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Approximately 5-10% of women present de novo metastatic breast cancer (MBC). Even if current literature data do not support loco-regional treatment in all patients, some of the study results suggest that there is a subset of patients who might benefit from radical locoregional treatment especially those patients who have significantly improved survival with the available new effective target agents. Potential advantages of stereotactic ablative radiotherapy (SABRT) in treating breast primary tumor in metastatic breast cancer relies on the radio-biological advantage of a short highly effective treatment schedule, the possibility of continuing systemic treatment without interruption and of treating symptomatic lesions. We developed a prospective dose escalation trial to evaluate  the maximum tolerated dose of SABRT to primary breast cancer in this setting

Patients with histologically confirmed diagnosis of invasive breast carcinoma (biological immunohistochemical profile: luminal and/or HER2 positive) and distant metastatic disease not progressing after 6 months of systemic therapy with a tumor CT or 5FDG-PET detectable were deemed eligible. The starting dose was 40 Gy in 5 fractions (level 1) because this dose proved to be safe in previous dose-escalation trial on adjuvant stereotactic body radiotherapy. The maximum dose level was chosen as 45 Gy in 5 fractions. Dose limiting toxicity was any grade 3 or worse toxicity according to CTCAE v.4. Time-to-event Keyboard (TITE-Keyboard) design (Lin and Yuan, Biostatistics 2019) was used to find the maximum tolerated dose (MTD). MTD was the dose of radiotherapy associated with a ≤ 20% rate pre-specified treatment-related dose –limiting toxicity (DLT).

To date 10 patients have been treated at the starting dose level. Median age was 80 years (range 50-89). 7 patients had a luminal disease while 3 patients had an HER2 positive disease. No patient suspended current systemic treatment. No protocol defined DLTs were observed. When examining AEs,  grade 2 skin toxicity occurred in 4 patients with diseases located next to the skin and showing clinical retraction.  All 10 patients, with a minimum follow-up of 6 months, were evaluable for response: 3 achieved a complete response, 6 achieved a partial response and 1 showed a stable disease with a clinical benefit (resolution of skin retraction). The mean reduction in the sum of the largest diameters of target lesions was of 61.4% (DS=17.0%). In all patients with a skin retraction, retraction disappeared after treatment.

SABR to primary breast cancer seems feasible and associated with symptoms reduction. Continued accrual to this study is needed to confirm the safety and assess the MTD.