Adjuvant Breast Radiation Therapy for Early-Stage Breast Cancer or Ductal Carcinoma In-Situ in the Breast: A Systematic Review and Network Meta-Analysis of Randomized Trials

For selected patients with early-stage breast cancer (BC) or ductal carcinoma in-situ (DCIS) in the breast, adjuvant breast radiation therapy (RT) approaches include partial breast irradiation (PBI), altered fractionation (AF) whole breast irradiation (WBI) or tumor bed boost (TBB). However, it is unclear which is the optimal approach. This study aims to compare the effects of different PBI, AF-WBI and TBB options on ipsilateral breast tumor recurrence (IBTR), overall survival (OS) and patient reported cosmesis (PRC) outcomes.We searched various biomedical electronic databases for eligible randomized trials (RCTs) from date of inception to January 2023. We constructed six separate random effects frequentist network meta-analyses (NMA) to compare the effects of various PBI options using WBI as the reference; various AF-WBI options using conventional fractionated (CF) WBI as the reference and various TBB options using no TBB as the reference on IBTR and OS. The GRADE approach was used to assess the certainty of evidence. The synthesis without meta-analysis approach was pre-specified for evaluation of PRC in anticipation of various assessment and reporting methods.We included 34 RCTs comprising 49,899 participants and 11 treatment options. Evidence suggests that accelerated PBI (Hazard Ratio (HR) 1.36 (95% confidence interval (CI) 0.77 - 2.41, moderate certainty), moderately hypofractionated (MHF) PBI (HR 1.38 (0.60 - 3.19), moderate certainty) and intraoperative PBI (HR 1.47 (0.81 - 2.68), low certainty) was associated with a modest but not statistically significant increase in the hazards for IBTR when compared to WBI. There was moderate certainty evidence that there were no significant differences among the accelerated ultra-hypo fractionated (AUHF) WBI (HR 0.76 (0.50 - 1.14)), MHF-WBI (HR 0.99 (0.84 - 1.16)) or UHF-WBI (HR (1.35 (0.47 - 3.92)) when compared with CF-WBI for IBTR. The effects of sequential TBB (seqTBB) (HR 0.61 (0.52 - 0.70), high certainty) and simultaneous integrated TBB (simTBB) (HR 0.77 (0.55 - 1.09), moderate certainty) on IBTR were similar when compared to no TBB. There were no significant differences in OS between PBI options and WBI, AF-WBI options and CF-WBI, TBB options and no TBB. Among the PBI vs WBI trials, MHF-PBI and APBI may be associated with fewer adverse PRC events. Among the AF-WBI vs CF-WBI trials, half of the included trials reported fewer adverse PRC events with MHF-WBI. SeqTBB and simTBB had similar adverse PRC outcome.There were no significant differences among the PBI, AF-WBI and TBB options for IBTR and OS. PBI and AF-WBI may be associated with less adverse PRC events compared with WBI and CF-WBI respectively. There was no evidence to suggest a difference between seqTBB and simTBB for PRC outcome. This study is registered with PROSPERO CRD 42021245074.