title: Systematic Review of Radiation Therapy Toxicity Reporting in Randomized Controlled Trials of Rectal Cancer: A Comparison of Patient-Reported Outcomes and Clinician Toxicity Reporting.
abstract: The use of multimodal treatments for rectal cancer has improved cancer-related outcomes but makes monitoring toxicity challenging. Optimizing future radiation therapy regimens requires collection and publication of detailed toxicity data. This review evaluated the quality of toxicity information provided in randomized controlled trials (RCTs) of radiation therapy in rectal cancer and focused on the difference between clinician-reported and patient-reported toxicity. Medline, EMBASE, and the Cochrane Library were searched (January 1995-July 2013) for RCTs reporting late toxicity in patients treated with regimens including preoperative (chemo)radiation therapy. Data on toxicity measures and information on toxicity reported were extracted using Quantitative Analyses of Normal Tissue Effects in the Clinic recommendations. International Society for Quality of Life Research standards on patient-reported outcomes (PROs) were used to evaluate the quality of patient-reported toxicity. Twenty-one RCT publications met inclusion criteria out of 4144 articles screened. All PRO studies reported higher rates of toxicity symptoms than clinician-reported studies and reported on a wider range and milder symptoms. No clinician-reported study published data on sexual dysfunction. Of the clinician-reported studies, 55% grouped toxicity data related to an organ system together (eg "Bowel"), and 45% presented data only on more-severe (grade ≥3) toxicity. In comparison, all toxicity grades were reported in 79% of PRO publications, and all studies (100%) presented individual symptom toxicity data (eg bowel urgency). However, PRO reporting quality was variable. Only 43% of PRO studies presented baseline data, 28% did not use any psychometrically validated instruments, and only 29% of studies described statistical methods for managing missing data. Analysis of these trials highlights the lack of reporting standards for adverse events and reveals the differences between clinician and patient reporting of toxicity. Recommendations for improving the quality of adverse event data collection are provided, with the aim of improving critical appraisal of outcomes for future studies.
authors.affiliation: Leeds Institute of Cancer & Pathology, University of Leeds, Leeds, United Kingdom. Electronic address: a.gilbert@leeds.ac.uk.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gilbert
authors.affiliation: Leeds Institute of Cancer & Pathology, University of Leeds, Leeds, United Kingdom.
authors.forename: Lucy
authors.initials: L
authors.lastname: Ziegler
authors.affiliation: Leeds Institute of Cancer & Pathology, University of Leeds, Leeds, United Kingdom.
authors.forename: Maisie
authors.initials: M
authors.lastname: Martland
authors.affiliation: The Christie Hospital, Manchester, United Kingdom.
authors.forename: Susan
authors.initials: S
authors.lastname: Davidson
authors.affiliation: Italian Group for Adult Hematologic Diseases, Rome, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Efficace
authors.affiliation: Leeds Institute of Cancer & Pathology, University of Leeds, Leeds, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Sebag-Montefiore
authors.affiliation: Leeds Institute of Cancer & Pathology, University of Leeds, Leeds, United Kingdom.
authors.forename: Galina
authors.initials: G
authors.lastname: Velikova
mesh_terms: D000465:Algorithms; D059248:Chemoradiotherapy; D003625:Data Collection / Q000592:standards; D004414:Dyspareunia / Q000453:epidemiology; D007172:Erectile Dysfunction / Q000453:epidemiology; D005242:Fecal Incontinence / Q000453:epidemiology; D005260:Female; D006801:Humans; D007422:Intestines / Q000528:radiation effects; D008297:Male; D058958:Organs at Risk / Q000528:radiation effects*; D063868:Patient Outcome Assessment; D011643:Publishing / Q000592:standards*; D058996:Quality Improvement; D011788:Quality of Life; D011832:Radiation Injuries / Q000453:epidemiology*; D018787:Radiation Oncology / Q000706:statistics & numerical data; D016032:Randomized Controlled Trials as Topic; D012004:Rectal Neoplasms / Q000532:radiotherapy*; D014549:Urinary Incontinence / Q000453:epidemiology