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This randomized trial of fractionation after breast reconstruction (FABREC) sought to compare quality-of-life (QOL) and clinical outcomes of hypofractionated (HF) vs. conventionally-fractionated (CF) postmastectomy radiation therapy (PMRT) in the setting of immediate prosthetic reconstruction. Between 3/2018 and 11/2021, 400 patients at 18 centers with Stage 0-III breast cancer and immediate placement of tissue expander (TE) or implant (I) after mastectomy were randomized 1:1 to HF or CF photon PMRT. Respective doses in the two arms were 42.56 Gy/16 fractions to the chest wall (CW), with or without axillary/supraclavicular lymph node (LN) radiation (39.9 Gy/15 fractions) and 50 Gy in 25 fractions to CW (46-50 Gy to axillary LNs). A boost was not permitted; bolus was used at physician discretion. CW toxicity was defined as any grade ≥3 adverse event (CTCAE) after PMRT initiation. Patients were censored at study withdrawal or at diagnosis of distant recurrence. Participants completed QOL instruments (FACT-B, BREAST-Q, Lymph-ICF) at baseline, 6, 12 and 18-months from PMRT initiation. Questions regarding financial burden were included with the 6-month survey. Primary endpoint of the study was improvement in the Physical Well-Being (PWB) domain of FACT-B at 6 months with pre-specified stratification by age (younger than 45 vs. 45 years or older). QOL scores were compared using Student's t-test. Median follow-up for the 385 patients analyzed was 31.8 months (range, 6.9-54.4); median age was 47.0 years (range, 23-79). Preoperative chemotherapy was used in 67.8% and preoperative endocrine therapy (ET) in 21.5% of the cohort. There were 16 distant (8 in each arm), and 2 local-regional (1 in each arm) recurrences. CW toxicity occurred in 35 patients (19 HF, 16 CF, p=0.58) at medians of 3.4 and 4.8 months after RT initiation in the HF and CF arms, respectively (p=0.82). Post-operative infection before RT (HR=3.31, p=0.03), irradiation of TE vs I (HR=7.74, p=0.046), preoperative endocrine therapy (HR=3.45, p=0.0007) and number of LNs removed (HR=1.06/node, p=0.02) were significant for developing CW toxicity on multivariate analysis, while fractionation was not (HF HR=1.19, p=0.63). There was no significant difference in overall change in PWB scores at 6 months between the two treatment arms (p=0.71) or separately in younger (p=0.15) and older cohorts (p=0.27). However, HF patients younger than 45 were less bothered by side-effects of treatment (p=0.045) and nausea (p=0.02) vs. CF patients younger than 45. Among patients who took unpaid time off from work during treatment (n=51), those receiving HF required fewer hours off than those receiving CF (73.7 vs. 125.8, p=0.046). Physical well-being and overall toxicity profile of HF PMRT were comparable between HF and CF PMRT. HF was associated with better 6-month QOL in some domains among younger patients. Our early results support the use of HF PMRT in the setting of TE- or implant-based breast reconstruction. [ABSTRACT FROM AUTHOR]

Post-mastectomy radiotherapy (PMRT) is associated with increased risk of implant-based breast reconstruction complications. We sought to examine the relationship between clinical/dosimetric factors and implant reconstruction complications. We conducted a retrospective study of breast cancer patients (pts) who underwent simulation for PMRT from 2012 to 2015 following single-stage or two-stage implant-based reconstruction. Demographic, disease, treatment, and reconstruction outcomes data were collected. Major reconstruction complication (MRC) was defined as any complication requiring unplanned reoperation or removal. Clinical/dosimetric factors associated with MRC were determined by Cox regression. Cutpoints for dosimetric variables were determined by the Contal and O'Quigley method. We identified 111 pts who underwent PMRT following implant-based reconstruction. 91% underwent two-stage reconstruction with PMRT to a tissue expander (TE) and 9% underwent single-stage reconstruction with PMRT to the permanent implant (PI). All pts were treated using 3D-CRT with conventional fractionation (1.8-2 Gy/day) for the majority of their treatment. 11 pts (10%) received hypofractionated (2.1-3 Gy) treatment for the last 2-5 fractions for scheduling reasons and were excluded from dosimetric analysis. 44% received a chest wall boost (4-10 Gy). At a median follow-up of 6.6 years, 45 pts (41%) experienced an MRC (8 had MRC while TE was in place, 7%; 37 had MRC while PI was in place, 33%). Following MRC, at time of last follow-up/death, 15 pts lacked replacement reconstruction and 12 had autologous reconstruction. Median time from end of PMRT to MRC was 1.6 yrs. The most common types of MRC were contracture (31%), infection (22%), asymmetry (18%), and threatened exposure of the PI (7%). On univariate analysis, there was no significant difference between pts with or without MRC with respect to age, race, smoking history, menopause status, chemotherapy or hormonal therapy, or reconstruction timing. Obesity (P = 0.03; HR 2.26, 1.08-4.76) and infection occurring after mastectomy and within 30 days after PMRT (P < 0.0001; HR 7.37, 2.78-19.55) were significantly associated with MRC. Dosimetric characteristics (excluding boost), including maximum chest wall hot spot ≥ 5464 cGy (P = 0.003; HR 4.08, 1.60-10.41), D 2cc ≥ 5410 cGy (P = 0.01; HR 3.51, 1.37-8.95), D 0.03cc ≥ 5420 cGy (P = 0.01; HR 4.73, 1.46-15.33), V100% ≥ 640 cc (P = 0.01; HR 2.72, 1.26-5.91), V105% ≥ 250 cc (P = 0.003; 2.58, 1.39-4.77), and V108% ≥ 3.5 cc (P = 0.01; HR 2.97, 1.25-7.07) were significantly associated with MRC. Patients undergoing PMRT and implant-based reconstruction are at significant risk of MRC. Obesity, infection within 30 days of PMRT, increased treatment volume, and plan heterogeneity further increase this risk. Additional studies are needed to validate these findings and determine dosimetric constraints or other prophylactic measures that can limit complication risk. [ABSTRACT FROM AUTHOR]