Evaluation of Clinical Trials Addressing Supportive Care Measures for Acute and Chronic Radiation Toxicities

Abstract

Despite advances in treatment delivery techniques, a variety of acute and late side effects secondary to radiation therapy occur. Significant research efforts have focused on preventing occurrence of toxicity; however, there is continued demand for evidence-based supportive care measures to treat radiation side effects. The purpose of this analysis is to characterize the state of supportive care trials in radiation oncology and to identify areas needing further study. Clinicaltrials.gov was queried using the search term “radiation toxicity” to identify past and current registered trials with a primary endpoint of toxicity management. To evaluate the proportion of supportive care trials, studies were classified as toxicity prevention or as supportive care interventions. Information regarding country of origin, trial era, study phase, disease site, toxicity evaluated, intervention, industry sponsorship, single- vs. multi-institutional status, sample size, and the use of patient-reported outcomes were evaluated for all supportive care trials. A total of 223 trials were identified. After exclusion of terminated trials or trials focused on radiation techniques (e.g., 3D-CRT vs. IMRT, protons), 71 studies met the criteria of either radiation toxicity prevention (n = 50) or supportive care (n = 21). Fourteen of these trials were active (8 prevention, 6 supportive care), with the remainder inactive, unknown, or complete. Within the group of 21 supportive care trials, the design included randomized phase III interventions in 6 studies (29%) with the remainder phase II (n = 4, 19%), phase I/II (n = 1, 5%), phase I (n = 1, 5%), or observational/uncategorized (n = 9, 43%). The most common disease site studied was head and neck (n = 6, 29%), followed by CNS (n = 3, 14%). Xerostomia, mucositis, and neurocognitive function (n = 3, 14% each) were the most commonly evaluated toxicities. The majority of studied interventions (n = 11, 52%) were medications with hyperbaric oxygen and diet as the next most common (n = 3, 14% each). Twelve trials were single institution (57%) and the median sample size was 91 (range: 11 to 320). Twelve studies included patient-reported outcomes (PROs), of which 7 trials (33%) had PROs as a primary endpoint. While numerous studies evaluating toxicity reduction exist, effective management of radiation-related toxicities remains important to promote quality of life during and after radiation therapy. There are few supportive care trials in radiation oncology and only a small portion of these are currently designed to generate level I evidence to evaluate interventions. There is a significant need for well-designed supportive care trials with patient-reported endpoints to guide management of radiation toxicity.