Isabelle Kindts, Annouschka Laenen, Tom Depuydt, Caroline Weltens

Breast-conserving therapy, involving breast-conserving surgery followed by whole-breast irradiation and optionally a boost to the tumour bed, is a standard therapeutic option for women with early-stage breast cancer. A boost to the tumour bed means that an extra dose of radiation is applied that covers the initial tumour site. The rationale for a boost of radiotherapy to the tumour bed is that (i) local recurrence occurs mostly at the site of the primary tumour because remaining microscopic tumour cells are most likely situated there; and (ii) radiation can eliminate these causative microscopic tumour cells. The boost continues to be used in women at high risk of local recurrence, but is less widely accepted for women at lower risk. Reasons for questioning the boost are twofold. Firstly, the boost brings higher treatment costs. Secondly, the potential adverse events are not negligible. In this Cochrane Review, we investigated the effect of the tumour bed boost on local control and side effects. To assess the effects of tumour bed boost radiotherapy after breast-conserving surgery and whole-breast irradiation for the treatment of breast cancer. We searched the Cochrane Breast Cancer Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (January 1966 to 1 March 2017), Embase (1980 to 1 March 2017), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov on 1 March 2017. We also searched the European Society of Radiotherapy and Oncology Annual Meeting, the St Gallen Oncology Conferences, and the American Society for Radiation Oncology Annual Meeting for abstracts. Randomised controlled trials comparing the addition and the omission of breast cancer tumour bed boost radiotherapy. Two review authors (IK and CW) performed data extraction and assessed risk of bias using Cochrane's 'Risk of bias' tool, resolving any disagreements through discussion. We entered data into Review Manager 5 for analysis and applied GRADE to assess the quality of the evidence. We included 5 randomised controlled trials analysing a total of 8325 women.Local control appeared to be better for women receiving a tumour bed boost compared to no tumour bed boost (hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.55 to 0.75; 5 studies, 8315 women, low-quality evidence). Overall survival did not differ with or without a tumour bed boost (HR 1.04, 95% CI 0.94 to 1.14; 2 studies, 6342 women, moderate-quality evidence). Disease-free survival did not differ with or without a tumour bed boost (HR 0.94, 95% CI 0.87 to 1.02; 3 studies, 6549 women, low-quality evidence). Late toxicity scored by means of percentage of breast retraction assessment did not differ with or without a tumour bed boost (mean difference 0.38, 95% CI -0.18 to 0.93; 2 studies, 1526 women, very low-quality evidence). Cosmesis scored by a panel was better (i.e. excellent or good compared to fair or poor) in the no-boost group (odds ratio (OR) 1.41, 95% CI 1.07 to 1.85; 2 studies, 1116 women, low-quality evidence). Cosmesis scored by a physician did not differ with or without a tumour bed boost (OR 1.58, 95% CI 0.93 to 2.69; 2 studies, 592 women, very low-quality evidence).We excluded two studies in a sensitivity analysis of local recurrence (because the biological equivalent dose (BED) to the tumour bed was lower, in situ tumours were included, or there was a high risk of selective reporting bias or blinding of outcome assessment bias), which resulted in a HR of 0.62 (95% CI 0.52 to 0.73; 3 studies, 6963 women, high-quality evidence). Subgroup analysis including women older than 40 years of age yielded a HR of 0.65 (95% CI 0.53 to 0.81; 2 studies, 5058 women, high-quality evidence).We found no data for the outcomes of acute toxicity, quality of life, or costs. It appears that local control rates are increased with the boost to the tumour bed, but we found no evidence of a benefit for other oncological outcomes. Subgroup analysis including women older than 40 years of age yielded similarly significant results. Objective percentage of breast retraction assessment appears similar between groups. It appears that the cosmetic outcome is worse with the boost to the tumour bed, but only when measured by a panel, not when assessed by a physician.