Influence of BRAF and NRAS Mutations on Distant Intracranial ...

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S. Rajakesari,2 N.D. Arvold,2 S. Floyd,3 K.S. Oh,4 J.S. Loeffler,4 and H.A. ... Beth Israel Deaconess Medical Center, Boston, MA, 4Department of. Radiation ...

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Volume 87  Number 2S  Supplement 2013 lesion and time to onset of the brain metastases are reliable and should be considered at the time of the patient evaluation. Author Disclosure: H. Faria Braga: None. I.T. Carvalho: None. A.T.T. Chen: None. R.C. Villar: None. E.C. Souza: None. M.J. Teixeira: None. W. Nadalin: None. E. Weltman: None.

2186 Influence of BRAF and NRAS Mutations on Distant Intracranial Recurrence and Survival in Metastatic Melanoma Following Radiosurgery C.E. Rutter,1 E. Giesen,2 J.B. Yu,1 R.S. Bindra,1 H.M. Kluger,1 and V.L. Chiang1; 1Yale New Haven Hospital, New Haven, CT, 2Yale School of Medicine, New Haven, CT Purpose/Objective(s): The clinical course of patients with metastatic melanoma with brain metastases can be quite varied. This study aims to compare outcomes based on mutational status of BRAF and NRAS following stereotactic radiosurgery (SRS). Materials/Methods: A prospectively maintained database of patients receiving SRS between November 2002 and December 2012 was queried to determine the rate of new brain metastasis development in patients with metastatic melanoma following SRS. Patients receiving whole brain radiation therapy as first line treatment were excluded. BRAF and NRAS mutational status was determined by Sanger sequencing. The impact of mutation status on risk of distant intracranial recurrence and overall survival (OS) from brain metastasis diagnosis was determined using Poisson regression with robust estimation of errors and Cox proportional hazards analyses, respectively. Other factors including systemic disease control and intracranial disease burden were explored as potential predictors of recurrence and OS in a similar fashion. Results: One hundred eight patients were identified with a mean age of 63 years (range, 24-90 years), of which 68% were male and 94.4% were white. A NRAS mutation was found in 9 patients (8.3%) and BRAF mutation in 24 (22.2%). Median OS from brain metastasis diagnosis was 312 days (range, 228-471 days). A larger number of brain metastases at diagnosis and uncontrolled systemic disease were found to be univariate predictors of worsened OS (HR 1.04, p Z 0.012; HR 2.52, p Z 0.001, resp). Only uncontrolled systemic disease was a significant predictor of OS on multivariate analysis (HR 10.63, p Z 0.022). Mutation status for BRAF and NRAS did not appear to influence survival in our cohort. NRASmutated patients were found to be at significantly higher risk of distant intracranial recurrence as compared to wild type patients (IRR for wild type compared to NRAS-mutated, 0.27, p Z 0.011). No other variables were found to be significant predictors of recurrence. Conclusions: Although metastatic melanoma follows a highly variable clinical course, NRAS mutations appear to influence the number of intracranial recurrences experienced by patients. Other disease factors including systemic disease control and number of brain metastases at diagnosis seem to influence OS. Author Disclosure: C.E. Rutter: None. E. Giesen: None. J.B. Yu: None. R.S. Bindra: None. H.M. Kluger: None. V.L. Chiang: None.

2187 The Impact of Different Hypofractionated Stereotactic Radiation Therapy Regimens for Brain Metastases on Local Control and Toxicity R.B. Jimenez,1 B.M. Alexander,2 A. Mahadevan,3 A. Niemierko,4 S. Rajakesari,2 N.D. Arvold,2 S. Floyd,3 K.S. Oh,4 J.S. Loeffler,4 and H.A. Shih4; 1Harvard Radiation Oncology Program, Boston, MA, 2 Department of Radiation Oncology, Brigham & Women’s Hospital/DanaFarber Cancer Institute, Boston, MA, 3Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA, 4Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA

