Randomised controlled trials on radiation dose fractionation in breast cancer: systematic review and meta-analysis with emphasis on side effects and cosmesis

• Published in: BMJ (Online) 2024-09, Vol.386, p.e079089
• Main Authors: Lee, Shing Fung, Kennedy, Samantha K F, Caini, Saverio, Wong, Henry C Y, Yip, Pui Lam, Poortmans, Philip M, Meattini, Icro, Kaidar-Person, Orit, Recht, Abram, Hijal, Tarek, Torres, Mylin A, Cao, Jeffrey Q, Corbin, Kimberly S, Choi, J Isabelle, Koh, Wee Yao, Kwan, Jennifer Y Y, Karam, Irene, Chan, Adrian W, Chow, Edward, Marta, Gustavo N
• Format: Article
• Language: English
• Subjects: Bias; Breast cancer; Breast Neoplasms - radiotherapy; Cancer therapies; Clinical trials; Dermatitis; Dose Fractionation, Radiation; Dosimetry; Female; Fractionation; Humans; Hyperpigmentation; Mastectomy; Meta-analysis; Neoplasm Recurrence, Local; Patients; Quality of Life; Radiation measurement; Radiation therapy; Randomized Controlled Trials as Topic; Reimbursement; Side effects; Statistical analysis; Survival; Systematic review
• ISSN: 1756-1833; 1756-1833
• DOI: 10.1136/bmj-2023-079089

AbstractObjectiveTo provide a comprehensive assessment of various fractionation schemes in radiation therapy for breast cancer, with a focus on side effects, cosmesis, quality of life, risks of recurrence, and survival outcomes.DesignSystematic review and meta-analysis.Data sourcesOvid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (from inception to 23 October 2023).Study selectionIncluded studies were randomised controlled trials focusing on conventional fractionation (CF; daily fractions of 1.8-2 Gy, reaching a total dose of 50-50.4 Gy over 5-6 weeks), moderate hypofractionation (MHF; fraction sizes of 2.65-3.3 Gy for 13-16 fractions over 3-5 weeks), and/or ultra-hypofractionation (UHF; schedule of only 5 fractions).Data extractionTwo independent investigators screened studies and extracted data. Risk of bias and quality of evidence were assessed using the Cochrane Collaboration’s tool and the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach, respectively.Data synthesisPooled risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random effects model. Heterogeneity was analysed using Cochran’s Q test and I2 statistic. Network meta-analysis was used to integrate all available evidence.Main outcome measuresThe pre-specified primary outcome was grade ≥2 acute radiation dermatitis and late radiation therapy related side effects; secondary outcomes included cosmesis, quality of life, recurrence, and survival metrics.ResultsFrom 1754 studies, 59 articles representing 35 trials (20 237 patients) were assessed; 21.6% of outcomes showed low risk of bias, whereas 78.4% had some concerns or high risk, particularly in outcome measurement (47.4%). The RR for grade ≥2 acute radiation dermatitis for MHF compared with CF was 0.54 (95% CI 0.49 to 0.61; P