NRG Oncology’s Practice Changing Study on HA-WBRT plus Memantine Was Among Journal of Clinical Oncology’s Top 5 Downloads in 2020

February 18, 2021

A practice-changing study that showed that Hippocampal Avoidance (HA), the effort of avoiding memory-specific hippocampal neural stem cells, while using intensity-modulated radiotherapy during whole-brain radiotherapy (WBRT) plus memantine, a cognition-enhancing medication, for brain metastases better preserves cognitive function and patient-reported symptoms with no difference in survival -- was one of the top 5 articles published in the Journal of Clinical Oncology in 2020 based on downloads and social media activity.

The study - Hippocampal Avoidance during Whole-Brain Radiotherapy plus Memantine for Patients with Brain Metastases: Phase III Trial NRG Oncology CC001 – demonstrated that HA-WBRT plus memantine should be considered standard of care, compared to WBRT plus the drug memantine, for patients with brain metastases and good performance status who plan to receive WBRT with no metastases in the HA region.

“To our knowledge, this trial provides the first definitive clinical evidence that the hippocampal neuro-regenerative niche is important to the pathophysiology of radiotherapy-induced cognitive decline and builds on extensive preclinical work and prior clinical studies,” said the multi-center study’s co-lead author Paul D. Brown, MD, radiation oncologist in the Department of Radiation Oncology at the Mayo Clinic in Rochester, Minnesota. Dr. Vinai Gondi, co-lead author, radiation oncologist at Northwestern Medicine Cancer Center Warrenville, noted, “with these findings, HA-WBRT plus memantine should be considered a standard of care for patients planning to receive WBRT.”

Between July 2015 and March 2018, 518 patients with brain metastases were randomly assigned after entry into the study. Median follow-up for alive patients was 7.9 months. Risk of cognitive failure was significantly lower after HA-WBRT plus memantine versus WBRT plus memantine (adjusted hazard ratio, 0.74; 95% CI, 0.58 to 0.95; P = .02). This difference was attributable to less deterioration in executive function at 4 months (23.3% v 40.4%; P = .01) and learning and memory at 6 months (11.5% v 24.7% [P = .049] and 16.4% v 33.3% [P = .02], respectively). Treatment arms did not differ significantly in overall survival (OS), intracranial progression-free survival (PFS), or toxicity. At 6 months, using all data, patients who received HA-WBRT plus memantine reported less fatigue (P = .04), less difficulty with remembering things (P = .01), and less difficulty with speaking (P = .049) and using imputed data, less interference of neurologic symptoms in daily activities (P = .008) and fewer cognitive symptoms (P = .01).

NRG Oncology CC001 was supported by grants UG1CA189867 (NRG Oncology NCORP) and U24CA180803 (IROC) from the National Cancer Institute (NCI).

Brown PD, Gondi V, Pugh S, Tome WA, Wefel JS, Armstrong TS, Bovi JA, Robinson C, Konski A, Khuntia D, Grosshans D, Benzinger TLS, Bruner D, Gilbert MR, Roberge D, Kundapur V, Devisetty K, Shah S, Usuki K, Anderson BM, Stea B, Yoon H, Li J, Laack NN, Kruser TJ, Chmura SJ, Shi W, Deshmukh S, Mehta MP, Kachnic LA; for NRG Oncology. Hippocampal Avoidance During Whole-Brain Radiotherapy Plus Memantine for Patients With Brain Metastases: Phase III Trial NRG Oncology CC001. J Clin Oncol. 2020 Apr 1;38(10):1019-1029. doi: 10.1200/JCO.19.02767. Epub 2020 Feb 14. PubMed PMID: 32058845; PubMed Central PMCID: PMC7106984.

About NRG Oncology
NRG Oncology conducts practice-changing, multi-institutional clinical and translational research to improve the lives of patients with cancer. Founded in 2012, NRG Oncology is a Pennsylvania-based nonprofit corporation that integrates the research of the legacy National Surgical Adjuvant Breast and Bowel Project (NSABP), Radiation Therapy Oncology Group (RTOG), and Gynecologic Oncology Group (GOG) programs. The research network seeks to carry out clinical trials with emphases on gender-specific malignancies, including gynecologic, breast, and prostate cancers, and on localized or locally advanced cancers of all types. NRG Oncology’s extensive research organization comprises multidisciplinary investigators, including medical oncologists, radiation oncologists, surgeons, physicists, pathologists, and statisticians, and encompasses more than 1,300 research sites located world-wide with predominance in the United States and Canada. NRG Oncology is supported primarily through grants from the National Cancer Institute (NCI) and is one of five research groups in the NCI’s National Clinical Trials Network.



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