Combining Selective Internal Radiation Therapy with Immunotherapy in Treating Hepatocellular Carcinoma and Hepatic Colorectal Metastases: A Systematic Review

Abstract
Background: Immunotherapy in the form of checkpoint inhibitors has changed the treatment paradigm in oncology. Combining selective internal radiation therapy (SIRT) with immunotherapy has been suggested to potentially improve outcomes in hepatocellular carcinoma (HCC) and metastatic colorectal carcinoma (mCRC). In this systematic review, the authors discuss the current developments and available clinical data regarding the combination of immunotherapy and SIRT in treating hepatic malignancies. Methods: PubMed, Embase, and Cochrane library were systematically searched for eligible studies (adhering to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines). Original patient studies written in English language with patients with HCC or mCRC who were treated with SIRT and immunotherapy were included. Endpoints evaluated included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Results: 1038 publications were screened, from which 1034 publications were excluded. Eventually four studies with a total of 87 patients were included in this systematic review, of which two consisted of mCRC and the other two HCC. All four studies showed no increased toxicities of the combination therapy over known data on monotherapy. One mCRC study reported a median OS of 8 months, while the other mCRC study ended due to futility. Both reported an ORR of 0%. The two HCC studies reported a median OS of 16.5 and 16.2 months. Median PFS was 5.6 and 5.7 months. ORR ranged from 31% to 80%. Conclusion: The combination of SIRT and immunotherapy has been studied in four early-phase studies showing a favorable safety profile. Further studies are necessary to understand the possible synergy and possible benefit of combination therapy.