Definitive single-fraction ablative radiotherapy for early-stage breast cancer: DESERT-I trial – a dose-escalation study protocol

There is a growing trend toward more tolerable and less aggressive treatments for breast cancer patients. For low-risk patients, accelerated partial breast irradiation (APBI) following conservative surgery is a widely used treatment. However, partly due to the development of modern techniques such as stereotactic ablative radiation therapy (SABR), the use of radiotherapy in breast cancer as a neoadjuvant approach has been gaining relevance in recent years. Given the promising results reported in several studies, the use of SABR as a definitive treatment for breast cancer warrants further investigation. The DESERT-I trial is a prospective dose-escalation study designed to evaluate 5 dose levels of definitive single-dose ablative radiotherapy in patients with early-stage breast cancer. Eligible patients must have confirmed non-lobular invasive breast cancer that meets the following characteristics: unifocal, estrogen receptor-positive, HER2-negative, tumor size smaller than 3 cm and clinically negative axillary staging. The primary objective of the study is to determine the maximum tolerated dose by assessing dose-limiting toxicity across 5 cohorts: 20 Gy, 23 Gy, 26 Gy, 28 Gy, and 30 Gy. Secondary objectives include evaluating chronic toxicity, quality of life, cosmetic outcomes, pathological response (assessed via core biopsy at 6 and 12 months post-treatment), radiological response (evaluated through MRI or contrast-enhanced mammography at 12 months post-treatment), and analyzing biomarkers and tumor microenvironment in liquid biopsy and tumor tissue. The use of definitive radiotherapy in breast cancer remains a largely uncharted area. Currently, the optimal radiation dose required to achieve the best oncological outcome with acceptable toxicity is unknown. The DESERT-I clinical trial aims to determine the maximum tolerated dose across 5 different cohorts, with the goal of using this safe dose in a larger patient population in the phase II study. Additionally, the trial will analyze biomarkers and study tumor microenvironment using both liquid biopsy and tumor tissue. These findings could lay the groundwork for better patient selection and the future combination of SABR with immunotherapy. This trial was registered on 4th November 2024 with ClinicalTrials.gov Identifier: NCT06671691.