Adapting radiation therapy to immunotherapy: Delineation and treatment planning of pre-operative immune-modulating breast iSBRT in 151 patients treated in the randomized phase II Neo-CheckRay trial.

Abstract

The randomized multicentric phase II Neo-CheckRay trial investigated preoperative immune-modulating stereotactic body radiation therapy (iSBRT) 8 Gy x 3 fractions in combination with chemotherapy with or without the anti PD-L1 durvalumab and the anti-CD73 oleclumab in early-stage, high-risk, luminal B breast cancer. iSBRT was solely delivered to the primary breast cancer leveraging on its immune modulating potential to sustain an anti-tumour response. To avoid immunosuppression induced by radiation therapy (RT), the tumour draining lymph nodes (TDLN) were spared. Here, we present the constraints used in the Neo-CheckRay trial and a dosimetric analysis of all delivered treatment plans with a special focus on the dose to the TDLN. Main constraints were the skin (D0.1 cc < 19.2 Gy), chest wall (D1cc < 15 Gy) and ipsilateral uninvolved breast (V24Gy < 30 %). The dose to the TDLN was reduced by avoiding beams entering or exiting the TDLN. In the present work, the DICOM-RT data of all the patients treated in the Neo-CheckRay trial were collected (n = 151) to describe doses to the target volume, to the organs at risk and the TDLN. The TDLN volumes consisted of the internal mammary nodes (IMN) and the axilla levels I-IV including the interpectoral nodes. In 151 patients, the median V95% of the gross target volume (GTV) and planning target volume (PTV) were 97.4 % (90 % CI 26.5-100) and 95.5 % (56.1-100). The mean dose (dMean) to all TDLN volumes was < 1 Gy. The highest dMean were to the IMN and axilla level 1: 0.8 Gy (90 % CI 0.1-2.7) and 0.6 Gy (0.0-3.9), respectively. The dMean to the involved lymph nodes, if present, was 0.3 Gy (0.0-5.0). In the Neo-CheckRay trial, the predefined organs at risk dose constraints were feasible and the TDLN were adequately spared.