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Short-course versus long-course neoadjuvant radiotherapy for lower rectal cancer: a systematic review |
Sajid MS, Siddiqui MR, Kianifard B, Baig MK |
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CRD summary The review found no evidence of a difference between neoadjuvant short-course radiotherapy and long-course radiotherapy/chemoradiation in survival, recurrence, complications, sphincter preservation and toxicity in lower rectal cancer patients. The authors’ conclusions reflected the evidence base but, given shortcomings in the review process, and variation and poor quality of the included trials, the conclusions should be considered tentative. Authors' objectives To assess the efficacy of short-course versus long-course radiotherapy as neoadjuvant therapy for the management of lower rectal cancer. Searching PubMed, EMBASE, CINAHL and the Cochrane Library were searched, with no language restrictions, for relevant studies published between January 1980 and August 2008; search terms were reported. The related article function was also used to find additional studies. Study selection Eligible studies were randomised controlled trials (RCTs) that compared the efficacy of short-course and long-course radiotherapy or chemoradiotherapy as neoadjuvant modality for lower rectal cancer in patients of any age or sex. Eligible outcomes were overall survival, recurrence, time to recurrence, response rate, radiotherapy related toxicity, perioperative complications and sphincter preservation. Participants in the included trials had either T2 to T4 tumours (with nodal status 0 to 2 and without metastases) or T3 to T4 tumours. Short-course radiotherapy was 5x5Gy given for five days or one week, followed by surgery within five days or one week. Long-course radiotherapy/chemoradiotherapy was either 2Gy per fraction for five weeks, or 1.8Gy per fraction for 5.5 weeks plus two courses of chemotherapy with 5-fluorouracil and leucovorin, followed by surgery four to six weeks later. Two reviewers undertook study selection, but it was not reported how disagreements were resolved. Assessment of study quality Trials were assessed for quality. Criteria included explicit statement of inclusion and exclusion criteria, randomisation technique, sample size calculation, baseline comparability, blinding, cross-over, completeness of follow-up, allocation concealment, and intention-to-treat analysis. It appeared that two reviewers undertook quality assessment, but it was not reported how disagreements were resolved. Data extraction Risk ratios (RRs) and odds ratios (ORs) were extracted, with their 95% confidence intervals (CIs), for the planned dichotomous outcomes. The authors did not report how they planned to extract continuous data for time to recurrence. Authors were contacted for missing data (where necessary). Two reviewers extracted data separately, which were confirmed by a third reviewer. Methods of synthesis Trials were pooled in meta-analyses and summary risk ratios and odds ratios, and their 95% confidence intervals, were calculated using both a Mantel Haenszel fixed-effect model and a DerSimonian and Laird random-effects model. The X2 test was used to assess whether the fixed-effect model was appropriate. Sensitivity analyses were undertaken by adding 0.5 to each cell frequency for trials where no events occurred in either the short-course or long-course radiotherapy group. Results of the review Two RCTs were included in the review (n=396 patients). Neither trial reported blinding or allocation concealment. One trial reported intention-to-treat analysis. Duration of follow-up was one month in one trial and ranged from 22 to 84 months in the other trial. There was no evidence of a significant difference in either overall survival or rate of recurrence of lower rectal cancer between short-course and long-course radiotherapy groups for overall survival (OR 0.99, 95% CI 0.97 to 1.01; fixed-effect model) or cancer recurrence (RR 1.41, 95% CI 0.25 to 7.80; fixed-effect model). There was no evidence of a significant difference in the rate of perioperative complications after surgery or rate of sphincter preservation between the therapy groups for complications (RR 0.77, 95% CI 0.51 to 1.16; fixed-effect model) or sphincter preservation (OR 0.89, 95% CI 0.75 to 1.07; fixed-effect model). There was also no evidence of significant heterogeneity in any of these analyses. There was significantly lower radiotherapy-related toxicity with long-course radiotherapy compared with short-course radiotherapy using a fixed-effect model (RR 2.49, 95% CI 2.01 to 3.10), but not using a random-effects model (RR 1.89, 95% CI 0.54 to 6.59); there was significant heterogeneity between trials. There were insufficient data to analyse response rate or time to recurrence. Authors' conclusions Short-course radiotherapy as neoadjuvant therapy in the management of lower rectal cancer may be as effective as traditional long-course radiotherapy for overall survival, disease recurrence, perioperative complications, sphincter preservation and toxicity. CRD commentary The review addressed a clear research question and inclusion criteria appear specific and appropriate. A number of databases were searched for relevant studies using appropriate search terms and without language restriction. No attempts were made to find unpublished studies and there was no formal assessment of the likelihood of publication bias, so publication bias could not be ruled out. Appropriate methods (designed to reduce reviewer bias and error) were used to select studies, undertake quality assessment of included studies and perform data extraction. Details on trial quality were appropriately assessed and reported in tables. Lack of blinding and allocation concealment in the included trials may have had an effect on outcome assessment, so bias could not be ruled out. Variation in the duration of follow up, staging of tumours and measurement criteria of the tumour between trials and lack of control of the confounding variable of adjuvant chemotherapy may have influenced results, but there was no evidence of significant heterogeneity for most outcomes. Some of the summary estimates were expressed as odds ratios and others as risk ratios; the rationale for selecting one or the other method was not reported. Subgroup and sensitivity analyses were not feasible due to the limited number of trials. The authors’ conclusions reflected the evidence base, but given shortcomings in the review process, and variation and poor quality of the included trials, these conclusions should be considered tentative. Implications of the review for practice and research Practice: The authors stated that traditional neoadjuvant chemoradiation may continue to be used for patients with lower rectal cancer. Research: The authors stated that a major multicenter RCT was required to further assess the benefits and harms of short-course or long-course radiotherapy. Bibliographic details Sajid MS, Siddiqui MR, Kianifard B, Baig MK. Short-course versus long-course neoadjuvant radiotherapy for lower rectal cancer: a systematic review. Irish Journal of Medical Science 2010; 179(2): 165-171 Indexing Status Subject indexing assigned by NLM MeSH Confidence Intervals; Great Britain; Humans; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Odds Ratio; Preoperative Care; Radiotherapy, Adjuvant; Rectal Neoplasms /drug therapy /mortality /radiotherapy; Risk; Time Factors; Treatment Outcome AccessionNumber 12010005320 Date bibliographic record published 15/09/2010 Date abstract record published 23/02/2011 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
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