care Policy, Finance, and Law for Radiation Oncology Residents
Mitchell, James D; Parhar, Preeti; Narayana, Ashwatha
2010 ;2(3):384-388, Journal of graduate medical education
Background Under the Accreditation Council for Graduate Medical Education (ACGME) Outcome Project, residency programs are required to provide data on educational outcomes and evidence for how this information is used to improve resident education. Objective To teach and assess systems-based practice through a course in health care policy, finance, and law for radiation oncology residents, and to determine its efficacy. Methods and Materials We designed a pilot course in health care policy, finance, and law related to radiation oncology. Invited experts gave lectures on policy issues important to radiation oncology and half of the participants attended the American Society for Therapeutic Radiation and Oncology (ASTRO) Advocacy Day. Participants completed pre- and postcourse tests to assess their knowledge of health policy. Results Six radiation oncology residents participated, with 5 (84%) completing all components. For the 5 residents completing all assessments, the mean precourse score was 64% and the mean postcourse score was 84% (P=05). Improvement was noted in all 3 sections of health policy, finance, and medical law. At the end of the course, 5 of 6 residents were motivated to learn about health policy, and 4 of 6 agreed it was important for physicians to be involved in policy matters. Conclusions Teaching radiation oncology residents systems-based practice through a course on health policy, finance, and law is feasible and was well received. Such a course can help teaching programs comply with the ACGME Outcome Project and would also be applicable to trainees in other specialties
— id: 124088, year: 2010, vol: 2, page: 384, stat: Journal Article,

Change in Pattern of Relapse After Antiangiogenic Therapy in High-Grade Glioma
Narayana A; Kunnakkat SD; Medabalmi P; Golfinos J; Parker E; Knopp E; Zagzag D; Eagan P; Gruber D; Gruber ML
2010 Jan 1;82(1):77-82, International journal of radiation oncology biology physics
PURPOSE: Local recurrence is the dominant pattern of relapse in high-grade glioma (HGG) after conventional therapy. The recent use of antiangiogenic therapy has shown impressive radiologic and clinical responses in adult HGG. The preclinical data suggesting increased invasiveness after angiogenic blockade have necessitated a detailed analysis of the pattern of recurrence after therapy. METHODS AND MATERIALS: A total of 162 consecutive patients with HGG, either newly diagnosed (n = 58) or with recurrent disease (n = 104) underwent therapy with bevacizumab at 10 mg/kg every 2 weeks and conventional chemotherapy with or without involved field radiotherapy until disease progression. The pattern of recurrence and interval to progression were the primary aims of the present study. Diffuse invasive recurrence (DIR) was defined as the involvement of multiple lobes with or without crossing the midline. RESULTS: At a median follow-up of 7 months (range, 1-37), 105 patients had recurrence, and 79 patients ultimately developed DIR. The interval to progression was similar in the DIR and local recurrence groups (6.5 and 6.3 months, p = .296). The hazard risk of DIR increased exponentially with time and was similar in those with newly diagnosed and recurrent HGG (R(2) = 0.957). The duration of bevacizumab therapy increased the interval to recurrence (p < .0001) and improved overall survival (p < .0001). However, the pattern of relapse did not affect overall survival (p = .253). CONCLUSION: Along with an increase in median progression-free survival, bevacizumab therapy increased the risk of DIR in HGG patients. The risk of increased invasion with prolonged angiogenic blockade should be addressed in future clinical trials
— id: 138155, year: 2010, vol: 82, page: 77, stat: Journal Article,

INVASION AS A DOMINANT FEATURE OF FAILURE PATTERN IN HIGH-GRADE GLIOMAS FOLLOWING BEVACIZUMAB THERAPY
Narayana, Ashwatha; Kunnakkat, Saroj D.; Medabalmi, Praveen; Golfinos, John; Parker, Erik; Knopp, Edmond; Zagzag, David; Gruber, Deborah; Gruber, Michael L.
2010 NOV ;12(2):3-3, Neuro-oncology
— id: 122727, year: 2010, vol: 12, page: 3, stat: Journal Article,

Bevacizumab in recurrent high-grade pediatric gliomas
Narayana, Ashwatha; Kunnakkat, Saroj; Chacko-Mathew, Jeena; Gardner, Sharon; Karajannis, Matthias; Raza, Shahzad; Wisoff, Jeffrey; Weiner, Howard; Harter, David; Allen, Jeffrey
2010 Sep;12(9):985-990, Neuro-oncology
Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promise in treating recurrent adult high-grade glioma (HGG). However, there is very little data on recurrent or progressive pediatric HGG treated with bevacizumab. We report the results of a single institution experience using bevacizumab and irinotecan in children who relapsed or progressed following standard therapy. Twelve pediatric patients with recurrent or progressive HGG received bevacizumab at 10 mg/kg every 2 weeks with irinotecan at 125 mg/m(2). Magnetic resonance imaging (MRI) was performed prior to therapy and every 8 weeks subsequently. Ten patients had supratentorial HGG; 2 had DIPG. Radiological responses were defined according to MacDonald's criteria. Progression-free survival (PFS), overall survival (OS), and toxicities were analyzed. Ten (83.3%) patients tolerated bevacizumab without serious toxicity. Therapy was discontinued in 1 patient because of anaphylaxis. Another patient developed grade III delayed wound healing and deep vein thrombosis. Two patients (16.7%) experienced a partial response after the first MRI. No complete radiographic responses were seen. Stable disease was noted in 4 (33.3%) patients. The median PFS and OS were 2.25 and 6.25 months, respectively. A diffuse invasive recurrence pattern was noted in 5 (45.5%) patients. Treatment tolerance, toxicity, and recurrence profiles were comparable to adult HGG patients treated with bevacizumab. However, the radiological response rate, response duration, and survival appeared inferior in pediatric patients. Genetic differences in pediatric gliomas might account for this difference
— id: 111816, year: 2010, vol: 12, page: 985, stat: Journal Article,

Leptomeningeal Dissemination in Diffuse Intrinsic Pontine Gliomas, a Comparison between Magnetic Resonance Imaging and Autopsy Findings
Newman, K; Karajannis, M; Narayana, A; Allen, J; Zagzag, D
2010 FEB ;23(3):11A-11A, Modern pathology
— id: 109928, year: 2010, vol: 23, page: 11A, stat: Journal Article,

Leptomeningeal Dissemination in Diffuse Intrinsic Pontine Gliomas, a Comparison between Magnetic Resonance Imaging and Autopsy Findings
Newman, K; Karajannis, M; Narayana, A; Allen, J; Zagzag, D
2010 FEB ;90(11):11A-11A, Laboratory investigation
— id: 109947, year: 2010, vol: 90, page: 11A, 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,

