Omitting regional nodal irradiation after response to neoadjuvant chemotherapy Journal Article
| Authors: | Mamounas, E. P.; Bandos, H.; White, J. R.; Julian, T. B.; Khan, A. J.; Shaitelman, S. F.; Torres, M. A.; Vicini, F. A.; Ganz, P. A.; McCloskey, S. A.; Lucas, P. C.; Gupta, N.; Li, X. A.; McCormick, B.; Smith, B.; Tendulkar, R. D.; Kavadi, V. S.; Matsumoto, K.; Seaward, S. A.; Irvin, W. J. Jr; Lin, J. Y.; Mutter, R. W.; Muanza, T. M.; Stromberg, J.; Jagsi, R.; Weiss, A. C.; Curran, W. J. Jr; Wolmark, N. |
| Article Title: | Omitting regional nodal irradiation after response to neoadjuvant chemotherapy |
| Abstract: | 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 one to three 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.). Copyright © 2025 Massachusetts Medical Society. |
| Keywords: | adult; controlled study; human tissue; aged; disease-free survival; middle aged; major clinical study; overall survival; clinical trial; mortality; disease free survival; chemotherapy, adjuvant; neoadjuvant therapy; cancer staging; follow up; lymph node metastasis; antineoplastic agent; lymph nodes; lymphatic metastasis; neoplasm staging; computer assisted tomography; neoplasm recurrence, local; breast cancer; mastectomy; randomized controlled trial; antineoplastic combined chemotherapy protocols; radiotherapy; pathology; breast neoplasms; publication; distant metastasis; radiation response; axillary lymph node; financial management; multicenter study; tumor recurrence; adjuvant chemotherapy; breast tumor; lymph node; irradiation; phase 3 clinical trial; kaplan meier method; neoadjuvant chemotherapy; axilla; drug therapy; anthracycline; therapy; lymph node irradiation; prevention and control; lumpectomy; recurrence free survival; pathological complete response; adverse event; kaplan-meier estimate; lymphatic irradiation; human epidermal growth factor receptor 2 positive breast cancer; humans; human; female; article; breast cancer recurrence |
| Journal Title: | New England Journal of Medicine |
| Volume: | 392 |
| Issue: | 21 |
| ISSN: | 0028-4793 |
| Publisher: | Massachusetts Medical Society |
| Date Published: | 2025-06-05 |
| Start Page: | 2113 |
| End Page: | 2124 |
| Language: | English |
| DOI: | 10.1056/NEJMoa2414859 |
| PUBMED: | 40466065 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed -- Source: Scopus |
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