Treatment de-escalation for early-stage breast cancer: MRI-guided single dose preoperative ablative radiotherapy

Abstract

Breast cancer is the number one oncological burden in women across the globe. Given the increase breast cancer survivorship and knowledge on side effects of cancer therapies, patient reported outcomes have gained importance. A treatment ought not to be solely oncologically effective, but also have a limited impact on the patient’s physical and emotional wellbeing. The goal of the current thesis was to set-up and evaluate a new de-escalating treatment approach for early-stage low-risk breast cancer, namely MRI-guided single dose preoperative ablative radiotherapy. In practical terms, this treatment approach has the potential to omit a surgical treatment and/or replace the protracted 15-daily fractions radiotherapy schedule during 3 weeks for future patients. Firstly, the impact of standard of care multiple fractionated postoperative radiotherapy was evaluated in breast cancer patients above 60 years of age, illustrating impaired physical functioning and fatigue up to 6 months. Furthermore, a comparative dosimetry study was performed on the most suitable radiotherapy technique (i.e. multi-catheter interstitial brachytherapy versus volumetric modulated arc therapy (VMAT)) before initiating the first prospective clinical study on MRI-guided single dose preoperative ablative radiotherapy for early-stage breast cancer (ABLATIVE-study) using a VMAT-approach. Since solely mild toxicity was encountered in the first patients, guidelines for adequate tumor coverage and dose constraints for healthy organs were set up in collaboration with an American oncological centre. The last part of the thesis evaluates the single dose approach as dosimetrically feasible on the MRI-linac – a hybrid system consisting of a radiotherapy delivery system and an MRI-scanner enabling tumor visualization during treatment. The current thesis concludes that MRI-guided single dose preoperative ablative radiotherapy has great potential to become a de-escalating, though oncological effective approach for low-risk early-stage breast cancer.