Toxicity of radiation and immunotherapy combinations

Although immunotherapy is a rapidly emerging modality for cancer care, there have been multiple reports of fatal toxicities. There have also been cases of treatment-related deaths with combined non-immunotherapeutic biologic compounds with radiation therapy. Thus, provision of summative information appraising the safety of combinatorial immunotherapy and radiation therapy (iRT) is imperative. Because this has not been well characterized, this review summarizes the available evidence to date.

Owing to the heterogeneity and relatively low quantity of published reports, this review was conducted in a narrative rather than systematic format.

The results of combined iRT, both concurrent and sequential, are discussed for oncologic therapy of the brain, lung, liver, and prostate. Most evidence is from small samples and shorter follow-up but does consist of multiple prospective publications. Most data exist for ipilimumab, with programmed cell death -1 inhibitors emerging in more recent years. With 2 large phase 3 trials as exceptions, there were no instances of iRT-related deaths across all discussed studies. Altogether, grade 3 to 4 toxicities were relatively low in frequency; of the studies that compared iRT with an "immunotherapy only" or "RT only" cohort, none documented a clear increase in high-grade adverse events with combined-modality management.

Despite the low quantity of data, combined iRT offers encouraging safety profiles. There is no evidence that iRT produces an overt increase in high-grade toxicities. Further data, especially on concurrent iRT, are anticipated from numerous iRT trials that are currently ongoing worldwide.