OPTimizing Irradiation through Molecular Assessment of Lymph node (OPTIMAL): a randomized clinical trial.

Abstract

In breast cancer (BC) patients, the involvement of four or more lymph nodes (LN) is an indication of regional irradiation. The optimal treatment strategy remains unclear when fewer nodes are involved and lymphadenectomy is not performed. We designed a clinical trial to show the non-inferiority of Incidental (INC) compared to intentional (INT) irradiation of axillary nodes in patients with early-stage BC and low burden LN involvement. BC patients, cN0 (n = 487) undergoing breast conservation surgery and sentinel node biopsy, with total tumor load assessed by OSNA (One-Step Nucleic Acid Amplification) of 250-15,000 copies mRNA CK19/µL in sentinel LN were randomized to receive INC or INT nodal irradiation. The primary endpoint was 5-year disease-free survival (DFS). Secondary endpoints were locoregional recurrence (LRR), distant recurrence (DR), and acute and chronic toxicity (CT). Five-years DFS were 93.7% (INC) and 93.8% (INT) (difference 0.1% [one-sided 95% CI Intentional does not outperform incidental irradiation by more than 5.7% in terms of 5-year DFS, 4.8% for LRR, and 6% for DR. ClinicalTrials.gov Identifier: NCT02335957.