Laack, Nadia N.

Abstract BACKGROUND NRG-CC001 sought to evaluate the neuro-protective effects of avoiding the peri-hippocampal stem cell niche using intensity-modulated radiotherapy during WBRT. METHODS Patients with brain metastasis were stratified by RPA class and prior radiosurgery/surgery and randomized to WBRT+M or HA-WBRT+ Memantine (M) (30Gy in 10 fractions). Standardized NCF tests and the M.D. Anderson Symptom Inventory Brain Tumor (MDASI-BT) were obtained at baseline, 2, 4, 6, and 12 months (mos). The primary endpoint was NCF failure defined using the reliable change index. Pre-specified secondary endpoints included patient-reported symptoms using the MDASI-BT. Time to NCF was reported as cumulative incidence (with death without NCF failure as a competing risk); between-arms differences were tested using Gray’s test. Deterioration at discrete time-points were tested using chi-square tests. MDASI-BT symptom burden, interference, and cognitive and neurologic burden were analyzed using mixed effects models and t-tests within the model using Hochberg’s multiplicity adjustment. RESULTS A total of 518 patients were randomized from 7/2016 to 3/2018. Median follow-up for alive patients was 12.1 mos, with no difference between arms in terms of toxicity, overall survival or intracranial progression-free survival. HA-WBRT+M was associated with lower risk of NCF failure (adjusted HR=0.739, 95% CI: 0.577–0.945, p=0.0.016), with differences first noted at 4 mos in Trail Making Test Part-B (23.3% vs. 40.4% deteriorated, p=0.012). Age did not dilute treatment effect. HA-WBRT+M was associated with reduced cognitive symptom burden in an imputed model (estimate=-0.29, p=0.0425), and also reduced overall symptom burden (p< 0.0001) and interference (p< 0.0016) at 6 mos. CONCLUSIONS The addition of HA to WBRT+M preserved NCF and reduced patient reported cognitive symptom burden, overall symptom burden and symptom interference and should be considered standard of care for any patient fit enough to have WBRT. Supported by grants UG1CA189867 (NCORP), U10CA180868 (NRG Oncology Operations), DCP from the National Cancer Institute.

Objective: The Pediatric Proton/Photon Consortium Registry (PPCR) is a comprehensive data registry composed of pediatric patients treated with radiation. It was established to expedite outcomes-based research. The attributes which allow the PPCR to be a successful collaboration are reviewed. Methods and materials: Current eligibility criteria are radiotherapy patients &lt; 22 years treated at one of the 15 US participating institutions. Detailed health and treatment data are collected about the disease presentation and treatment exposures, and annually thereafter, in REDCap (Research Electronic Data Capture). DICOM (Digital Imaging and Communications in Medicine) imaging and radiation plans are collected through MIM/MIMcloud. An optional patient-reported quality-of-life (PedsQL) study is administered at 10 sites. Results: Accrual started October 2012 with 2,775 participants enrolled as of 25 July 2019. Most patients, 62.0%, were treated for central nervous system (CNS) tumors, the most common of which are medulloblastoma (n = 349), ependymoma (n = 309), and glial/astrocytoma tumors (n = 279). The most common non-CNS diagnoses are rhabdomyosarcoma (n = 284), Ewing’s sarcoma (n = 153), and neuroblastoma (n = 130). While the majority of participants are US residents, 18.7% come from 36 other countries. Over 685 patients participate in the PedsQL study. Conclusions: The PPCR is a valuable research platform capable of answering countless research questions that will ultimately improve patient care. Centers outside of the USA are invited to participate directly or may engage with the PPCR to align data collection strategies to facilitate large-scale international research. Advances in knowledge: For investigators looking to carry out research in a large pediatric oncology cohort or interested in registry work, this paper provides an updated overview of the PPCR.

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.