ESTRO 2024 - Abstract Book

S56

Invited Speaker

ESTRO 2024

The talk will provide an overview of this important field of research.

3370

Is less axillary surgery safe in irradiated, high-risk breast cancer patients: Results from the SENOMAC trial

Jana de Boniface

Capio St. Göran's Hospital, Department of Surgery, Breast Unit, Stockholm, Sweden. Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden

Abstract:

Is less axillary surgery safe in irradiated, high-risk breast cancer patients: Results from the SENOMAC trial

Background

The omission of a completion axillary lymph node dissection (cALND) after a positive sentinel lymph node (SLN) biopsy in patients with clinically node-negative breast cancer has been demonstrated to yield survival outcomes non-inferior to routine cALND in breast-conserving surgery followed by whole-breast irradiation (ACOSOG Z0011 and IBCSG 23 01 trials), and to axillary radiotherapy (RT) regardless of breast surgery (EORTC AMAROS trial). Mainly due to the under-representation of mastectomy patients, a limited number of observed events compromising statistical power, and uncertainties regardiing the exact RT volumes in these trials, the international randomized SENOMAC trial was initiated in 2015. The main aim of this non-inferiority trial was to address knowledge gaps relating to individuals treated by mastectomy, those with larger tumors and those with SLN extracapsular extension. The SENOMAC trial is a noninferiority trial randomizing patients with clinically node-negative primary T1-3 breast cancer with 1-2 SLN macrometastases 1:1 to cALND or its omission (sentinel node biopsy only). Adjuvant treatment and RT were given in accordance with national guidelines. The primary endpoint is overall survival; pre-specified secondary endpoints are overall survival, breast cancer-specific survival, patient-reported quality of life and arm morbidity, and the here reported fully powered endpoint of recurrence-free survival. Whole-breast radiation therapy after breast-conserving surgery was mandatory. Radiation therapy boost to the tumor bed, post-mastectomy and regional radiation therapy were in accordance with national guidelines. Radiation therapy quality control was performed as a source data verification, comparing registered eCRF data with actual radiation therapy plans, for all patients randomized in Sweden or Denmark until May 31, 2019. Statistical sample size calculation was based on the primary outcome overall survival. Clinical noninferiority was defined as a 5-year OS not worsened by more than 2.5% when omitting cALND. This margin was intentionally small, i.e. half of the margin used in ACOSOG Z0011, to increase clinical applicability. Thus, 190 deaths need to be observed, with a one-sided α of 10% and a power of 80%. This corresponds to the upper one-sided 90% confidence interval for the hazard ratio (HR: SLN biopsy only/cALND) falling below 1.44. For the here reported secondary endpoint of recurrence-free survival, sample size calculation assumed a 5-year RFS of 90% for cALND based on the safety analysis of May 2020. With an unchanged HR of 1.44, resulting in a pre-specified noninferiority margin of 4.1%, the trial reached sufficient power (80%) to conclude noninferiority once 190 recurrence-free survival events had occurred. Methods