Armando Orlandi, Medical Director at the Agostino Gemelli University Hospital Foundation IRCCS, shared a post on LinkedIn:
“Practice-changing Results. NEJM Study Challenges Regional Nodal Irradiation in Breast Cancer
A groundbreaking NEJM study (June 2025) by Mamounas et al. is reshaping how we approach radiation therapy in breast cancer patients who achieve pathological complete response after neoadjuvant chemotherapy.
Study Overview: NSABP B-51–RTOG 1304 Trial
1,641 patients with biopsy-proven node-positive breast cancer (T1-T3, N1, M0)
All achieved ypN0 status after neoadjuvant chemotherapy
Randomized to regional nodal irradiation vs. no regional nodal irradiation
Median follow-up: 59.5 months
Key Findings
Primary Endpoint: Invasive breast cancer recurrence-free interval
No significant benefit from regional nodal irradiation (HR 0.88, 95% CI 0.60-1.28, P=0.51)
5-year event-free survival: 92.7% (irradiation) vs 91.8% (no irradiation)
Clinical Practice Implications
What This Means for Daily Practice:
De-escalation Strategy: Patients with initially node-positive disease who achieve ypN0 can safely omit regional nodal irradiation
Quality of Life: Reduced radiation burden = fewer side effects (study showed 5.7% vs 3.3% grade 3 dermatitis)
Resource Optimization: More efficient use of radiation therapy resources without compromising outcomes
Personalized Medicine: Pathological response to neoadjuvant therapy can now guide radiation decisions
Patient Population Most Relevant:
79% had HER2+ or triple-negative breast cancer
78.2% achieved pathological complete response in breast and nodes
Results consistent across surgery types (lumpectomy vs mastectomy)
Important Considerations
Subgroup Analysis: Exploratory findings suggest potential differences in triple-negative (HR 2.30) vs HR+/HER2- disease (HR 0.41) – longer follow-up needed
Lower Event Rate: Actual recurrence rate was 40% lower than projected, reflecting improved modern outcomes
Looking Forward
This study supports a paradigm shift toward:
Response-adapted therapy based on pathological outcome
Reduced treatment burden without compromising cure rates
Enhanced integration of neoadjuvant approach benefits
Bottom Line: For patients achieving ypN0 after neoadjuvant chemotherapy, we can confidently omit regional nodal irradiation, focusing our efforts on patients who truly need this intervention.”
Title: Omitting Regional Nodal Irradiation after Response to Neoadjuvant Chemotherapy
Authors: Eleftherios Mamounas, Hanna Bandos, Julia White, Thomas Julian, Atif Khan, Simona Shaitelman, Mylin Torres, Frank Vicini, Patricia Ganz, Susan McCloskey, Peter Lucas, Nilendu Gupta, Allen Li, Beryl McCormick, Benjamin Smith, Rahul Tendulkar, Vivek Kavadi, Koji Matsumoto, Samantha Seaward, William Irvin, Jolinta Lin, Robert Mutter, Thierry Muanza, Jannifer Stromberg, Reshma Jagsi, Anna Weiss, Walter Curran, Norman Wolmark
Read the Full Article.
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