Therapeutic targets in malignant glioblastoma microenvironment
Barcellos-Hoff, Mary Helen; Newcomb, Elizabeth W; Zagzag, David; Narayana, Ashwatha
2009 Jul;19(3):163-170, Seminars in radiation oncology
There is considerable evidence that the tissue microenvironment can suppress cancer and that microenvironment disruption is required for cancer growth and progression. Distortion of the microenvironment by tumor cells can promote growth, recruit nonmalignant cells that provide physiological resources, and facilitate invasion. Compared with the variable routes taken by cells to become cancers, the response of normal tissue to cancer is relatively consistent such that controlling cancer may be more readily achieved indirectly via the microenvironment. Here, we discuss 3 ideas about how the microenvironment, consisting of a vasculature, inflammatory cells, immune cells, growth factors, and extracellular matrix, might provide therapeutic targets in glioblastoma (GBM) in the context of radiotherapy (RT): (1) viable therapeutic targets exist in the GBM microenvironment, (2) RT alters the microenvironment of tissues and tumors; and (3) a potential benefit may be achieved by targeting the microenvironments induced by RT
— id: 99219, year: 2009, vol: 19, page: 163, stat: Journal Article,

A Phase II Prospective Trial of Stereotactic Radiosurgery Boost Following Surgical Resection for Brain Metastases
Beal, K; Chan, K; Chan, T; Yamada, Y; Narayana, A; Lymberis, S; Gutin, P; Tabar, V; Brennan, C
2009 NOV ;75(3):S126-S127, International journal of radiation oncology biology physics
— id: 106169, year: 2009, vol: 75, page: S126, stat: Journal Article,

Effect of MLC leaf width and PTV margin on the treatment planning of intensity-modulated stereotactic radiosurgery (IMSRS) or radiotherapy (IMSRT)
Chang, Jenghwa; Yenice, Kamil M; Jiang, Kailiu; Hunt, Margie; Narayana, Ashwatha
2009 Summer;34(2):110-116, Medical Dosimetry
We studied the effect of MLC (multileaf collimator) leaf width and PTV (planning target volume) margin on treatment planning of intensity modulated stereotactic radiosurgery (IMSRS) or radiotherapy (IMSRT). Twelve patients previously treated with IMSRS/IMSRT were retrospectively planned with 5- and 3-mm MLC leaf widths and 3- and 2-mm PTV margins using the already contoured clinical target volume and critical structures. The same beam arrangement, planning parameters, and optimization method were used in each of the 4 plans for a given patient. Each plan was normalized so that the prescription dose covered at least 99% of the PTV. Plan indices--D(mean) (mean dose), conformity index (CI), V(70) (volume receiving >or= 70% of the prescription dose), and V(50) (volume receiving >or= 50% of the prescription dose)--were calculated from the dose-volume histograms (DVHs) of the PTV, normal tissue, and organs at risk (OARs). Hypothesis testing was performed on the mean ratios of plan indices to determine the statistical significance of the relative differences. The PTV was well covered for all plans, as no significant differences were observed for D(95), V(95), D(max), D(min), and D(mean) of the PTV. The irradiated volume was approximately 23% smaller when 2-mm instead of 3-mm PTV margin was used, but it was only reduced by approximately 6% when the MLC leaf width was reduced from 5 mm to 3 mm. For normal tissue and brainstem, V(70), V(50), and D(mean) were reduced more effectively by a decrease in MLC width, while D(mean) of optic nerve and chiasm were more sensitive to a change in PTV margin. The DVH statistics for the PTV and normal structures from the treatment plan with 5-mm MLC and 2-mm PTV margin were equal to those with 3-mm MLC and 3-mm PTV margin. PTV margin reduction is more effective in sparing the normal tissue and OARs than a reduction in MLC leaf width. For IMSRS, where highly accurate setup and small PTV margins are routinely employed, the use of 5-mm MLC is therefore less desirable
— id: 106150, year: 2009, vol: 34, page: 110, stat: Journal Article,

Antiangiogenic therapy using bevacizumab in recurrent high-grade glioma: impact on local control and patient survival
Narayana, Ashwatha; Kelly, Patrick; Golfinos, John; Parker, Erik; Johnson, Glyn; Knopp, Edmond; Zagzag, David; Fischer, Ingeborg; Raza, Shahzad; Medabalmi, Praveen; Eagan, Patricia; Gruber, Michael L
2009 Jan;110(1):173-180, Journal of neurosurgery
Object Antiangiogenic agents have recently shown impressive radiological responses in high-grade glioma. However, it is not clear if the responses are related to vascular changes or due to antitumoral effects. The authors report the mature results of a clinical study of bevacizumab-based treatment of recurrent high-grade gliomas. Methods Sixty-one patients with recurrent high-grade gliomas received treatment with bevacizumab at 10 mg/kg every 2 weeks for 4 doses in an 8-week cycle along with either irinotecan or carboplatin. The choice of concomitant chemotherapeutic agent was based on the number of recurrences and prior chemotherapy. Results At a median follow-up of 7.5 months (range 1-19 months), 50 (82%) of 61 patients relapsed and 42 patients (70%) died of the disease. The median number of administered bevacizumab cycles was 2 (range 1-7 cycles). The median progression-free survival (PFS) and overall survival (OS) were 5 (95% confidence interval [CI] 2.3-7.7) and 9 (95% CI 7.6-10.4) months, respectively, as calculated from the initiation of the bevacizumab-based therapy. Radiologically demonstrated responses following therapy were noted in 73.6% of cases. Neither the choice of chemotherapeutic agent nor the performance of a resection prior to therapy had an impact on patient survival. Although the predominant pattern of relapse was local, 15 patients (30%) had diffuse disease. Conclusions Antiangiogenic therapy using bevacizumab appears to improve survival in patients with recurrent high-grade glioma. A possible change in the invasiveness of the tumor following therapy is worrisome and must be closely monitored
— id: 90721, year: 2009, vol: 110, page: 173, stat: Journal Article,

Outcomes of Stereotactic Radiosurgery in the Management of Brain Metastasis in Patients with HER2 Positive Metastatic Breast Cancer
Raza, S; Narayana, A; Morsi, A; Parker, E; Rush, S; Golfinos, J; Novik, Y
2009 DEC 15 ;69(24):874S-874S, Cancer research
— id: 106461, year: 2009, vol: 69, page: 874S, stat: Journal Article,

Feasibility study of intensity-modulated radiotherapy (IMRT) treatment planning using brain functional MRI
Chang, Jenghwa; Kowalski, Alex; Hou, Bob; Narayana, Ashwatha
2008 Spring;33(1):42-47, Medical Dosimetry
The purpose of this work was to study the feasibility of incorporating functional magnetic resonance imaging (fMRI) information for intensity modulated radiotherapy (IMRT) treatment planning of brain tumors. Three glioma patients were retrospectively replanned for radiotherapy (RT) with additional fMRI information. The fMRI of each patient was acquired using a bilateral finger-tapping paradigm with a gradient echo EPI (Echo Planer Imaging) sequence. The fMRI data were processed using the Analysis of Functional Neuroimaging (AFNI) software package for determining activation volumes, and the volumes were fused with the simulation computed tomography (CT) scan. The actived pixels in left and right primary motor cortexes (PMCs) were contoured as critical structures for IMRT planning. The goal of replanning was to minimize the RT dose to the activation volumes in the PMC regions, while maintaining a similar coverage to the planning target volume (PTV) and keeping critical structures within accepted dose tolerance. Dose-volume histograms of the treatment plans with and without considering the fMRI information were compared. Beam angles adjustment or additional beams were needed for 2 cases to meet the planning criteria. Mean dose to the contralateral and ipsilateral PMC was significantly reduced by 66% and 55%, respectively, for 1 patient. For the other 2 patients, mean dose to contralateral PMC region was lowered by 73% and 69%. In general, IMRT optimization can reduce the RT dose to the PMC regions without compromising the PTV coverage or sparing of other critical organs. In conclusion, it is feasible to incorporate the fMRI information into the RT treatment planning. IMRT planning allows a significant reduction in RT dose to the PMC regions, especially if the region does not lie within the PTV
— id: 83257, year: 2008, vol: 33, page: 42, stat: Journal Article,

