Kristopher Dennis1, Rehana Jamani2, Clare McGrath3, Leila Makhani4, Henry Lam5, Patrick Bauer6, Carlo De Angelis7, Natalie Coburn8, C Shun Wong9, Edward Chow9. 1. Division of Radiation Oncology, The Ottawa Hospital and the University of Ottawa, 501 Smyth Rd, Ottawa, Ontario, K1H 8L6, Canada. krdennis@toh.ca. 2. Queen's University, Kingston, Ontario, Canada. 3. Division of Radiation Oncology, The Ottawa Hospital and the University of Ottawa, 501 Smyth Rd, Ottawa, Ontario, K1H 8L6, Canada. 4. Department of Family and Community Medicine, Global Health and Vulnerable Populations, University of Toronto, Toronto, Ontario, Canada. 5. Sunnybrook R. Ian Macdonald Library, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. 6. Jagiellonian University Medical College, Krakow, Poland. 7. Department of Pharmacy, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. 8. Division of General Surgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. 9. Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
Abstract
PURPOSE: Clinical trials in radiation therapy-induced nausea and vomiting (RINV) appear to have varied methodologies, endpoints, and outcome measures. This complicates trial comparisons, weakens practice guideline recommendations, and contributes to variability in supportive care patterns of practice. We systematically reviewed RINV trials to describe and compare their pertinent design features. MATERIALS AND METHODS: Ovid versions of the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, EMBASE, and MEDLINE to January/February 2017 were searched for adult phase III trials of RINV management strategies. Key abstracted data included trial interventions and eligibility criteria, standard radiation therapy (RT) metrics, symptom assessment procedures, symptom definitions and grading systems, pre-specified and reported endpoints, and other outcome measures. RESULTS: From 1166 references identified in the initial database search, we selected 34 trials for analysis that collectively randomized 4529 patients (median 61, range 11-1492). Twenty-eight trials (82%) were published prior to the year 2000. Twenty-seven trials (79%) involved multiple fraction RT and 7 (21%) single fraction RT. Twenty-four trials (71%) evaluated prophylactic interventions, 9 (26%) rescue interventions, and 1 trial did not specify. Thirty-three trials (97%) evaluated pharmacologic interventions. Twenty trials (59%) had patient report symptoms, 5 (15%) healthcare professionals or researchers, and 10 (29%) did not specify. Nausea was not defined in any trial but was reported as a stand-alone symptom in 26 trials (76%) and was graded in 20 (59%), with categorical qualitative scales being the most common method. Vomiting was defined in 3 trials (9%), was reported as a stand-alone symptom in 17 (47%), and was graded in 7 (21%), with continuous numerical scales being the most common method. Retching was defined in 3 trials, was not reported as a stand-alone symptom in any trial, and was graded in 1 (3%). Twenty-one trials (62%) created compound symptom measures that combined individual symptoms. Fifteen trials (44%) reported "emetic episode/event" measures but only 9 defined them. Seventeen trials (50%) reported complicated endpoints (e.g., "response," "control," "success") that combined multiple symptom or compound symptom measures, but 7 did not define them comprehensively. Ten trials (29%) defined a primary endpoint a priori. CONCLUSIONS: Methodologies, endpoints, and outcome measures varied considerably among 34 randomized trials in RINV.
PURPOSE: Clinical trials in radiation therapy-induced nausea and vomiting (RINV) appear to have varied methodologies, endpoints, and outcome measures. This complicates trial comparisons, weakens practice guideline recommendations, and contributes to variability in supportive care patterns of practice. We systematically reviewed RINV trials to describe and compare their pertinent design features. MATERIALS AND METHODS: Ovid versions of the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, EMBASE, and MEDLINE to January/February 2017 were searched for adult phase III trials of RINV management strategies. Key abstracted data included trial interventions and eligibility criteria, standard radiation therapy (RT) metrics, symptom assessment procedures, symptom definitions and grading systems, pre-specified and reported endpoints, and other outcome measures. RESULTS: From 1166 references identified in the initial database search, we selected 34 trials for analysis that collectively randomized 4529 patients (median 61, range 11-1492). Twenty-eight trials (82%) were published prior to the year 2000. Twenty-seven trials (79%) involved multiple fraction RT and 7 (21%) single fraction RT. Twenty-four trials (71%) evaluated prophylactic interventions, 9 (26%) rescue interventions, and 1 trial did not specify. Thirty-three trials (97%) evaluated pharmacologic interventions. Twenty trials (59%) had patient report symptoms, 5 (15%) healthcare professionals or researchers, and 10 (29%) did not specify. Nausea was not defined in any trial but was reported as a stand-alone symptom in 26 trials (76%) and was graded in 20 (59%), with categorical qualitative scales being the most common method. Vomiting was defined in 3 trials (9%), was reported as a stand-alone symptom in 17 (47%), and was graded in 7 (21%), with continuous numerical scales being the most common method. Retching was defined in 3 trials, was not reported as a stand-alone symptom in any trial, and was graded in 1 (3%). Twenty-one trials (62%) created compound symptom measures that combined individual symptoms. Fifteen trials (44%) reported "emetic episode/event" measures but only 9 defined them. Seventeen trials (50%) reported complicated endpoints (e.g., "response," "control," "success") that combined multiple symptom or compound symptom measures, but 7 did not define them comprehensively. Ten trials (29%) defined a primary endpoint a priori. CONCLUSIONS: Methodologies, endpoints, and outcome measures varied considerably among 34 randomized trials in RINV.
Authors: Kristopher Dennis; Liying Zhang; Stephen Lutz; Angela van Baardwijk; Yvette van der Linden; Tanya Holt; Palmira Foro Arnalot; Jean-Léon Lagrange; Ernesto Maranzano; Rico Liu; Kam-Hung Wong; Lea-Choung Wong; Vassilios Vassiliou; Benjamin W Corn; Carlo De Angelis; Lori Holden; C Shun Wong; Edward Chow Journal: Int J Radiat Oncol Biol Phys Date: 2012-06-15 Impact factor: 7.038
Authors: Y Belkacémi; M Ozsahin; F Pène; B Rio; L Sutton; J P Laporte; E Touboul; N C Gorin; A Laugier Journal: Int J Radiat Oncol Biol Phys Date: 1996-08-01 Impact factor: 7.038
Authors: R Miralbell; P Coucke; F Behrouz; N Blazek; M Melliger; S Philipp; R Wickenhauser; S Gebhard; T Schwabb; A Rosset Journal: Eur J Cancer Date: 1995 Impact factor: 9.162