PHILADELPHIA, PA - Results from the NRG Oncology clinical study NRG-CC001 concluded that lowering radiotherapy dose to hippocampal stem cells improves cognitive and patient-reported outcomes for patients with brain metastases. These findings were presented at Plenary Sessions at the 2018 Society for Neuro-Oncology (SNO) and the 2019 American Academy of Neurology (AAN) Annual Meetings and are now published in the Journal of Clinical Oncology.
"NRG-CC001 provides physicians with the information needed to offer patients a safer alternative to standard whole-brain radiotherapy. Hippocampal avoidance whole-brain radiotherapy with memantine should be a standard of care that providers offer for patients with brain metastases who are seeking whole-brain radiotherapy," stated Paul D. Brown, MD, of Mayo Clinic and co-lead author of the NRG-CC001 manuscript.
The NRG-C001 phase III trial enrolled 518 patients, which were randomly assigned to either receive whole-brain radiotherapy plus memantine with hippocampal avoidance or standard whole-brain radiotherapy plus memantine. The primary endpoint of the trial was cognitive function failure and the trial looked at secondary endpoints including overall survival, intracranial progression-free survival, toxicity, and patient-reported neurologic symptoms.
"Hippocampal avoidance during whole-brain radiotherapy in NRG-CC001 leads to a 26% relative reduction in cognitive toxicity risk following treatment. This is the first definitive and most important clinical evidence that the hippocampus is important in determining the negative effects that radiotherapy can have on cognitive function," added Vinai Gondi, MD, the Director of Research at the Northwestern Medicine Chicago Proton Center, Co-Director of the Brain Tumor Center at the Northwestern Medicine Cancer Center Warrenville, and co-lead author of the NRG-CC001 manuscript.
With a median follow up of 7.9 months, the risk of cognitive function failure was lower following hippocampal avoidance whole-brain radiotherapy versus standard whole-brain radiotherapy (adjusted hazard ratio, 0.74, 95% confidence interval: 0.58-0.95, p=0.02). The difference was attributable to less deterioration in executive function at 4 months (23.3% vs. 40.4%, p=0.01) and learning and memory at 6 months (11.5% vs. 24.7%, p=0.049, and 16.4% vs. 33.3%, p=0.02, respectively). At 6 months, patients who received whole-brain radiotherapy with hippocampal avoidance reported less fatigue (p=0.04), less difficulty remembering things (p=0.01), and less difficulty speaking (p=0.0049), in addition to fewer cognitive symptoms (p=0.01) and less interference of neurologic symptoms in daily activities (p=0.008). There was no statistically significant difference between overall survival, intracranial progression-free survival, or toxicity between treatment arms.
NRG-CC001 was supported by grants UG1CA189867 (NRG Oncology NCORP) and U24CA180803 (IROC) from the National Cancer Institute (NCI). Clinicaltrials.gov identifier: NCT02360215.
Brown PD, Gondi V, Pugh SL, 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. Hippocampal Avoidance during Whole-Brain Radiotherapy plus Memantine for Patients with Brain Metastases: Phase III Trial NRG Oncology CC001. J Clin Oncol. Feb. 14, 2020. doi: 10.1200/JCO.19.02767. [Epub ahead of print] PubMed PMID: 32058845
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.