Purpose: In the past decade, immune checkpoint inhibitors (ICIs) have emerged as a treatment option for metastatic breast cancer (BC). More recently, ICIs have been approved in the perioperative setting. This has led to clinical scenarios where radiation therapy (RT) is given concurrently with ICIs. On the other hand, moderate- and ultra-hypofractionated (HF) schedules of RT are being widely adopted in the adjuvant setting, in addition to an increased use of metastasis-directed therapy. Furthermore, RT can modulate the tumor microenvironment and induce a systemic response at non-irradiated sites, ‘abscopal effect’. The amplification of anti-tumor immune response is used as the rationale behind the concomitant use of ICIs and RT. To date, there is a lack of literature on the optimal sequence, timing, dose/fractionation schema and treated RT volumes with ICIs in patients with BC, especially in the era of HF. Methods and Materials: We conducted a systematic review to delineate the reported treatment details, safety and efficacy of combiningICI and RT in patients with BC. Pubmed, Embase and Cochrane CENTRAL were searched up between 2014-2023. Data was extracted to assess the details of ICIs/RT delivery, safety and efficacy. Results: Of the twelve eligible studies, nine involved patients with metastatic BC. Most studies were phase 1/2, had a small sample size (range 8-28) and were heterogenous in patients’ population and reported outcomes. The combination was reported to be safe. We identified one study in the perioperative setting, which did a post-hoc analysis of safety/efficacy of ICIs in the adjuvant setting with receipt and pattern of RT. Conclusions: In conclusion, there is limited data on the dose, timing, fractionation, volumes of RT in both the adjuvant and metastatic setting in BC. The ongoing/future trials should collect and report such data on RT details, whenever RT is used in combination with ICIs.

International Journal of Radiation Oncology, Biology, Physics

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