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Purpose  The features of past and contemporary phase III clinical trials for radiotherapy were reviewed to activate future clinical trials and to advise on actual clinical practice.    Methods and materials  The phase III clinical trials for radiotherapy were searched in the database of ‘ ClinicalTrials.gov ’ by the U.S. National Institute of Health. Using the staring date, the studies during each period of 4 years were collected for the past (from Jan 2000 to Dec 2003) and contemporary (July 2014 to June 2018) years. For the investigated subjects, the patterns of studies were classified as: Category A, the comparisons of rival radiotherapy protocols; Category B, the comparisons of multidisciplinary approaches; Category C, the investigation of supplementary agents; and Category D, the investigation of optimal partners for concurrent radiotherapy.    Results  The number of studies increased, from 96 past to 158 contemporary studies. The patterns of studies were similar with the mild increase of Category A in the contemporary years (22.9% vs. 29.1%). For the study locations and the funding sources, the Chinese studies (2.1% vs. 34.2%,  P  < 0.001) and the affiliated institutions of researchers (37.5% vs. 72.2%, P < 0.001) markedly increased in the contemporary years from the past Western studies and non-profit organization, respectively. The robust radiation techniques were more usual in the contemporary years (11.5% vs. 44.9%,  P  < 0.001). The fractionation schedule and delivery technique were the common issues in both past and contemporary years of Category A. In Category B, the indications of stereotactic radiotherapy was the rising concern, with eight ongoing studies. Except for the studies of palliative or prophylactic goals and stereotactic radiotherapy, the escape from conventional fraction size was 37.9% (36/95) in the contemporary years with the median fraction size of 2.5 Gy (range 2.05–6.6 Gy) in the comparison with 19.0% (15/79) in the past years ( P  = 0.006).    Conclusions  To activate the clinical trials for radiotherapy, the funding sources would be diversified, including industrial support. Hypofractionated schedules using robust techniques could be preemptively considered in actual clinical practice.

Where is clinical research for radiotherapy going? Cross-sectional comparison of past and contemporary phase III clinical trials