Magnetic resonance spectroscopy imaging (MRSI) and brain functional magnetic resonance imaging (fMRI) for radiotherapy treatment planning of glioma
Chang, Jenghwa; Thakur, Sunitha B; Huang, Wei; Narayana, Ashwatha
2008 Oct;7(5):349-362, Technology in Cancer Research & Treatment
Conventional radiotherapy of glioma is ineffective due to uncertainties in target delineation, inadequate radiation dose, and difficulties in identifying radio-resistant high-grade tumor for dose escalation. Magnetic resonance spectroscopy imaging (MRSI) and functional magnetic resonance imaging (fMRI) provide information on altered metabolic activity of tumor cells and functionally critical brain tissues, which are not available from anatomical imaging. In this paper, we review the pathological and physiological information that might be derived from MRSI and fMRI to better delineate the treatment volume and critical organs for glioma radiotherapy. Technical difficulties for incorporating MRSI and fMRI into radiotherapy treatment planning process are discussed and potential solutions are presented. A fusion protocol is used to illustrate the feasibility of registering MRSI and fMRI with simulation CT for one glioma case. An IMRT (intensity-modulated radiotherapy) dose painting plan for this case is also presented using the fused MRSI and fMRI to delineate the clinical target volumes and Broca's area
— id: 96793, year: 2008, vol: 7, page: 349, stat: Journal Article,

Small vestibular schwannomas with no hearing: comparison of functional outcomes in stereotactic radiosurgery and microsurgery
Coelho, Daniel H; Roland, J Thomas Jr; Rush, Stephen A; Narayana, Ashwatha; St Clair, Eric; Chung, Wayne; Golfinos, John G
2008 Nov;118(11):1909-1916, Laryngoscope
OBJECTIVES: To date, numerous studies have compared functional outcomes between stereotactic radiosurgery (SRS) and microsurgery (MS) in the treatment of vestibular schwannomas (VS). However, most of them involve tumors of difference sizes, radiation dosages, and surgical approaches. Few have systematically compared issues of dysequilibrium. By studying only patients with small tumors and no hearing, we sought to minimize confounding variables. STUDY DESIGN: A retrospective chart review and telephone questionnaire. METHODS: From 1998-2006, 31 patients with small (<1.5 cm) VS and nonserviceable hearing (American Academy of Otolaryngology-Head and Neck Surgery [AAO-HNS] Class C or D) were treated at our institution. Twenty-two were available for follow-up and telephone questionnaire, including the University of California Los Angeles Dizziness Questionnaire (UCLA-DQ). Twelve underwent SRS and 10 underwent MS. All MS patients underwent the translabyrinthine approach to their tumors. Outcomes measurements included tumor control, facial nerve function, tinnitus, trigeminal function, and imbalance. RESULTS: Patients undergoing SRS had comparable rates of tumor control, facial nerve function, tinnitus, and trigeminal function to MS patients. However, SRS did result in statistically significantly worse long-term imbalance when compared with MS patients. Detailed comparisons of the two modalities are made. CONCLUSIONS: In our study population, patients with small tumors and no serviceable hearing, these data suggest that MS results in comparable minimal morbidity with SRS, though posttreatment dysequilibrium is significantly decreased. While the authors recommend translabyrinthine resection of small VS with no hearing in patients able to tolerate surgery, the need for further prospective investigation is clear
— id: 90720, year: 2008, vol: 118, page: 1909, 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,

EXPRESSION OF PHOSPHORYLATED VEGFR2 RECEPTOR IN HIGH-GRADE GLIOMAS
Fischer, I; Raza, S; Medabalmi, P; Aldape, K; Gruber, M; Narayana, A
2008 OCT ;10(5):855-856, Neuro-oncology
— id: 91328, year: 2008, vol: 10, page: 855, stat: Journal Article,

High-grade glioma before and after treatment with radiation and Avastin: initial observations
Fischer, Ingeborg; Cunliffe, Clare H; Bollo, Robert J; Raza, Shahzad; Monoky, David; Chiriboga, Luis; Parker, Erik C; Golfinos, John G; Kelly, Patrick J; Knopp, Edmond A; Gruber, Michael L; Zagzag, David; Narayana, Ashwatha
2008 Oct;10(5):700-708, Neuro-oncology
We evaluate the effects of adjuvant treatment with the angiogenesis inhibitor Avastin (bevacizumab) on pathological tissue specimens of high-grade glioma. Tissue from five patients before and after treatment with Avastin was subjected to histological evaluation and compared to four control cases of glioma before and after similar treatment protocols not including bevacizumab. Clinical and radiographic data were reviewed. Histological analysis focused on microvessel density and vascular morphology, and expression patterns of vascular endothelial growth factor-A (VEGF-A) and the hematopoietic stem cell, mesenchymal, and cell motility markers CD34, smooth muscle actin, D2-40, and fascin. All patients with a decrease in microvessel density had a radiographic response, whereas no response was seen in the patients with increased microvessel density. Vascular morphology showed apparent 'normalization' after Avastin treatment in two cases, with thin-walled and evenly distributed vessels. VEGF-A expression in tumor cells was increased in two cases and decreased in three and did not correlate with treatment response. There was a trend toward a relative increase of CD34, smooth muscle actin, D2-40, and fascin immunostaining following treatment with Avastin. Specimens from four patients with recurrent malignant gliomas before and after adjuvant treatment (not including bevacizumab) had features dissimilar from our study cases. We conclude that a change in vascular morphology can be observed following antiangiogenic treatment. There seems to be no correlation between VEGF-A expression and clinical parameters. While the phenomena we describe may not be specific to Avastin, they demonstrate the potential of tissue-based analysis for the discovery of clinically relevant treatment response biomarkers
— id: 91374, year: 2008, vol: 10, page: 700, stat: Journal Article,

Portal imaging in pediatric brain tumor patients: Are we overdoing it?
Hitchen, C; DeWyngaert, J; Narayana, A
2008 AUG ;72(1):S676-S677, International journal of radiation oncology biology physics
— id: 86799, year: 2008, vol: 72, page: S676, stat: Journal Article,

Change in pattern of relapse following anti-angiogenic therapy in high grade glioma
Narayana, A; Golfinos, JG; Raza, S; Knopp, E; Medabalmi, P; Parker, E; Kelly, P; Zagzag, D; Gruber, M
2008 AUG ;72(1):S11-S11, International journal of radiation oncology biology physics
— id: 86794, year: 2008, vol: 72, page: S11, stat: Journal Article,

