June 05 2025
Recent results from the NRG-NSABP B-51/RTOG 1304 clinical study showed that the addition of regional nodal irradiation (RNI) does not decrease the rates of invasive breast cancer recurrence in patients whose positive axillary nodes at presentation convert to negative following neoadjuvant chemotherapy. These results were recently published in the New England Journal of Medicine.
The study enrolled 1,641 patients stratified by type of surgery (mastectomy, lumpectomy), hormone receptor status (ER-positive and/or PgR-positive; ER- and PgR-negative), HER2 status, adjuvant chemotherapy use, and pathologic complete response (pCR) in the breast, then randomized to RNI vs. No RNI. Anti-HER2 therapy was required for patients with HER2+tumors, as was endocrine therapy, for patients with hormone-sensitive tumors. The primary endpoint was invasive breast cancer recurrence-free interval (IBCRFI). Final analysis was planned after 172 events or 10 years post-study initiation. At the time-driven analysis, 109 IBCRFI events (63% of the planned 172) were confirmed. RNI did not significantly improve IBCRFI (HR=0.88, 95%CI 0.60-1.28; p=0.51, five-year point estimates: No RNI:91.8%, RNI:92.7%) and did not improve secondary endpoints of loco-regional recurrence-free interval, distant recurrence-free interval, disease-free survival, or overall survival.
“Although numerous prior clinical trials have demonstrated benefit from RNI in patients with positive axillary lymph nodes who undergo surgery first, this trial evaluated RNI in patients who presented with node-positive breast cancer but whose axillary lymph nodes converted to pathologically negative after neoadjuvant chemotherapy. Our study results demonstrate that pCR in axillary lymph nodes predicts for no benefit from RNI. We will continue follow-up for evaluation of longer-term outcomes for these patients,” stated Eleftherios Mamounas, MD, of AdventHealth Cancer Institute, and the lead author of the NRG-NSABP B-51/RTOG 1304 manuscript.
This study was funded by U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), UG1CA189867 (NCORP), and U24CA180803 (IROC) from the National Cancer Institute (NCI), part of the National Institutes of Health; P30CA015083 (R.W. Mutter); Cancer Center Support Grant P30 CA008748 (A.J. Khan); and a Senior Scholar grant from the Susan G. Komen Foundation (R. Jagsi).
Citation
Mamounas EP, Bandos H, White JR, Julian TB, Khan AJ, Shaitelman SF, Torres MA, Vicini FA, Ganz PA, McCloskey SA, Lucas PC, Gupta N, Li XA, McCormick B, Smith BD, Tendulkar RD, Kavadi VS, Matsumoto K, Seaward SA, Irvin WJ Jr., Lin JY, Mutter RW, Muanza TM, Stromberg J, Jagsi R, Weiss A, Curran WJ Jr., Wolmark N. Omitting Regional Nodal Irradiation in Responders to Neoadjuvant Chemotherapy; Published June 4, 2025; N Engl J Med 2025;392:2113-2124; DOI:10.1056/NEJMoa2414859 VOL. 392 NO. 21
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 sex-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