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2002 Background: This study sought to update the predictive significance of the three WHO-defined molecular glioma subgroups ( IDHwt, IDHmt/noncodel, and IDHmt/codel) in the subset of specimens available for analysis in NRG Oncology/RTOG 9802, a phase III trial of high-risk low-grade gliomas (LGGs) treated with radiation (RT) with and without PCV after biopsy/surgical resection. Notably, this is the first phase III study to evaluate the predictive value of the WHO subgroups in LGGs using prospectively-collected, well-annotated long-term overall survival data, in a post-hoc analysis. Methods: IDH1/2 mutation status was determined by immunohistochemistry and/or next-generation sequencing. 1p/19q status was determined by Oncoscan and/or 450K methylation data. Treatment effects on overall survival (OS) and progression-free survival (PFS) by marker status were determined by the Cox proportional hazard model and tested using the log-rank test in a secondary and exploratory analysis. Results: Of all the randomized eligible high-risk G2 patients (N = 251) in NRG Oncology/RTOG 9802, 106(42%) patients had tissue available with sufficient quality DNA for profiling. Of these, 80(75%) were IDHmut; 43(41%) were IDHmut/non-co-deleted, 37(35%) were IDHmut/co-deleted, and 26(24%) were IDHwt. Upon univariate analyses, no significant difference in either PFS or OS was observed with the addition of PCV in the IDHwt subgroup. Both the IDHmut/non-co-deleted and IDHmut/co-deleted subgroups were significantly correlated with longer PFS (HR = 0.32; p = 0.003; HR = 0.13; p < 0.001) and OS (HR = 0.38; p = 0.013; HR = 0.21; p = 0.029) in the RT plus PCV arm, respectively. Conclusions: Our analyses suggest that both IDHmut/non-co-deleted and IDHmut/co-deleted subgroups received benefit from treatment with PCV although sample size is limited and analyses are post-hoc. Our results also support the notion that IDHwt high-risk LGG patients do not benefit from the addition of PCV to RT. Funding: U10CA180868, U10CA180822, and U24CA196067. Also, R01CA108633, R01CA169368, RC2CA148190, U10CA180850-01, BTFC, OSU-CCC (all to AC). Clinical trial information: NCT00003375.

e14091Background: Allele-specific copy number analysis of tumors (ASCAT) is a quantitative method of assessing copy number variations that accounts for non-aberrant cell contributions and tumor plo...

2031 Background: Grade II glioma patients with subtotal resection (STR) or age ≥ 40 are considered high risk. RTOG 9802 demonstrated that for these high-risk patients, chemotherapy and radiation therapy improved overall survival (OS) compared to radiation alone. The purpose of this study is to compare the OS of high risk, grade II glioma patients treated with adjuvant chemotherapy alone (CA) to chemotherapy and radiation therapy (CRT). Methods: Using the National Cancer Data Base (NCDB), high risk (age ≥ 40 or STR) grade II glioma patients with oligodendroglioma, astrocytoma, or mixed tumors were identified. Patients receiving CA were compared to patients receiving CRT. Univariate and multivariable analyses (MVA) were performed. Propensity score (PS) matching was utilized to account for difference in patient characteristics. Kaplan Meier statistics were utilized to compare OS. Results: 1054 high risk, grade II glioma patients were identified, 47.1% receiving CA and 52.9% receiving CRT. Median follow up time was 55.1 months. Patients treated with CA were statistically more likely (all p < 0.05) to be oligodendroglioma histology (65.5% vs. 34.2%), 1p/19 co-deleted (22.8% vs. 7.5%), younger median age (47 vs. 48 years) and treated at an academic program (65.2% vs. 50.3%). MVA demonstrated treatment type was not a significant predictor for OS (p = 0.125), while tumor size > 6cm, astrocytoma histology, and older age were predictors for worse survival (all p < 0.05). Utilizing 1:1 PS matching, with 662 total patients, OS was statistically similar (p = 0.919) for CA and CRT at 5 years (69.1% vs. 68.5%, respectively) and 7 years (55.5% vs. 60.0%, respectively). Conclusions: In this retrospective analysis of the NCDB, long term OS for high-risk, grade II glioma patients treated with CA appears similar to CRT. These findings are hypothesis generating, with the standard of care still remaining CRT as established by RTOG 9802. Prospective clinical trials comparing CA and CRT are warranted.

2004 Background: RTOG 0825 evaluated overall survival (OS) and progression-free survival (PFS) differences in patients with newly diagnosed GBM treated with standard chemoradiation, maintenance temozolomide and placebo (Arm 1) or bevacizumab (Arm 2). While OS was equivalent, PFS was longer in Arm 2. Longitudinal NCF testing was performed to evaluate clinical benefit. Methods: NCF was evaluatedat baseline and while on study and progression free with the Hopkins Verbal Learning Test-Revised (HVLT-R), Trail Making Test (TMT) and Controlled Oral Word Association (COWA). Change in NCF from baseline was categorized using the reliable change index. Differences between treatment arms were compared at follow-up evaluations. Additionally, baseline (B) and early changes (EC) (B to week 10) in NCF were examined as prognostic factors. Results: 542 patients consented and 507 randomized patients participated, with test completion rates at weeks 0 (B), 10, 22, and 34 of 94-97, 69-73, 59-64, and 53-58%, respectively. Mean test performance at B was equivalent between arms and ranged from -0.8 to -4.8 SDs below healthy population norms with global NCF on a composite variable at -2.0 SDs. There were no statistically significant between arm differences in frequency of improvement through week 34. Decline on COWA (verbal measure of executive function) at week 34 relative to baseline was more common (16.1 vs 5.7%) in patients in Arm 1 (p

