Receiving immune checkpoint inhibitor (ICI) treatment within 90 days after radiation therapy (RT) is not associated with an increased risk of adverse events (AEs) in cancer patients, according to research published in JAMA Oncology.

The 90-day time period after RT “classically represents the interval for manifestation of acute radiation-related injuries and may be a period of increased risk for AEs from additional systemic therapies,” the researchers noted.

To quantify that risk for ICIs, the researchers pooled data from 68 prospective trials in the US Food and Drug Administration database and analyzed a total of 16,835 patients.

The most common cancers in this cohort were bladder, head and neck, lung, and kidney cancer, as well as melanoma. Most patients (79.7%) were White, and 56.1% were younger than 65 years of age.

All patients received ICIs, including atezolizumab, avelumab, cemiplimab, durvalumab, ipilimumab, nivolumab, and pembrolizumab.

There were 13,956 patients who did not receive any RT, 1773 patients who received RT within 90 days prior to starting ICI treatment, and 1146 patients who received RT more than 90 days prior to starting ICI treatment.

The rates of AEs were generally similar between patients who did and did not receive RT. The average absolute difference in rates across the AEs was 1.2%, ranging from 0% for neurologic AEs to 8% for fatigue. For grade 3-4 AEs, the absolute difference ranged from 0.01% to 2%.

The most common AEs of any grade were:

  • Fatigue — occurring in 45.5% of the no-RT group, 53.1% of the RT ≤90 days group, and 44.4% of the >90 days RT group.
  • Diarrhea — 27.0%, 27.1%, and 19.5%, respectively
  • Endocrinopathies — 13.4%, 14.8%, 9.9%, respectively
  • Pneumonitis — 3.8%, 6.8%, and 3.6%, respectively.

AEs remained similar across the groups in a propensity score-matched analysis.

The researchers acknowledged limitations to this work, especially the fact that most of the trials analyzed were not designed to study the outcomes of combining RT with ICIs.

Future studies should focus on tissue dose volume guidelines, particularly with regard to organs known to be sensitive to immune-mediated AEs, such as the lungs and liver, according to the researchers. They also noted that follow-up studies are needed to address the safety of RT plus ICIs over the long term.

The researchers concluded that their findings “may help clinicians in the design of future trials testing concurrent or sequential combinations of ICIs and RT in the treatment of patients with advanced cancers.”


Anscher MS, Arora S, Weinstock C, 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. Published online January 6, 2022. doi:10.1001/jamaoncol.2021.6439