Abstract: We studied 8228 women in nine studies. Eight out of nine studies were at low or unclear risk of bias. Altered fraction size (delivering radiation therapy in larger amounts each day but over fewer days than with conventional fractionation) did not have a clinically meaningful effect on: local recurrence-free survival (Hazard Ratio (HR) 0.94, 95% CI 0.77 to 1.15, 7095 women, four studies, high-quality evidence), cosmetic outcome (Risk ratio (RR) 0.90, 95% CI 0.81 to 1.01, 2103 women, four studies, high-quality evidence) or overall survival (HR 0.91, 95% CI 0.80 to 1.03, 5685 women, three studies, high-quality evidence). Acute radiation skin toxicity (RR 0.32, 95% CI 0.22 to 0.45, 357 women, two studies) was reduced with altered fraction size. Late radiation subcutaneous toxicity did not differ with altered fraction size (RR 0.93, 95% CI 0.83 to 1.05, 5130 women, four studies, high-quality evidence). Breast cancer-specific survival (HR 0.91, 95% CI 0.78 to 1.06, 5685 women, three studies, high quality evidence) and relapse-free survival (HR 0.93, 95% CI 0.82 to 1.05, 5685 women, three studies, moderate-quality evidence) did not differ with altered fraction size. We found no data for mastectomy rate. Altered fraction size was associated with less patient-reported (P < 0.001) and physician-reported (P = 0.009) fatigue at six months (287 women, one study). We found no difference in the issue of altered fractionation for patient-reported outcomes of: physical well-being (P = 0.46), functional well-being (P = 0.38), emotional well-being (P = 0.58), social well-being (P = 0.32), breast cancer concerns (P = 0.94; 287 women, one study). We found no data with respect to costs. We found that using altered fraction size regimens (greater than 2 Gy per fraction) does not have a clinically meaningful effect on local recurrence, is associated with decreased acute toxicity and does not seem to affect breast appearance, late toxicity or patient-reported quality-of-life measures for selected women treated with breast conserving therapy. These are mostly women with node negative tumours smaller than 3 cm and negative pathological margins.

Plain-language summary: Nine studies, involving 8228 women, were included in this review. Most of the women in the studies (91%) had tumours 3 cm or less in size, all had complete removal of the tumour on pathology and 68% had no evidence of cancer in their lymph nodes. Where the breast size was known, 83% had small or medium breasts. The evidence is current up to May 2015. Local recurrence was not different for women having fewer treatments (four fewer local relapses per 1000 (where the true value may be anywhere between 16 fewer to 10 more local relapses per 1000)). Breast appearance was not different for women undergoing fewer treatments (31 fewer fair/poor breast appearance per 1000 (where the true value may be anywhere between 59 fewer to 3 more per 1000 with fair/poor breast appearance)). Survival was not altered by having fewer treatments (13 fewer deaths per 1000 (where the true value could be between 31 fewer to 5 more deaths per 1000)) and there was no significant difference in late skin toxicity (4 more episodes of toxicity per 1000; where the true value may be anywhere between 14 fewer to 36 more episodes of toxicity per 1000) or radiation toxicity. Acute skin toxicity is decreased with fewer treatments (326 fewer events per 1000 (where the true value may be anywhere between 264 fewer to 374 fewer acute skin toxicity events per 1000)). This review indicates that for women who fit these criteria, using fewer radiation treatments after tumour removal gives the same cancer control, with less skin reaction at the time and the likely the same side-effects in the long term. We found high quality evidence for the following outcomes: local recurrence-free survival, breast appearance, toxicity, overall survival and breast cancer-specific survival. We found moderate quality evidence for relapse-free survival, and no data for mastectomy rate (mastectomy may be required because of local recurrence or unacceptable treatment-related toxicity) or costs.