Omitting Regional Nodal Irradiation after Response to Neoadjuvant Chemotherapy

Author(s): Eleftherios P. Mamounas, M.D.¹; Hanna Bandos, Ph.D.^2,3; Julia R. White, M.D.⁴; Thomas B. Julian, M.D.⁵; Atif J. Khan, M.D.⁶; Simona F. Shaitelman, M.D.⁷; Mylin A. Torres, M.D.⁸; Frank A. Vicini, M.D.⁹; Patricia A. Ganz, M.D.^10,11; Susan A. McCloskey, M.D.¹²; Peter C. Lucas, M.D., Ph.D.^13,14,15,16; Nilendu Gupta, Ph.D.¹⁷; X. Allen Li, Ph.D.¹⁸; Beryl McCormick, M.D.⁶; Benjamin Smith, M.D.⁷; Rahul D. Tendulkar, M.D.^19,20; Vivek S. Kavadi, M.D.²¹; Koji Matsumoto, M.D.²²; Samantha Andrews Seaward, M.D.²³; William J. Irvin, Jr., M.D.²⁴; Jolinta Y. Lin, M.D.⁸; Robert W. Mutter, M.D.²⁵; Thierry M. Muanza, M.Sc.²⁶; Jannifer Stromberg, M.D.²⁷; Reshma Jagsi, M.D., Ph.D.⁸; Anna C. Weiss, M.D.²⁸; Walter J. Curran, Jr., M.D.²⁹; Norman Wolmark, M.D.^14,15,30;

Source: N Engl J Med 2025;392:2113-2124

Dr. Maen Hussein's Thoughts

No need for radiation if neoadjuvant therapy led to a complete response in the lymph nodes.

BACKGROUND

The benefit of regional nodal irradiation in the treatment of breast cancer is well established for patients with pathologically positive axillary nodes, but whether it is also beneficial for patients whose nodes become pathologically tumor free (ypN0) after neoadjuvant chemotherapy remains unclear.

METHODS

We evaluated whether regional nodal irradiation improves outcomes in patients with biopsy-proven, node-positive breast cancer who reach ypN0 status after neoadjuvant chemotherapy. Patients with breast cancer with a clinical stage of T1 to T3 (tumor size, ≤2 cm to >5 cm), N1, and M0 (indicating spread to movable, ipsilateral level I and II axillary lymph nodes but no distant metastasis) who had ypN0 status after neoadjuvant chemotherapy were randomly assigned to receive regional nodal irradiation or no regional nodal irradiation. The primary end point was the interval of freedom from invasive breast cancer recurrence or death from breast cancer (invasive breast cancer recurrence—free interval). Secondary end points included the locoregional recurrence—free interval, the distant recurrence—free interval, disease-free survival, and overall survival. Safety was also assessed.

RESULTS

A total of 1641 patients were enrolled in the trial; 1556 were included in the primary-event analysis: 772 in the irradiation group and 784 in the no-irradiation group. After a median follow-up of 59.5 months, 109 primary end-point events (50 in the irradiation group and 59 in the no-irradiation group) had occurred. Regional nodal irradiation did not significantly increase the invasive breast cancer recurrence—free interval (hazard ratio, 0.88; 95% confidence interval, 0.60 to 1.28; P=0.51). Point estimates of survival free from the primary end-point events were 92.7% in the irradiation group and 91.8% in the no-irradiation group. Regional nodal irradiation did not increase the locoregional recurrence—free interval, the distant recurrence—free interval, disease-free survival, or overall survival. No deaths related to the protocol-specified therapy were reported, and no unexpected adverse events were observed. Grade 4 adverse events occurred in 0.5% of patients in the irradiation group and 0.1% of those in the no-irradiation group.

CONCLUSIONS

The addition of adjuvant regional nodal irradiation did not decrease the risk of invasive breast cancer recurrence or death from breast cancer in patients who had negative axillary nodes after neoadjuvant chemotherapy. (Funded by the National Institutes of Health; NSABP B-51—Radiation Therapy Oncology Group 1304 ClinicalTrials.gov number, NCT01872975.)

Author Affiliations

¹AdventHealth Cancer Institute, Orlando, FL; ²NRG Oncology Statistical and Data Management Center, Pittsburgh; ³University of Pittsburgh School of Public Health, Department of Biostatistics and Health Data Science, Pittsburgh; ⁴University of Kansas Medical Center Comprehensive Cancer Center, Kansas City; ⁵Allegheny Health Network Cancer Institute, Pittsburgh; ⁶Memorial Sloan Kettering Cancer Center, New York; ⁷University of Texas M.D. Anderson Cancer Center, Houston; ⁸Winship Cancer Institute, Emory University School of Medicine, Atlanta; ⁹Michigan Healthcare Professionals, Pontiac; ¹⁰Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles; ¹¹UCLA Fielding School of Public Health, Los Angeles; ¹²University of California, Los Angeles, Los Angeles; ¹³National Surgical Adjuvant Breast and Bowel Project Pathology Lab, Pittsburgh; ¹⁴University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh; ¹⁵University of Pittsburgh School of Medicine, Pittsburgh; ¹⁶Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN; ¹⁷Ohio State University, James Cancer Hospital, Columbus; ¹⁸Medical College of Wisconsin, Milwaukee; ¹⁹Case Western Reserve University Case Comprehensive Cancer Center, Cleveland; ²⁰Taussig Cancer Center, Cleveland Clinic, Cleveland; ²¹Texas Oncology, US Oncology Network, The Woodlands; ²²Hyogo Cancer Center, Akashi, Hyogo, Japan; ²³Kaiser Permanente National Cancer Institute Community Oncology Research Program, Vallejo, CA; ²⁴Bon Secours Cancer Institute, Southeast Clinical Oncology Research Consortium, National Cancer Institute Community Oncology Research Program, Midlothian, VA; ²⁵Mayo Clinic, Rochester, MN; ²⁶McGill University, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montreal; ²⁷Corewell Health, Oakland University Beaumont School of Medicine, Sterling Heights, MI; ²⁸University of Rochester School of Medicine and Dentistry, Rochester, NY; ²⁹Piedmont Oncology Institute, Atlanta; ³⁰National Surgical Adjuvant Breast and Bowel Project Foundation, Pittsburgh;

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