Objective To 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. Design Systematic review and meta-analysis. Data sources Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (from inception to 23 October 2023). Study selection Included 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 extraction Two 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 synthesis Pooled 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 measures The 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. Results From 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<0.001) and 0.68 (0.49 to 0.93; P=0.02) following breast conserving therapy and mastectomy, respectively. Hyperpigmentation and grade ≥2 breast shrinkage were less frequent after MHF than after CF, with RRs of 0.77 (0.62 to 0.95; P=0.02) and 0.92 (0.85 to 0.99; P=0.03), respectively, in the combined breast conserving therapy and mastectomy population. However, in the breast conserving therapy only trials, these differences in hyperpigmentation (RR 0.79, 0.60 to 1.03; P=0.08) and breast shrinkage (0.94, 0.83 to 1.07; P=0.35) were not statistically significant. The RR for grade ≥2 acute radiation dermatitis for UHF compared with MHF was 0.85 (0.47 to 1.55; P=0.60) for breast conserving therapy and mastectomy patients combined. MHF was associated with improved cosmesis and quality of life compared with CF, whereas data on UHF were less conclusive. Survival and recurrence outcomes were similar between UHF, MHF, and CF. Conclusions MHF shows improved safety profile, cosmesis, and quality of life compared with CF while maintaining equivalent oncological outcomes. Fewer randomised controlled trials have compared UHF with other fractionation schedules, but its safety and oncological effectiveness seem to be similar with short term follow-up. Given the advantages of reduced treatment time, enhanced convenience for patients, and potential cost effectiveness, MHF and UHF should be considered as preferred options over CF in appropriate clinical settings, with further research needed to solidify these findings. Systematic review registration PROSPERO CRD42023460249. Data analysed were based on published data. Template data forms, the data extracted from included studies, and data used for analyses are available from the corresponding author on reasonable request. The study protocol is published on PROSPERO (ID: CRD42023460249)

中文翻译：

---

乳腺癌辐射剂量分割的随机对照试验：系统评价和荟萃分析，重点关注副作用和美容


目的 对乳腺癌放射治疗的各种分割方案进行综合评估，重点关注副作用、美观、生活质量、复发风险和生存结果。设计系统回顾和荟萃分析。数据来源 Ovid MEDLINE、Embase 和 Cochrane 对照试验中央注册库（从开始到 2023 年 10 月 23 日）。研究选择 纳入的研究为随机对照试验，重点关注传统分割（CF；每日分割 1.8-2 Gy，5-6 周内达到总剂量 50-50.4 Gy）、中度大分割（MHF；分割大小 2.65-3.3） Gy（3-5 周内 13-16 次分割）和/或超低分割（UHF；仅 5 次分割的时间表）。数据提取 两名独立研究者筛选研究并提取数据。偏倚风险和证据质量分别使用 Cochrane 协作组织的工具和 GRADE（建议、评估、制定和评价分级）方法进行评估。数据合成 使用随机效应模型计算具有 95% 置信区间 (CI) 的合并风险比 (RR) 和危险比 (HR)。使用 Cochran's Q 检验和 I2 统计分析异质性。使用网络荟萃分析来整合所有可用的证据。主要结局指标 预先指定的主要结局是≥2级急性放射性皮炎和晚期放射治疗相关副作用；次要结局包括美容、生活质量、复发和生存指标。结果 对 1754 项研究中代表 35 项试验（20 237 名患者）的 59 篇文章进行了评估； 21.6% 的结果显示偏倚风险较低，而 78.4% 的结果存在一些担忧或高风险，特别是在结果测量方面 (47.4%)。 与 CF 相比，保乳治疗和乳房切除术后发生 ≥2 级急性放射性皮炎的 RR 分别为 0.54（95% CI 0.49 至 0.61；P<0.001）和 0.68（0.49 至 0.93；P=0.02）。 MHF 后色素沉着过度和≥2 级乳房萎缩的发生率低于 CF 后，在联合保乳治疗和联合保乳治疗中，RR 分别为 0.77（0.62 至 0.95；P=0.02）和 0.92（0.85 至 0.99；P=0.03）。乳房切除术人群。然而，在仅进行保乳治疗的试验中，色素沉着过度（RR 0.79，0.60至1.03；P=0.08）和乳房萎缩（0.94，0.83至1.07；P=0.35）的差异没有统计学意义。与 MHF 相比，保乳治疗和乳房切除术患者发生 ≥2 级急性放射性皮炎的 RR 为 0.85（0.47 至 1.55；P=0.60）。与 CF 相比，MHF 与改善美观和生活质量相关，而 UHF 的数据则不太确定。 UHF、MHF 和 CF 之间的生存和复发结果相似。结论 与 CF 相比，MHF 的安全性、美观性和生活质量得到改善，同时保持相同的肿瘤学结果。将 UHF 与其他分割方案进行比较的随机对照试验较少，但其安全性和肿瘤学有效性似乎与短期随访相似。鉴于减少治疗时间、提高患者便利性以及潜在成本效益等优点，在适当的临床环境中，MHF 和 UHF 应被视为优于 CF 的首选方案，需要进一步研究来巩固这些发现。系统审评注册PROSPERO CRD42023460249。分析的数据基于已发布的数据。 模板数据表格、从纳入的研究中提取的数据以及用于分析的数据可根据合理要求从通讯作者处获得。研究方案发布在 PROSPERO 上（ID：CRD42023460249）