Feasibility of using bevacizumab with radiation therapy and temozolomide in newly diagnosed high-grade glioma
Narayana, Ashwatha; Golfinos, John G; Fischer, Ingeborg; Raza, Shahzad; Kelly, Patrick; Parker, Erik; Knopp, Edmond A; Medabalmi, Praveen; Zagzag, David; Eagan, Patricia; Gruber, Michael L
2008 Oct 1;72(2):383-389, International journal of radiation oncology biology physics
INTRODUCTION: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has shown promise in the treatment of patients with recurrent high-grade glioma. The purpose of this study is to test the feasibility of using bevacizumab with chemoradiation in the primary management of high-grade glioma. METHODS AND MATERIALS: Fifteen patients with high-grade glioma were treated with involved field radiation therapy to a dose of 59.4 Gy at 1.8 Gy/fraction with bevacizumab 10 mg/kg on Days 14 and 28 and temozolomide 75 mg/m(2). Subsequently, bevacizumab 10 mg/kg was continued every 2 weeks with temozolomide 150 mg/m(2) for 12 months. Changes in relative cerebral blood volume, perfusion-permeability index, and tumor volume measurement were measured to assess the therapeutic response. Immunohistochemistry for phosphorylated VEGF receptor 2 (pVEGFR2) was performed. RESULTS: Thirteen patients (86.6%) completed the planned bevacizumab and chemoradiation therapy. Four Grade III/IV nonhematologic toxicities were seen. Radiographic responses were noted in 13 of 14 assessable patients (92.8%). The pVEGFR2 staining was seen in 7 of 8 patients (87.5%) at the time of initial diagnosis. Six patients have experienced relapse, 3 at the primary site and 3 as diffuse disease. One patient showed loss of pVEGFR2 expression at relapse. One-year progression-free survival and overall survival rates were 59.3% and 86.7%, respectively. CONCLUSION: Use of antiangiogenic therapy with radiation and temozolomide in the primary management of high-grade glioma is feasible. Perfusion imaging with relative cerebral blood volume, perfusion-permeability index, and pVEGFR2 expression may be used as a potential predictor of therapeutic response. Toxicities and patterns of relapse need to be monitored closely
— id: 91373, year: 2008, vol: 72, page: 383, stat: Journal Article,

Comparison of the dosimetry of spinal fields in craniospinal irradiation using two dimensional, three dimensional and intensity modulated radiation therapy planning techniques
Parhar, PK; Hitchen, C; Duckworth, T; DeWyngaert, K; Narayana, A
2008 AUG ;72(1):S211-S211, International journal of radiation oncology biology physics
— id: 86795, year: 2008, vol: 72, page: S211, stat: Journal Article,

Accuracy and feasibility of cone-beam computed tomography for stereotactic radiosurgery setup
Chang, Jenghwa; Yenice, Kamil M; Narayana, Ashwatha; Gutin, Philip H
2007 Jun;34(6):2077-2084, Medical physics
Image fusion, target localization, and setup accuracy of cone-beam computed tomography (CBCT) for stereotactic radiosurgery (SRS) were investigated in this study. A Rando head phantom rigidly attached to a stereotactic Brown-Roberts-Wells (BRW) frame was utilized to study the geometric accuracy of CBCT. Measurements of distances and angular separations between selected pairs of multiple radio-opaque targets embedded in the head phantom from a conventional simulation CT provided comparative data for geometric accuracy analysis. Localization accuracy of the CBCT scan was investigated from an analysis of BRW localization of four cylindrical objects (9 mm in diameter and 25 mm in length) independently computed from CBCT and conventional CT scans. Image fusion accuracy was quantitatively evaluated from BRW localization of multiple simulated targets from the CBCT and conventional CT scan. Finally, a CBCT setup procedure for stereotactic radiosurgery treatments was proposed and its accuracy was assessed using orthogonal target verification imaging. Our study showed that CBCT did not present any significant geometric distortions. Stereotactic coordinates of the four cylindrical objects as determined from the CBCT differed from those determined from the conventional CT on average by 0.30 mm with a standard deviation (SD) of 0.09 mm. The mean image registration accuracy of CBCT with conventional CT was 0.28 mm (SD = 0.10 mm). Setup uncertainty of our proposed CBCT setup procedure was on the same order as the conventional framed-based stereotactic systems reported in the literature (mean = 1.34 mm, SD = 0.33 mm). In conclusion, CBCT can be used to guide SRS treatment setup with accuracy comparable to the currently used frame-based stereotactic radiosurgery systems provided that intra-treatment patient motion is prevented
— id: 83245, year: 2007, vol: 34, page: 2077, stat: Journal Article,

Concurrent chemotherapy and intensity-modulated radiotherapy for locoregionally advanced laryngeal and hypopharyngeal cancers
Lee, Nancy Y; O'Meara, William; Chan, Kelvin; Della-Bianca, Cesar; Mechalakos, James G; Zhung, Joanne; Wolden, Suzanne L; Narayana, Ashwatha; Kraus, Dennis; Shah, Jatin P; Pfister, David G
2007 Oct 1;69(2):459-468, International journal of radiation oncology biology physics
PURPOSE: To perform a retrospective review of laryngeal/hypopharyngeal carcinomas treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Between January 2002 and June 2005, 20 laryngeal and 11 hypopharyngeal carcinoma patients underwent IMRT with concurrent platinum-based chemotherapy; most patients had Stage IV disease. The prescription of the planning target volume for gross, high-risk, and low-risk subclinical disease was 70, 59.4, and 54 Gy, respectively. Acute/late toxicities were retrospectively scored using the Common Toxicity Criteria scale. The 2-year local progression-free, regional progression-free, laryngectomy-free, distant metastasis-free, and overall survival rates were calculated using the Kaplan-Meier method. RESULTS: The median follow-up of the living patients was 26 months (range, 17-58 months). The 2-year local progression-free, regional progression-free, laryngectomy-free, distant metastasis-free, and overall survival rate was 86%, 94%, 89%, 92%, and 63%, respectively. Grade 2 mucositis or higher occurred in 48% of patients, and all experienced Grade 2 or higher pharyngitis during treatment. Xerostomia continued to decrease over time from the end of RT, with none complaining of Grade 2 toxicity at this analysis. The 2-year post-treatment percutaneous endoscopic gastrostomy-dependency rate for those with hypopharyngeal and laryngeal tumors was 31% and 15%, respectively. The most severe late complications were laryngeal necrosis, necrotizing fascitis, and a carotid rupture resulting in death 3 weeks after salvage laryngectomy. CONCLUSION: These preliminary results have shown that IMRT achieved encouraging locoregional control of locoregionally advanced laryngeal and hypopharyngeal carcinomas. Xerostomia improved over time. Pharyngoesophageal stricture with percutaneous endoscopic gastrostomy dependency remains a problem, particularly for patients with hypopharyngeal carcinoma and, to a lesser extent, those with laryngeal cancer. Strategies using IMRT to limit the dose delivered to the esophagus/inferior constrictor musculature without compromising target coverage might be useful to further minimize this late complication
— id: 96794, year: 2007, vol: 69, page: 459, stat: Journal Article,

