Interventional radiation immune-boosting (iRIB). The role of concomitant interventional radiotherapy (modern brachytherapy) in immunotherapy: A hypothesis-generating systematic review.

Purpose: Synergistic activity of radiation and immunotherapy is well known to the extent that it can be referred to as radiation immuno-boosting. Interventional radiotherapy (IRT; modern brachytherapy) has a potential immunomodulatory advantage compared with external beam radiotherapy due to highly conformal dose distribution and dose heterogeneity, engaging multiple immunogenic mechanisms with distinct dose-response profiles. Material and methods: A hypothesis-generating systematic review was conducted in June 2026 using PubMed/MEDLINE, Scopus, and Web of Science databases to identify clinical studies reporting outcomes of patients treated with IRT plus immunotherapy, including any primary tumor, assessing efficacy and toxicity. Study selection, data extraction, and risk of bias assessment were performed according to PRISMA 2020 guidelines, and certainty of evidence was evaluated using a GRADE-based approach. Among the identified publications, 13 studies were included in qualitative synthesis. Results: The included studies published between 2019 and 2026 were non-randomized, and comprised 98 patients with hepatocellular carcinoma, adrenocortical carcinoma, melanoma, kidney, and pancreatic or lung cancer. IRT was delivered before, concurrently, or in close temporal proximity to immunotherapy. Radiological tumor response of irradiated lesions was consistently reported, although outcome definitions were heterogeneous and often descriptive. Progression-free survival ranged from 1 to over 30 months. Severe treatment-related toxicity (grade ≥ 3) was uncommon, and no unexpected safety signals were observed. Occasional regression of non-irradiated lesions was reported; however, these observations were anecdotal and cannot be reliably attributed to radiation-induced systemic immune activation. Conclusions: Interventional radiotherapy has a biological rationale for potential immunomodulatory interactions with immunotherapy, but these effects have not yet been established clinically. Although current clinical evidence is limited and of very low certainty, preliminary findings support additional prospective investigation. Further prospective studies are required to better characterize the optimal integration of IRT and immunotherapy, including radiation dose, fractionation schedules, and treatment sequencing.