Reporting of late morbidity after radiotherapy in large prospective studies: A descriptive review of the current status

Abstract Introduction The purpose of this review was to evaluate the current status of reporting prospectively assessed late morbidity after curative radiotherapy in large clinical studies. Material and methods A descriptive review on publications from 10 high impact journals with a primary or partial focus on radiotherapy published between 12/01/2015 and 11/30/2017 was conducted. Publications were considered eligible if they reported prospectively assessed late morbidity after curative radiotherapy and included ≥200 patients with cancer of any type. Full text publication and supplementary material were analyzed according to items based on extensions to the “Consolidated Standards of Reporting Trials” (CONSORT) statement regarding reporting of harms and patient reported outcomes (PROs). Results Overall, 802 publications were identified in PubMed; of these 69 met the eligibility criteria. Mild and moderate morbidity were reported in 40% and 57% of publications; aggregated endpoints instead of individual endpoints were reported in 23%. In 43% of publications, crude incidence of worst grade of morbidity was used as the only statistical method for summarizing physician-assessed morbidity. Duration of morbidity or recurrent events were not reported in any of the publications. Conclusion Comprehensive, quantitative reporting of late morbidity after radiotherapy is challenging due to the high dimensionality and time evolution of the range of normal tissue effects. The following recommendations/suggestions are proposed: 1) To report on individual severity grades, including moderate and mild, 2) To utilize PROs in complement to physician-assessed morbidity, 3) To report on individual symptoms/endpoints on top of aggregated endpoints 4) To report on duration of morbidity or recurrent events, 5) To take steps towards a consensus on severity grading scales/patient questionnaires, 6) To utilize time to event analysis and prevalence rates, 7) To report or use statistical methods accounting for pre-treatment morbidity when relevant.