Salvage re-irradiation for recurrent head and neck cancer
Lee, Nancy; Chan, Kelvin; Bekelman, Justin E; Zhung, Joanne; Mechalakos, James; Narayana, Ashwatha; Wolden, Suzanne; Venkatraman, Ennapadam S; Pfister, David; Kraus, Dennis; Shah, Jatin; Zelefsky, Michael J
2007 Jul 1;68(3):731-740, International journal of radiation oncology biology physics
PURPOSE: To present a retrospective review of treatment outcomes for recurrent head and neck (HN) cancer patients treated with re-irradiation (re-RT) at a single medical center. METHODS AND MATERIALS: From July 1996-September 2005, 105 patients with recurrent HN cancer underwent re-RT at our institution. Sites included were: the neck (n = 21), nasopharynx (n = 21), paranasal sinus (n = 18), oropharynx (n = 16), oral cavity (n = 9), larynx (n = 10), parotid (n = 6), and hypopharynx (n = 4). The median prior RT dose was 62 Gy. Seventy-five patients received chemotherapy with their re-RT (platinum-based in the majority of cases). The median re-RT dose was 59.4 Gy. In 74 (70%), re-RT utilized intensity-modulated radiation therapy (IMRT). RESULTS: With a median follow-up of 35 months, 18 patients were alive with no evidence of disease. The 2-year loco-regional progression-free survival (LRPFS) and overall survival rates were 42% and 37%, respectively. Patients who underwent IMRT, compared to those who did not, had a better 2-year LRPF (52% vs. 20%, p < 0.001). On multivariate analysis, non-nasopharynx and non-IMRT were associated with an increased risk of loco-regional (LR) failure. Patients with LR progression-free disease had better 2-year overall survival vs. those with LR failure (56% vs. 21%, p < 0.001). Acute and late Grade 3-4 toxicities were reported in 23% and 15% of patients. Severe Grade 3-4 late complications were observed in 12 patients, with a median time to development of 6 months after re-RT. CONCLUSIONS: Based on our data, achieving LR control is crucial for improved overall survival in this patient population. The use of IMRT predicted better LR tumor control. Future aggressive efforts in maximizing tumor control in the recurrent setting, including dose escalation with IMRT and improved chemotherapy, are warranted
— id: 96796, year: 2007, vol: 68, page: 731, stat: Journal Article,

Use of MR spectroscopy and functional imaging in the treatment planning of gliomas
Narayana, A; Chang, J; Thakur, S; Huang, W; Karimi, S; Hou, B; Kowalski, A; Perera, G; Holodny, A; Gutin, P H
2007 May;80(953):347-354, British journal of radiology
Routine anatomical imaging with CT and MRI does not reliably indicate the true extent or the most malignant areas of gliomas and cannot identify the functionally critical parts of the brain. The aim of the study was to see if the use of MR spectroscopic imaging (MRSI) along with functional MRI (fMRI) can better define both the target and the critical structures to be avoided to improve radiation delivery in gliomas. 12 patients with gliomas underwent multivoxel MRS and functional imaging using GE processing software. The choline to creatine ratio (Cho:Cr), which represents the degree of abnormality for each individual voxel on MRSI, was derived, converted into a grayscale grading system, fused to the MRI images and then transferred to the planning CT images. An intensity-modulated radiation therapy (IMRT) plan was developed using the dose constraints based on both the anatomical and the functionally critical regions. Cho:Cr consistently identified the gross tumour volume (GTV) within the microscopic disease (clinical target volume, CTV) and allowed dose painting using IMRT. No correlation between MRSI based Cho:Cr > or =2 and MR defined CTV nor their location was noted. However, MRSI defined Cho:Cr > or =3 was smaller by 40% compared with post-contrast T1 weighted MRI defined GTV volumes. fMRI helped in optimizing the orientation of the beams. In conclusion, both MRSI and fMRI provide additional information to conventional imaging that may guide dose painting in treatment planning of gliomas. A Phase I IMRT dose intensification trial in gliomas using this information is planned
— id: 106151, year: 2007, vol: 80, page: 347, stat: Journal Article,

Hypofractionated stereotactic radiotherapy using intensity-modulated radiotherapy in patients with one or two brain metastases
Narayana, Ashwatha; Chang, Jenghwa; Yenice, Kamil; Chan, Kelvin; Lymberis, Stella; Brennan, Cameron; Gutin, Philip H
2007 ;85(2-3):82-87, Stereotactic & functional neurosurgery
PURPOSE: A small fraction of patients with 1-2 brain metastases will not be suitable candidates to either surgical resection or stereotactic radiosurgery (SRS) due to either their location or their size. The objective of this study was to determine the local control, survival, patterns of relapse and the incidence of brain injury following a course of hypofractionated stereotactic radiotherapy while avoiding upfront whole brain radiation therapy (WBRT) in this subgroup of patients. METHODS: A Gill-Thomas removable head frame system was used for immobilization. Brain LAB software with dynamic multileaf collimator hardware was used to design and deliver an intensity-modulated radiation therapy treatment plan. A dose of 600 cGy was prescribed to the 100% isodose line that would encompass the lesion with a 3-mm margin. A total dose of 3,000 cGy was delivered in 5 fractions using 2 fractions per week. The patients were followed with neurological examination and serial MRI images done every 3 months following the procedure. RESULTS: Twenty patients have been treated using this fractionation schedule since April 2004. The 1-year local control at the site of original disease is 70%. The complete response, partial response and stable disease at the last follow-up were 15, 30 and 45%, respectively. Two patients had local recurrence at the site of original disease, while 5 had evidence of leptomeningeal disease. Two additional patients developed new brain metastases, resulting in a 1-year brain relapse-free survival of 36% following this approach. The median overall survival was 8.5 months. Three patients (15%) developed steroid dependency lasting 3 months or longer following the procedure. Four patients (20%) needed WBRT as salvage following this approach. CONCLUSIONS: The preliminary results of hypofractionated SRS are comparable to both surgery and SRS data for solitary brain metastases in terms of local control and overall survival with acceptable morbidity in this cohort of unfavorable patients
— id: 71568, year: 2007, vol: 85, page: 82, stat: Journal Article,

High-dose-rate interstitial brachytherapy in recurrent and previously irradiated head and neck cancers--preliminary results
Narayana, Ashwatha; Cohen, Gil'ad N; Zaider, Marco; Chan, Kelvin; Lee, Nancy; Wong, Richard J; Boyle, Jay; Shaha, Ashok; Kraus, Dennis; Shah, Jatin; Zelefsky, Michael J
2007 Apr-Jun;6(2):157-163, Brachytherapy
PURPOSE: Although high-dose-rate brachytherapy (HDRBT) offers significant advantages over low dose rate brachytherapy, there are scant data on improved local control (LC) and treatment-related complications in patients with recurrent head and neck (H&N) cancers. We report our preliminary results in patients with recurrent H&N cancers treated with interstitial HDRBT. METHODS AND MATERIALS: Thirty patients with recurrent H&N cancers were treated with HDRBT between September 2003 and October 2005. Seventy-seven percent (23/30) of the patients had either local or regional recurrence in the area of previous external beam radiation therapy. The treatment sites were oral cavity/oropharynx (11/30), neck (10/30), face/nasal cavity (6/30), and parotid bed (3/30). Whereas 18 patients underwent surgical resection followed by HDRBT, 3 patients were treated with combined external beam radiation and HDRBT, and the remaining 9 were treated with HDRBT alone. The dose and fractionation schedules used were 3.4Gy twice per day (b.i.d.) to 34Gy for postoperative cases, 4Gy b.i.d. to 20Gy when combined with 40-50Gy external beam, and 4Gy b.i.d. to 40Gy for definitive treatment. HDRBT was initiated 5 days after catheter placement to allow for tissue healing. RESULTS: With a median followup of 12 months, 6 local recurrences were observed 1-10 months after the procedure. The 2-year LC and overall survival outcomes for the entire group were 71% and 63%, respectively. Patients treated with surgical resection and HDRBT had an improved 2-year LC compared to the patients treated with HDRBT+/-external beam radiation alone (88% vs. 40%, p=0.05). Six Grade II and four Grade III complications were noted in five patients, all observed in the postoperative HDRBT group. CONCLUSION: The preliminary results of HDRBT indicate an acceptable LC and morbidity in recurrent H&N cancers. A planned surgical resection followed by HDRBT is associated with improved tumor control in these high-risk patients. Based on these encouraging results, prospective clinical trials are warranted using HDRBT in recurrent H&N cancers to decrease late toxicity
— id: 96795, year: 2007, vol: 6, page: 157, stat: Journal Article,