Purpose/Objective(s): Hypofractionated stereotactic radiation therapy (hSRT) enables short course, high dose radiation delivery to brain tumors that are less ideal for single fraction treatment due to larger size, irregular shape, or close proximity to sensitive structures. Here, we report the collective hSRT experience of 3 major academic institutions to identify optimal treatment regimens for maximizing local control and minimizing morbidity. Materials/Methods: We performed a retrospective review across 3 academic hospitals of patients treated with hSRT for solid brain metastases using variable dose schedules from 2001-2011. Endpoints included 1) local failure, defined either radiographically as >25% increase in the largest axial diameter of the index lesion on contrast-enhancing T1 MRI without spontaneous regression, or pathologically from surgery at progression, 2) acute toxicity (Common Toxicity Criteria v3.0), and 3) symptomatic radionecrosis. Competing risks methodology was used estimate the actuarial rate of local failure and to assess the association of clinical and demographic covariates with time to local failure. Results: A total of 156 patients were identified; 100 female, 56 male. Median age at treatment was 60 years (range, 21-93 years). Common tumor histologies included breast 30% (47), lung 32% (50), melanoma 22% (35), and renal cell carcinoma 15% (24). The majority of lesions were supratentorial (57%). Most lesions measured less than 2 cm (46%), 36% were between 2-3 cm, and 17% were >3 cm (range, 0.4-6.4 cm). Median target volume was 3.99 cc (range, 0.04-58.42 cc). Median total hSRT dose was 25 Gy (range, 12-36), median fractional dose was 5 Gy (range, 2.5-11 Gy), and median number of fractions was 5 (range, 2-10). The most common dose schedules were 25 Gy in 5 Gy fractions (49%) and 24 Gy in 8 Gy fractions (14%). Cumulative incidence of local failure at 3, 6, 12, 18, and 24 months was 13%, 29%, 44%, 60%, and 64%, respectively. Univariate and multivariable competing risks analysis included total prescription dose, target volume, tumor histology, and tumor location. Total prescription dose was the only factor statistically significantly associated with time to local failure on univariate (p Z 0.02) and multivariable analysis (p Z 0.004, AHR 0.85). Five patients experienced seizures during or within 10 days of hSRT completion and 5 patients developed radionecrosis. All patients with documented radionecrosis received prior radiation to the index lesion in the form of WBRT, SRS, or both. Conclusions: Our collective series of hSRT for brain metastases found total prescription dose to be the only risk factor significantly associated with local failure. Dose per fraction had no association with tumor control. Both acute and long-term toxicity events from hSRT were modest. Author Disclosure: R.B. Jimenez: None. B.M. Alexander: None. A. Mahadevan: F. Honoraria; CyberKnife CME Presenter. A. Niemierko: None. S. Rajakesari: None. N.D. Arvold: None. S. Floyd: None. K.S. Oh: None. J.S. Loeffler: None. H.A. Shih: E. Research Grant; NCI/NIH grant funding. Q. Leadership; Editor for Red Journal, Writer for Up-to-Date.

2188 Proton Radiation Therapy for Pediatric Central Nervous System Ependymoma: Clinical Outcomes for 70 patients R. Sethi,1 B.Y. Yeap,2 R. Marino,2 K.J. Marcus,3 P. Caruso,2 M.B. Pulsifer,2 D. Ebb,2 N.J. Tarbell,2 T.I. Yock,2 and S.M. MacDonald2; 1 Harvard Medical School, Boston, MA, 2Massachusetts General Hospital, Boston, MA, 3Boston Children’s Hospital, Boston, MA Purpose/Objective(s): The best outcomes for localized ependymoma are achieved with maximal surgical resection and radiation to the tumor bed. Minimizing unnecessary exposure to radiation is of paramount importance for these often very young children. Proton radiation spares healthy tissues outside the target region, but reports of clinical outcomes are scarce. We report survival, cognitive and endocrine outcomes for 70 patients with intracranial ependymoma. Materials/Methods: Seventy patients with localized ependymoma treated with involved field proton radiation between October, 2000 and February

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