Complicated response.

Top Line: An open question in radiation oncology is how the response to neoadjuvant therapy for breast cancer should influence the use of adjuvant radiation–particularly regional nodal irradiation (RNI).

The Study: Currently, adjuvant radiation is guided by the initial extent of disease. This study compiled data from 4 large randomized trials of neoadjuvant systemic therapy spanning decades to explore potential indications and outcomes for RNI. For a brief review, in NSABP B-18, patients received 4 cycles of doxorubicin and cyclophosphamide (AC) before or after surgery. B-27 tested the addition of docetaxel to neoadjuvant AC. In B18 and B27, RNI was not allowed. Also, nobody received HER2 targeted therapy, and endocrine therapy was used irrespective of receptor status. B-40 tested 3 different docetaxel-based neoadjuvant regimens in HER2- patients, and B-41 added paclitaxel and HER2-targeted therapy to neoadjuvant AC in HER2+ patients. RNI was allowed in B-40 and B-41 at physician discretion. First off, the study confirmed the well-established fact that patients with residual disease in the breast or axilla after neoadjuvant chemo have inferior outcomes. And when it came to locoregional recurrence (LRR), patients with triple-negative subtype and any residual disease had >10% risk at 5 years while those with HER2+ subtype and residual axillary disease had ~10% risk at 5 years. It was important to note that discretionary use of RNI in B-40 and B-41 was biased towards patients with large tumors, clinically positive nodes, and residual disease in the breast and/or axilla. With that in mind, there was a trend toward improved LRR with RNI, but ultimately no significant difference. But because RNI was discretionary, it isn’t possible to know if those patients would have done worse without RNI. In contrast, those with complete response to neoadjuvant therapy had a very low risk of LRR.

TBL: RNI after neoadjuvant systemic therapy remains a gray zone where patient, disease, and response characteristics influence the risk of LRR and the potential benefit of treatment. | Mailhot Vega, Int J Radiat Oncol Biol Phys 2022

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