2003 Background: RTOG 0825 tested if adding bevicizumab (BEV) to standard chemoradiation improves survival (OS) or progression free survival (PFS) in newly diagnosed GBM. While OS was equivalent, PFS was longer with Bev (Arm 2) than with placebo (Arm 1). Patients completed quality of life and symptom PROs to evaluate clinical benefit. Methods: The M.D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) and the EORTC core Quality of life Questionnaire and brain tumor module (EORTC QLQ-C30/BN20), were completed by pts at baseline (B) and longitudinally (wk 6, 10, 22, 34, and 46) while on study. The difference between treatment arms were compared from B with evaluation in subsequent weeks in those pts without disease progression; and early change (EC) (baseline to wk 10) between those with and without progression as predictors for OS and PFS. Results: 542pts consented to participate on this trial, and 507 randomized pts participated, with completion of forms by 94% at baseline, 75% at wk 10, 61% at wk 22, and 58% at wk 34. There was a trend for all MDASI-BT symptom groupings to be worse in Arm 2, with significant findings in treatment symptoms at wk 22 and wk 34; both affective and generalized disease symptoms were also significantly worse. For EORTCQLQ30/BN20, differential effects varied at each time point, with no persistent differences. For the MDASI-BT, B neurologic symptom grouping and EC in cognitive symptoms were prognostic for both OS and PFS. For the EORTC QLQ30/BN20, global QOL and motor dysfunction at B as well as EC in communication and leg weakness were prognostic for OS; whereas physical function at B and EC in headaches, seizures, and weak legs were prognostic for PFS. Conclusions: The longitudinal collection of PROs in this phase III trial revealed important treatment-related differences as there was overall more deterioration in symptoms and QOL in Arm 2 as compared to Arm 1, with persistent significant differences in treatment associated symptoms. B and EC tumor associated symptoms on both PRO tools were prognostic for OS and PFS. Longitudinal modeling is ongoing to further assess for differential impact of treatment on symptoms and QOL. Support: U10 CA21661, U10 CA37422 and Genentech, Inc. Clinical trial information: NCT00884741.

118 Background: To determine the influence of radiotherapy (XRT) technique on local control in breast cancer (BRCA) patients, we evaluated the relationship between PET/CT-identified locoregional recurrences (LRR) and prior definitive XRT treatment plans. Methods: Twenty-two consecutive LRRs of BRCA were identified by PET/CT in 19 patients treated from 2004-2011 with definitive post-operative radiation for their BRCA. PET/CT and original XRT CT simulation images were fused using a B-spline deformable registration algorithm (VelocityAI, Velocity Medical Solutions, Atlanta, GA) to correct for posture and soft tissue changes. Prior XRT dose to the FDG avid LRR region was calculated. LRR was classified as in-field, marginal or out-of-field. In-field LRRs were defined as ≥95% of the LRR volume receiving ≥95% of the prescribed dose (45–50.4 Gy). Marginal misses were LRRs at the field edge and/or not receiving ≥95% of the prescribed dose. Out-of-field LRRs were LRRs intentionally not treated with the original XRT plan. Results: Four LRRs were in-field, 8 were marginal and 10 were out-of-field, with two patients having both in-field and out-of-field LRRs and one having a marginal and out-of-field LRRs. Three in-field, 3 marginal and 6 out-of-field LRRs occurred simultaneously with distant metastasis (DM). In-field LRRs received a median dose of 48.4Gy (range 45-50Gy). Two in-field LRRs were marginal misses of the additional 15 Gy boost dose (median dose received 53.5 Gy); both patients had high grade, ER/PR-, and HER2 + tumors. In the 7 patients with triple negative tumors, there were 4 marginal, 4 out-of-field, and no in-field LRRs. Among marginal LRRs, a median dose of 33Gy (range 2–45.6Gy) was delivered. Out-of-field LRRs occurred in 5 supraclavicular and 5 internal mammary lymph nodes. With a median follow-up period of 3.7 yrs, the 5-yr disease-free survival (DFS) in patients with an isolated LRR is 55.6%, while in those recurring with DM, the DFS is 22.5%. Conclusions: Our study is one of the first to systematically evaluate the influence of XRT technique over local control in BRCA. Due to the number of marginal and out-of-field LRRs, our data suggest that XRT field design and dose are important factors in preventing LRRs in addition to tumor biology.

8590 Background: A previously described diagnosis-specific graded prognostic assessment (DS-GPA) for melanoma showed that number of brain metastases (BM) and Karnofksy Performance Score (KPS) were ...

e19023 Background: The brain is a frequent site of melanoma metastases (mets) and is associated with a poor prognosis. Therapeutic options are limited and include surgical resection, whole brain ra...

1538 Background: Significant tumor control and prolongation of survival have been demonstrated by combined use of radiosurgery and antivascular agent, Arsenic Trioxide (ATO), in rodent gliosarcoma model in rats. This agent is now undergoing clinical evaluation in the NABTT Brain Tumor Consortium in a Phase I trial with ATO dose escalation in combination with fractionated radiation therapy. Since this agent showed rapid effect on the tumor vasculature in the animal studies, MRI perfusion and diffusion studies were performed shortly following ATO administration. Methods: The patients were treated with external beam radiotherapy 60 Gy in 6 weeks with ATO at a starting dose of 0.25 mg/kg once a week during the course radiotherapy. ATO dose was escalated by 0.05 mg. The perfusion images were acquired using a Echo Planar Image (EPI) sequence. Perfusion parameters were Mean Transit Time (MTT), relative Cerebral Blood Volume (rCBV), and relative Cerebral Blood Flow (rCBF). The perfusion parameter values under reg...