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SBRT is more and more commonly employed in the modern radiotherapy, including both primary tumor treatment and management of recurrent and metastatic disease. In all these scenarios systemic therapy is commonly used and in case of metastatic cancer systemic therapy remains a standard approch. There is an increasing number of new agents with heterogenous mechanisms of action and toxicity profile (immunotherapy, target therapy etc.) and only few of them have been formally studied in the combination with SBRT. Therefore the majority of data regarding efficacy and toxicity is coming from the retrospective series and prospective studies and registries (eg. ESTRO EORTC Oligocare Consortium). Althought the preclinical data suggest improved radiotherapy efficacy when new agents are added to SBRT, this effect has not been universally showed in clinical trials. From the toxicity point of view, the majority of side effects are striclty correlated to new drugs and outside SBRT volume. Contradictory data on the pausing rules have been published, with no clear negative effects of pausing. Importantly, different half-lives of target therapy (ranging from 24h to 50 days) request different pausing interval between drug and SBRT. So far very favorurable toxicity profie has been seen for the following combinations: 1) RT + endocrine therapy (both standard and new generation agents); 2) RT + HER2 agents, 3) RT + immunotherapy (Meattini I et al. 2022, Anscher et al. 2022), . The recent pooled analysis of FDA database (16,835 patients treated with RT and immunotherapy) showed that administration of immunotherapy within 90 days following RT was not associated in any increase in toxicity apart from fatigue level in (Anscher 2022). Contrarily, somehow higher toxicity has been been reported for the combinations of RT and bevacizumab, TKI, BRAFi, MEKi, PARPi, CDK4/6i, mTORi, therefor interruption of the systemic therapy in these cases has been wildely suggested. The ongoing initiative and trials will help to define the best strategies to combine safely SBRT and systemic therapies (Kroeze et al. 2023).
1.    Anscher MS, et al. Association of Radiation Therapy With Risk of Adverse Events in Patients Receiving Immunotherapy: A Pooled Analysis of Trials in the US Food and Drug Administration Database..JAMA Oncol. 2022 Feb 1;8(2):232-240. doi: 10.1001/jamaoncol.2021.6439
2.    Kroeze SGC, et al. Metastases-directed stereotactic body radiotherapy in combination with targeted therapy or immunotherapy: consensus recommendations by the EORTC-ESTRO OligoCare Consortium. Lancet Oncol in press
3.    Meattini I, et al. Integrating radiation therapy with targeted treatments for breast cancer: From bench to bedside. Cancer Treat Rev. 2022 Jul;108:102417. doi: 10.1016/j.ctrv.2022.102417. Epub 2022 May 21.