Persistence of Late Substantial Patient-Reported Symptoms (LAPERS) After Radiochemotherapy Including Image Guided Adaptive Brachytherapy for Locally Advanced Cervical Cancer: A Report From the EMBRACE Study.

PURPOSE: This report describes the persistence of late substantial treatment-related patient-reported symptoms (LAPERS) in the multi-institutional EMBRACE study on magnetic resonance image guided adaptive brachytherapy in locally advanced cervical cancer (LACC). METHODS AND MATERIALS: Patient-reported symptoms (European Organization for Research and Treatment of Cancer [EORTC]-C30/CX24) and physician-assessed morbidity (Common Terminology Criteria for Adverse Events [CTCAE], version 3.0) were assessed at baseline and regular timepoints during follow-up. Patients with sufficient EORTC follow-up (baseline and ≥3 late follow-up visits) were analyzed. LAPERS events were defined as the presence of substantial EORTC symptoms (quite a bit/very much) for at least half of the assessments (persistence) and progression beyond baseline condition (treatment-related). For each EORTC symptom, the ratio between LAPERS rates and crude incidence rates of substantial symptoms was calculated to represent the proportion of symptomatic patients with persisting symptoms. For 9 symptoms with a corresponding EORTC/CTCAE assessment, the overlap of LAPERS and severe morbidity events (grades 3-5) was evaluated. RESULTS: Of 1047 patients with EORTC available, 741 had sufficient follow-up for the LAPERS analyses. The median follow-up was 59 months (interquartile range, 42-70 months). Across all symptoms, the proportion of patients with LAPERS events (LAPERS rates) was in median 4.6% (range, 0.0% vaginal bleeding to 20.4% tiredness). Urinary frequency, neuropathy, fatigue, insomnia, and menopausal symptoms revealed LAPERS rates of >10%. Vomiting, blood in stool, urinary pain/burning, and abnormal vaginal bleeding displayed LAPERS rates of <1%. A median of 19% of symptomatic patients (interquartile range, 8.0%-28.5%) showed persistent long-term symptoms (LAPERS events). In symptoms with a corresponding EORTC/CTCAE assessment, 12% of LAPERS events were accompanied by a severe CTCAE event. CONCLUSIONS: Within this large cohort of survivors of LACC, a subgroup of patients with persistent symptoms (LAPERS events) was identified. For symptoms with a corresponding EORTC/CTCAE assessment, the vast majority of LAPERS events occurred in patients without corresponding severe physician-assessed morbidity. These findings emphasize the importance of distinguishing between transient and persisting symptoms in the aftercare of LACC survivors.

Reporting of Late Morbidity After Radiation Therapy in Large Prospective Studies: A Descriptive Review of the Current Status.

PURPOSE: The purpose of this review was to evaluate the current status of reporting prospectively assessed late morbidity after curative radiation therapy in large clinical studies. METHODS AND MATERIALS: A descriptive review on publications from 10 high-impact journals with a primary or partial focus on radiation therapy published between December 1, 2015, and November 30, 2017, was conducted. Publications were considered eligible if they reported prospectively assessed late morbidity after curative radiation therapy 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. 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. CONCLUSIONS: Comprehensive, quantitative reporting of late morbidity after radiation therapy is challenging because of the high dimensionality and time evolution of the range of normal tissue effects. The following suggestions and recommendations are proposed: (1) report on individual severity grades, including moderate and mild; (2) use patient reported outcomes in complement to physician-assessed morbidity; (3) report on individual symptoms/endpoints on top of aggregated endpoints; (4) report on duration of morbidity or recurrent events; (5) take steps toward a consensus on severity grading scales/patient questionnaires; (6) use time to event analysis and prevalence rates; (7) report or use statistical methods accounting for pretreatment morbidity when relevant.