Toxicity outcomes of concurrent radiotherapy with adjuvant capecitabine in triple-negative breast cancer (TROD 06-24)

Triple-negative breast cancer (TNBC), the subtype with the poorest prognosis, shows treatment outcomes closely tied to the response to neoadjuvant chemotherapy. Patients with residual disease post-treatment face a higher recurrence risk. In this subgroup, adjuvant capecitabine has been shown to improve disease-free and overall survival. Although concurrent use of capecitabine and radiotherapy (RT) is considered safe in gastrointestinal cancers, data on its safety in breast cancer are limited. This study aimed to evaluate toxicity outcomes associated with concurrent capecitabine and RT in TNBC. This retrospective multicenter study included 95 patients with TNBC treated with concurrent adjuvant capecitabine and RT between 2018 and 2024 across eight medical centers. Toxicity was graded according to CTCAE v5.0. Univariable comparisons were adjusted for multiple testing using the Benjamini-Hochberg false discovery rate. Multivariable analyses were performed using forward stepwise logistic regression for grade 2–3 dermatitis and Firth’s penalized likelihood logistic regression for grade 3 dermatitis. Statistical analyses were performed using Jamovi 2.6.44, JASP 0.19.3, and Python 3.11. The median follow-up was 25.3 months, and the median age was 49 years (range 29–81). Comorbidities were present in 33.7% of patients. RT was interrupted in 5.3% of patients; capecitabine was dose-reduced in 5 patients and discontinued in 2. Skin toxicity occurred in 86.3% of patients (grade 1, 44.2%; grade 2, 33.7%; grade 3, 8.4%), while 13.7% experienced no skin toxicity. Hematologic toxicity (any grade) was observed in 26.3% of patients and gastrointestinal toxicity in 8.4%, with no significant differences across skin toxicity strata. After multiplicity adjustment, clinical T3–4 stage, post-neoadjuvant ypT3-4 and ypN2-3 stage, and bolus application were significantly associated with higher-grade dermatitis (all q < 0.05). On multivariable analysis, advanced clinical T stage was the sole independent predictor of grade 2–3 dermatitis (OR 4.62, 95% CI 1.80-11.91, p = 0.002). For grade 3 dermatitis, Firth penalized regression identified total lymphatic irradiation (OR 9.93, p = 0.006) and bolus application (OR 7.08, p = 0.036) as independent predictors. Concurrent capecitabine and RT in TNBC demonstrated a manageable acute toxicity profile in this retrospective multicenter cohort. Further prospective studies are needed to validate these findings.