Radiotherapy in Patients Undergoing Breast-Conserving Surgery With or Without Axillary Sentinel Lymph Node Biopsy: Secondary Analysis of the INSEMA Trial

The de-escalation of axillary surgery during breast-conserving surgery (BCS) must be evaluated in the context of radiotherapy (RT) to fully understand oncological outcomes. The INSEMA trial demonstrated that omitting sentinel lymph node biopsy (SLNB) in patients with clinically node-negative, early breast cancer undergoing BCS is oncologically safe with respect to 5-year invasive disease-free survival (IDFS). However, findings from other de-escalation trials (eg, ACOSOG Z0011, SENOMAC) have shown that a significant proportion of patients received regional nodal irradiation (RNI), which may influence outcomes. The INSEMA trial documented dose distribution to ipsilateral axillary levels 1 to 3 and the use of RNI. This article summarizes the secondary analysis investigating how patient characteristics, the extent of axillary surgery, and RT techniques affect ipsilateral axillary dose.

INSEMA (NCT02466737) is a surgical trial assessing SLNB omission in patients with early invasive breast cancer undergoing BCS. Between September 2015 and April 2019, 5502 patients were randomized in Germany and Austria. The trial protocol mandated whole-breast irradiation (WBI) for all patients; RNI was only permitted for patients with ≥4 involved lymph nodes. This preplanned secondary analysis includes 5154 patients treated at 108 RT facilities. Axillary levels 1 to 3 were contoured according to the Radiation Therapy Oncology Group consensus definitions. Dose parameters were reported as relative percentages of the prescribed breast dose to account for differences between conventional and hypofractionated cases.

Among the 5154 patients analyzed, 4858 received postoperative WBI as per protocol. The majority (n=2800, 58.0%) were treated with 3D-conformal RT using standard tangential fields; others received advanced intensity-modulated RT techniques. Deep inspiration breath hold was utilized in 102 patients (2.1%). Conventional fractionation was more common (n=3163, 66.0%) compared with moderate hypofractionation (n=1630, 34.0%). A tumor bed boost was applied in 78% of patients. No differences were observed between the randomized groups regarding the RT technique, fractionation schedules, or boost application.

Median and average doses to axillary levels differed significantly between groups, with higher median doses observed in the SLNB arm compared with the non-SLNB arm: level 1 (91.3% vs 86.3%, P<.001) and level 2 (37.8% vs 23.3%). RNI, including irradiation of supraclavicular, infraclavicular, and/or parasternal nodes, was performed in 4.1% of patients in the SLNB arm versus 0.6% in the non-SLNB arm (P<.001). Among 264 patients who did not receive postoperative RT, IDFS did not significantly differ between the non-SLNB and SLNB arms (hazard ratio, 1.47; 95% CI, 0.75-2.85; P=.26).

Approximately 50% of INSEMA patients received a potentially therapeutic dose to axillary level 1, even in the absence of explicit RNI. Patients in the SLNB arm had higher incidental axillary doses and a greater use of RNI compared with the non-SLNB arm, where RNI was applied in <1% of patients. These findings highlight the impact of surgical and RT practices on axillary dose distribution and their potential implications for oncological outcomes.

Source: Hildebrandt G, Stachs A, Veselinovic K, et al. Insights of applied radiotherapy among patients undergoing breast-conserving surgery with or without axillary sentinel lymph node biopsy: secondary results from the INSEMA trial. Presented at: San Antonio Breast Cancer Symposium 2025. December 11, 2025; San Antonio, TX. Presentation GS2-03.