Stereotactic radiosurgery for vestibular schwannomas in patients with neurofibromatosis type 2: An analysis of tumor control, complications, and hearing preservation rates - Comments
Pollock, BE; Golfinos, JG; Roland, JT; Narayana, A; Gutin, PH; Noren, G; Chen, JCT; Goodkin, R
2007 ;60(3):468-470, Neurosurgery
— id: 105550, year: 2007, vol: 60, page: 468, stat: Journal Article,

Image-fusion of MR spectroscopic images for treatment planning of gliomas
Chang, Jenghwa; Thakur, Sunitha; Perera, Gerard; Kowalski, Alex; Huang, Wei; Karimi, Sasan; Hunt, Margie; Koutcher, Jason; Fuks, Zvi; Amols, Howard; Narayana, Ashwatha
2006 Jan;33(1):32-40, Medical physics
1H magnetic resonance spectroscopic imaging (MRSI) can improve the accuracy of target delineation for gliomas, but it lacks the anatomic resolution needed for image fusion. This paper presents a simple protocol for fusing simulation computer tomography (CT) and MRSI images for glioma intensity-modulated radiotherapy (IMRT), including a retrospective study of 12 patients. Each patient first underwent whole-brain axial fluid-attenuated-inversion-recovery (FLAIR) MRI (3 mm slice thickness, no spacing), followed by three-dimensional (3D) MRSI measurements (TE/TR: 144/1000 ms) of a user-specified volume encompassing the extent of the tumor. The nominal voxel size of MRSI ranged from 8 x 8 x 10 mm3 to 12 x 12 x 10 mm3. A system was developed to grade the tumor using the choline-to-creatine (Cho/Cr) ratios from each MRSI voxel. The merged MRSI images were then generated by replacing the Cho/Cr value of each MRSI voxel with intensities according to the Cho/Cr grades, and resampling the poorer-resolution Cho/Cr map into the higher-resolution FLAIR image space. The FUNCTOOL processing software was also used to create the screen-dumped MRSI images in which these data were overlaid with each FLAIR MRI image. The screen-dumped MRSI images were manually translated and fused with the FLAIR MRI images. Since the merged MRSI images were intrinsically fused with the FLAIR MRI images, they were also registered with the screen-dumped MRSI images. The position of the MRSI volume on the merged MRSI images was compared with that of the screen-dumped MRSI images and was shifted until agreement was within a predetermined tolerance. Three clinical target volumes (CTVs) were then contoured on the FLAIR MRI images corresponding to the Cho/Cr grades. Finally, the FLAIR MRI images were fused with the simulation CT images using a mutual-information algorithm, yielding an IMRT plan that simultaneously delivers three different dose levels to the three CTVs. The image-fusion protocol was tested on 12 (six high-grade and six low-grade) glioma patients. The average agreement of the MRSI volume position on the screen-dumped MRSI images and the merged MRSI images was 0.29 mm with a standard deviation of 0.07 mm. Of all the voxels with Cho/Cr grade one or above, the distribution of Cho/Cr grade was found to correlate with the glioma grade from pathologic finding and is consistent with literature results indicating Cho/Cr elevation as a marker for malignancy. In conclusion, an image-fusion protocol was developed that successfully incorporates MRSI information into the IMRT treatment plan for glioma
— id: 68900, year: 2006, vol: 33, page: 32, stat: Journal Article,

Intensity-modulated radiation therapy for the treatment of oropharyngeal carcinoma: the Memorial Sloan-Kettering Cancer Center experience
de Arruda, Fernando F; Puri, Dev R; Zhung, Joanne; Narayana, Ashwatha; Wolden, Suzanne; Hunt, Margie; Stambuk, Hilda; Pfister, David; Kraus, Dennis; Shaha, Ashok; Shah, Jatin; Lee, Nancy Y
2006 Feb 1;64(2):363-373, International journal of radiation oncology biology physics
PURPOSE: To review the Memorial Sloan-Kettering Cancer Center's experience in using intensity-modulated radiation therapy (IMRT) for the treatment of oropharyngeal cancer. METHODS AND MATERIALS: Between September 1998 and June 2004, 50 patients with histologically confirmed cancer of the oropharynx underwent IMRT at our institution. There were 40 men and 10 women with a median age of 56 years (range, 28-78 years). The disease was Stage I in 1 patient (2%), Stage II in 3 patients (6%), Stage III in 7 (14%), and Stage IV in 39 (78%). Forty-eight patients (96%) received definitive treatment, and 2 (4%) were treated in the postoperative adjuvant setting. Concurrent chemotherapy was used in 43 patients (86%). Patients were treated using three different IMRT approaches: 76% dose painting, 18% concomitant boost with IMRT in both am and pm deliveries, and 6% concomitant boost with IMRT only in pm delivery. Regardless of the approach, the average prescription dose to the gross tumor planning target volume was 70 Gy, while the average dose delivered to the subclinical volume was 59.4 Gy in the dose painting group and 54 Gy in the concomitant boost group. Percutaneous endoscopic gastrostomy feeding tubes (PEGs) were placed before the beginning of treatment in 84% of the patients. Acute and late toxicity were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Toxicity was also evaluated using subjective criteria such as the presence of esophageal stricture, and the need for PEG usage. The local progression-free, regional progression-free, and distant metastases-free rates, and overall survival were calculated using the Kaplan-Meier method. RESULTS: Three patients had persistent locoregional disease after treatment. The 2-year estimates of local progression-free, regional progression-free, distant metastases-free, and overall survival were 98%, 88%, 84%, and 98%, respectively. The worst acute mucositis experienced was Grade 1 in 4 patients (8%), Grade 2 in 27 (54%), and Grade 3 in 19 (38%). Xerostomia decreased with increasing time interval from the end of radiotherapy, and among the patients with at least 9 months of follow-up there was 67% Grade 0-1 and 33% Grade 2 toxicity. Of the 42 patients who required upfront PEG placement, 6 were still using PEG for nutrition at the time of this analysis. Three patients had cervical esophageal strictures, and of these, 1 was still PEG dependent 1 year after treatment. Two of these patients were treated with the IMRT concomitant boost am and pm approach, whereas the other was treated with the dose painting technique. CONCLUSIONS: Intensity-modulated radiotherapy achieved encouraging local control rates in patients with oropharyngeal carcinoma. Treatment toxicity was acceptable even in the setting of concurrent chemotherapy. Long-term follow-up is needed to confirm these preliminary findings
— id: 68904, year: 2006, vol: 64, page: 363, stat: Journal Article,

