Partial Breast Re-irradiation for Breast Cancer

Overview

Breast cancer is the most common malignancy in women. Breast-conserving surgery (BCS) with adjuvant whole-breast irradiation (WBI) is currently the standard of care in the oncological treatment of primary breast cancer and offers an equivalent alternative to mastectomy. The primary aim of adjuvant radiotherapy (RT) is to improve local control and thus improve overall survival and breast cancer-specific mortality. However, nodal-negative women have a 10-year risk for local recurrences after RT in up to 15.6%. The management of ipsilateral breast cancer recurrence depends on the extent of tumor disease and staging results at the time of recurrence and mastectomy is currently the standard of care for previously irradiated patients. The application of particle therapy using proton beam therapy (PBT) represents an innovative radiotherapeutic technique for breast cancer patients. This trial will be conducted as a prospective single-arm phase II study in 20 patients with histologically proven invasive breast cancer recurrences with negative margins after repeat BCS and with an indication for local re-irradiation. Required time interval will be 1 year after previous RT to the ipsilateral breast. Patients will receive partial breast re-RT with proton beam therapy in 15 once daily fractions up to a total dose of 40.05 GyRBE. The primary endpoint is defined as the cumulative overall occurrence of acute / subacute skin toxicity grade ≥3 within 6 months after the start of re-RT.

The therapeutic challenge in re-irradiation involves finding a balance between tumor control and the risk of severe toxicity from cumulative radiation doses in previously irradiated organs. Re-RT options include the use of brachytherapy (BT) \], intraoperative radiotherapy (IORT) or external beam RT with photons or electrons. Depending on the time interval since previous RT and applied technique, high-grade (≥3) toxicity rates for re-RT range from about 9% acute skin to 12 % - 17 % late fibrosis and 1% - 10 % G4 toxicity for BT, late grade 3 fibrosis of 21% for IORT and grade 3 toxicity (skin, esophagitis, wound dehiscence) of 7 - 24% - 35% for EBRT including late breast volume asymmetry in 12%, acute and late grade 4 ulceration (1-2%) and even grade 5 (treatment related deaths) in 1.2%. The dosimetric profile of PBT with the Bragg Peak offers advantageous physical properties and has proven to be superior to photon-based techniques in respect of dose reduction to adjacent organs-at-risk (OAR) and effective target volume coverage with lower integral doses to the patient's whole body. In addition, this technique could potentially offer higher radiobiological effects and tumor responses \[28\], which is particularly advantageous in potentially more therapeutically resistant disease biology in breast cancer recurrences. Overall, prospective experience related to re-RT of the ipsilateral breast after recurrences is limited and most commonly involves the technique of invasive multicatheter brachytherapy.