Higher shoulder joint radiation dose linked to worse arm morbidity in breast cancer patients with SLN macrometastases

BACKGROUND: Postoperative lymph node irradiation can affect shoulder morbidity in breast cancer patients, yet widely accepted dose-volume constraints for the shoulder joint are lacking. The SENOMAC trial randomized patients with breast cancer and 1-2 sentinel lymph node (SLN) macrometastases to axillary lymph node dissection (ALND) or SLN biopsy only. We aimed to analyze the association between the radiation dose to the shoulder joint and patient-reported arm morbidity one and three years after surgery using SENOMAC data. METHODS: Radiotherapy plans from 868 Swedish SENOMAC patients randomized 2015-2019 were collected. The humeral head was auto-segmented, and a 1 cm margin added to represent the shoulder joint. Arm morbidity was assessed using the Lymph-ICF questionnaire, focusing on questions regarding physical arm function and shoulder-related mobility tasks. RESULTS: The radiation dose was evaluable for 386 patients receiving ALND and 421 receiving SLN biopsy. The dose distribution to the shoulder joint was similar in both study groups. In the SLN group, a higher near-maximum dose (D) was associated with significantly worse arm morbidity scores three years after surgery, particularly among patients treated with breast-conserving surgery. No association was found in the ALND group. No dose thresholds for development of arm/shoulder related side effects could be identified. CONCLUSION: Our results indicate a possible association between maximum radiation dose to the shoulder joint and subsequent side effects. Extended follow-up within SENOMAC will provide further insights into the incidence of arm morbidity in relation to radiotherapy dose over time.