Kick in the pants.

Top Line: One of the most pressing research issues recognized by oncologists is the integration of radiation and immunotherapy, and here we have two studies looking at just that.
The Study: The first is a combined analysis of three Phase 1/2 trials of combined immunotherapy and thoracic radiation. The included trials evaluated ipilimumab with stereotactic body radiation (SBRT) for lung mets, pembrolizumab with definitive or consolidative radiation for small cell lung cancer, and pembrolizumab with SBRT or palliative radiation for lung mets. There are two major takeaways. First, there were very few grade 4 lung events, and they didn’t appear to be associated with concurrent immunotherapy. Instead, the rate of grade 4 events were much more related to the size of the target volume. There was no grade 4 toxicity with SBRT, while limited-volume palliative radiation and especially larger-volume definitive radiation had higher rates. The second report was of the phase 1 PLUMMB trial that combined pembro and radiation for advanced or metastatic bladder cancer with the hopes of generating an abscopal effect. The radiation regimen was 6 Gy once per week for 6 weeks for 36 Gy total. The trial was stopped early after dose limiting toxicities occurred in 2 of the first 5 patients with two cases of severe cystitis and one rectal perforation. Oy.
Bottom Line: Despite a widespread concern for lung toxicity, concurrent radioimmunotherapy may carry a scarier risk of pelvic toxicity. At least with 6 Gy a pop. | Verma, Int J Radiat Oncol Biol Phys 2018 and Tree, Int J Radiat Oncol Biol Phys 2018

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