Geometric factors influencing dosimetric sparing of the parotid glands using IMRT
Hunt, Margie A; Jackson, Andrew; Narayana, Ashwatha; Lee, Nancy
2006 Sep 1;66(1):296-304, International journal of radiation oncology biology physics
PURPOSE/OBJECTIVE: To determine the relationship between the parotid volume, parotid-planning target volume (PTV) overlap, and dosimetric sparing of the parotid with intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: Parotid data were collected retrospectively for 51 patients treated with simultaneous boost IMRT. Unresectable patients received 54 or 59.4 Gy to subclinical disease, 70 Gy to gross disease. Patients treated postoperatively received 54, 60, and 66 Gy to low-risk, high-risk, and tumor bed regions. Volume and mean dose of each gland and gland segments outside of and overlapping the PTV were collected. Proximity of each gland to each PTV was recorded. RESULTS: Dosimetric sparing (mean dose <or =26.5 Gy) was achieved in 66 of 71 glands with < or =21% parotid-PTV overlap and 8 of 23 glands with >21% overlap (p = <0.0001). Among spared glands, the median mean dose in the overlap region was 55.0 Gy in glands with < or =21% overlap, but only 45.4 Gy when overlap >21%. Median mean dose was 25.9 Gy to glands overlapping PTV(54) or PTV(59) alone and 30.0 Gy to those abutting PTV(70) (p < 0.001). Although proximity to PTV(70) was associated with higher parotid dose, satisfactory sparing was achieved in 24 of 43 ipsilateral glands. CONCLUSIONS: Dosimetric sparing of the parotid is feasible when the parotid-PTV overlap is less than approximately 20%. With more overlap, sparing may result in low doses within the overlap region, possibly leading to inadequate PTV coverage. Gland proximity to the high-dose PTV is associated with higher mean dose but does not always preclude dosimetric sparing
— id: 68899, year: 2006, vol: 66, page: 296, stat: Journal Article,

A comparison of intensity-modulated radiation therapy and concomitant boost radiotherapy in the setting of concurrent chemotherapy for locally advanced oropharyngeal carcinoma
Lee, Nancy Y; de Arruda, Fernando F; Puri, Dev R; Wolden, Suzanne L; Narayana, Ashwatha; Mechalakos, James; Venkatraman, Ennapadam S; Kraus, Dennis; Shaha, Ashok; Shah, Jatin P; Pfister, David G; Zelefsky, Michael J
2006 Nov 15;66(4):966-974, International journal of radiation oncology biology physics
PURPOSE: The aim of this study was to compare toxicity/efficacy of conventional radiotherapy using delayed accelerated concomitant boost radiotherapy (CBRT) vs. intensity-modulated radiotherapy (IMRT) in the setting of concurrent chemotherapy (CT) for locally advanced oropharyngeal carcinoma. METHODS AND MATERIALS: Between September 1998 and June 2004, a total of 293 consecutive patients were treated at our institution for cancer of the oropharynx. Of these, 112 had Stage III/IV disease and squamous cell histology. In all, 41 were treated with IMRT/CT and 71 were treated with CBRT/CT, both to a median dose of 70 Gy. Most common CT was a planned two cycles given every 3 to 4 weeks of cisplatin, 100 mg/m2 i.v., but an additional cycle was given to IMRT patients when possible. Both groups were well-matched for all prognostic factors. RESULTS: Median follow-up was 46 months (range, 3-93 months) for the CBRT patients and 31 months (range, 20-64 months) for the IMRT group. Three-year actuarial local-progression-free, regional-progression-free, locoregional progression-free, distant-metastases-free, disease-free, and overall survival rates were 85% vs. 95% (p = 0.17), 95% vs. 94% (p = 0.90), 82% vs. 92% (p = 0.18), 85% vs. 86% (p = 0.78), 76% vs. 82% (p = 0.57), and 81% vs. 91% (p = 0.10) for CBRT and IMRT patients, respectively. Three patients died of treatment-related toxicity in the CBRT group vs. none undergoing IMRT. At 2 years, 4% IMRT patients vs. 21% CBRT patients were dependent on percutaneous endoscopic gastrostomy (p = 0.02). Among those who had > or =20 months follow-up, there was a significant difference in Grade > or =2 xerostomia as defined by the criteria of the Radiation Therapy and Oncology Group, 67% vs. 12% (p = 0.02), in the CBRT vs. IMRT arm. CONCLUSION: In the setting of CT for locally advanced oropharyngeal carcinoma, IMRT results in lower toxicity and similar treatment outcomes when compared with CBRT
— id: 96797, year: 2006, vol: 66, page: 966, stat: Journal Article,

Intensity-modulated radiotherapy in high-grade gliomas: clinical and dosimetric results
Narayana, Ashwatha; Yamada, Josh; Berry, Sean; Shah, Priti; Hunt, Margie; Gutin, Philip H; Leibel, Steven A
2006 Mar 1;64(3):892-897, International journal of radiation oncology biology physics
PURPOSE: To report preliminary clinical and dosimetric data from intensity-modulated radiotherapy (IMRT) for malignant gliomas. METHODS AND MATERIALS: Fifty-eight consecutive high-grade gliomas were treated between January 2001 and December 2003 with dynamic multileaf collimator IMRT, planned with the inverse approach. A dose of 59.4-60 Gy at 1.8-2.0 Gy per fraction was delivered. A total of three to five noncoplanar beams were used to cover at least 95% of the target volume with the prescription isodose line. Glioblastoma accounted for 70% of the cases, and anaplastic oligodendroglioma histology (pure or mixed) was seen in 15% of the cases. Surgery consisted of biopsy only in 26% of the patients, and 80% received adjuvant chemotherapy. RESULTS: With a median follow-up of 24 months, 85% of the patients have relapsed. The median progression-free survival time for anaplastic astrocytoma and glioblastoma histology was 5.6 and 2.5 months, respectively. The overall survival time for anaplastic glioma and glioblastoma was 36 and 9 months, respectively. Ninety-six percent of the recurrences were local. No Grade IV/V late neurologic toxicities were noted. A comparative dosimetric analysis revealed that regardless of tumor location, IMRT did not significantly improve target coverage compared with three-dimensional planning. However, IMRT resulted in a decreased maximum dose to the spinal cord, optic nerves, and eye by 16%, 7%, and 15%, respectively, owing to its improved dose conformality. The mean brainstem dose also decreased by 7%. Intensity-modulated radiotherapy delivered with a limited number of beams did not result in an increased dose to the normal brain. CONCLUSIONS: It is unlikely that IMRT will improve local control in high-grade gliomas without further dose escalation compared with conventional radiotherapy. However, it might result in decreased late toxicities associated with radiotherapy
— id: 68901, year: 2006, vol: 64, page: 892, stat: Journal Article,

Intensity-modulated stereotactic radiotherapy (IMSRT) for skull-base meningiomas
Yenice, KM; Narayana, A; Chang, J; Gutin, PH; Amols, HI
2006 ;66(4):S95-S101, International journal of radiation oncology biology physics
Purpose: To investigate the potential benefits of a micromultileaf collimator (mu MLC)-based intensity-modulated stereotactic radiotherapy (IMSRT) in skull-base meningiomas. Methods and Materials: Seven patients with inoperable or recurrent small-volume (1.7-15.5 cc) skull-base meningiomas were treated with IMSRT to 54 Gy in 30 fractions using a mu MLC in the dynamic mode. IMSRT plan quality was evaluated in comparison with the conformal stereotactic radiotherapy technique, using the same beam arrangement and static delivery with the mu MLC. Plans were compared using multiple dose distributions and dose-volume histograms for the planning target volume and organs at risk. The conformity and uniformity metrics, as well as normal-tissue complication probabilities, were calculated for the two techniques. Follow-up with MRI and clinical examination was performed at regular intervals. Results: With a mean follow-up of 17 months, local control has been achieved in all cases, and no treatment-related toxicities have been noted. For cavernous sinus tumors overlapping with optic apparatus, IMSRT has improved the dose uniformity within the target on average by 8%, which resulted in a reduction of the estimated chiasm normal-tissue complication probability by up to 65%. Conclusions: Intensity-modulated stereotactic radiotherapy can be safely delivered to improve the dose distributions in select skull-base meningiomas with an appreciable concomitant dose reduction to involved critical structures. Longer follow-up with a larger patient group is necessary to demonstrate sustained tumor control and low morbidity with IMSRT for small inoperable, recurrent, or subtotally resected meningiomas. (c) 2006 Elsevier Inc. $$:
— id: 90757, year: 2006, vol: 66, page: S95, stat: Journal Article,

Central nervous system cancers: Clinical Practice Guidelines in Oncology
Brem, Steven S; Bierman, Philip J; Black, Peter; Blumenthal, Deborah T; Brem, Henry; Chamberlain, Marc C; Chiocca, Ennio A; DeAngelis, Lisa M; Fenstermaker, Robert A; Fine, Howard A; Friedman, Allan; Glass, Jon; Grossman, Stuart A; Heimberger, Amy B; Junck, Larry; Levin, Victor; Loeffler, Jay J; Maor, Moshe H; Narayana, Ashwatha; Newton, Herbert B; Olivi, Alessandro; Portnow, Jana; Prados, Michael; Raizer, Jeffrey J; Rosenfeld, Steven S; Shrieve, Dennis C; Sills, Allen K Jr; Spence, Alexander M; Vrionis, Frank D
2005 Sep;3(5):644-690, Journal of the National Comprehensive Cancer Network : JNCCN
— id: 68902, year: 2005, vol: 3, page: 644, stat: Journal Article,

(32)P radioisotope therapy for recurrent pilocytic astrocytoma
Narayana, Ashwatha; Bhatia, Sudershan; Souweidane, Mark; Khakoo, Yasmin; Zaider, Marco
2005 ;4(2):171-173, Brachytherapy
(32)P is a pure beta-emitter that has a depth of penetration of 2-3 mm and can be useful in the treatment of cystic lesions. Its effectiveness in the treatment of a selected brain tumor is illustrated here
— id: 68905, year: 2005, vol: 4, page: 171, stat: Journal Article,

Intensity-modulated radiation therapy for the treatment of nonanaplastic thyroid cancer
Rosenbluth, Benjamin D; Serrano, Victoria; Happersett, Laura; Shaha, Ashok R; Tuttle, R Michael; Narayana, Ashwatha; Wolden, Suzanne L; Rosenzweig, Kenneth E; Chong, Lanceford M; Lee, Nancy Y
2005 Dec 1;63(5):1419-1426, International journal of radiation oncology biology physics
PURPOSE: Intensity-modulated radiation therapy (IMRT) enables highly conformal treatment for thyroid cancer (TC). In this study, we review outcomes/toxicity in a series of TC patients treated with IMRT. METHODS AND MATERIALS: Between July 2001 and January 2004, 20 nonanaplastic TC patients underwent IMRT. Mean age was 55. There were 3 T2 and 17 T4 patients. Sixteen patients had N1 disease. Seven patients had metastases before RT. Fifteen underwent surgery before RT. Radioactive iodine (RAI) and chemotherapy were used in 70% and 40%, respectively. Median total RT dose was 63 Gy. RESULTS: With two local failures, 2-year local progression-free rate was 85%. There were six deaths, with a 2-year overall survival rate of 60%. For patients with M0 disease, the 2-year distant metastases-free rate was 46%. The worst acute mucositis and pharyngitis was Grade 3 (n = 7 and 3, respectively). Two patients had Grade 3 acute skin toxicity and 2 had Grade 3 acute laryngeal toxicity. No significant radiation-related late effects were reported. CONCLUSIONS: IMRT for TC is feasible and effective in appropriately selected cases. Acute toxicity is manageable with proactive clinical care. Ideal planning target volume doses have yet to be determined. Additional patients and long-term follow-up are needed to confirm these preliminary findings and to clarify late toxicities
— id: 68903, year: 2005, vol: 63, page: 1419, stat: Journal Article,

Plaque radiotherapy for choroidal and ciliochoroidal melanomas with limited nodular extrascleral extension
Augsburger, James J; Schneider, Susan; Narayana, Ashwatha; Breneman, John C; Aron, Bernard S; Barrett, William L; Trichopoulos, Nikolaos
2004 Jun;39(4):380-387, Canadian journal of ophthalmology
BACKGROUND: Currently available clinical information regarding management of posterior uveal melanomas complicated by nodular extrascleral extension is inadequate to determine the role, if any, for plaque radiotherapy in such patients. METHODS: The authors performed a retrospective descriptive study of eight patients with a choroidal or ciliochoroidal melanoma complicated by nodular extrascleral extension who were treated by surgical excision of the extrascleral nodule followed immediately by plaque radiotherapy of the intraocular tumour.The calculated volume of the extrascleral nodule was greater than 1 mm3 but less than 1000 mm3 in all cases, and the intraocular tumour was deemed treatable by plaque radiotherapy in all patients. RESULTS: Four of the eight patients died during available follow-up, three from metastatic melanoma and one from a second cancer.The median length of follow-up for the four surviving patients was 10.1 years.The actuarial 5-year and 10-year all-cause death rates were 37.5% and 53.1% respectively. One of the eight patients experienced local intraocular tumour relapse following plaque therapy and underwent secondary enucleation. None of the patients experienced orbital tumour recurrence or underwent secondary orbital exenteration. INTERPRETATION: Our results coupled with previously published results from another centre suggest that plaque radiotherapy may be an effective local treatment for selected patients with choroidal or ciliochoroidal melanoma complicated by nodular extrascleral extension.The fact that none of the patients in this series or in the previously reported series experienced orbital recurrence following plaque radiotherapy or required secondary orbital exenteration suggests that plaque therapy may be better than enucleation alone in terms of these end points. These results should not be extrapolated, of course, to patients with massive extrascleral tumour extension or a choroidal or ciliochoroidal melanoma too large for plaque radiotherapy
— id: 68906, year: 2004, vol: 39, page: 380, stat: Journal Article,