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About · curated by Nick Boehling, MD · @nb2276

    2026-10-17

    digest generated 2026-10-18

    RT CHARM: PMRT at 42.56 Gy/16 fx noninferior to 50 Gy/25 fx for 24-mo reconstruction complications, 12.3% vs 10.2%, difference -2.1% (95% CI -6.5 to 2.2).
    TL;DR
    Single-site day carried by breast: RT CHARM supports moderate hypofractionation for PMRT with reconstruction, with 3-yr local/LR RFS 97.0% vs 96.2% (HR 1.01) and less G2 dermatitis (20% vs 42%). Caveats: wide 10% NI margin, median f/u 3.9 yr, underpowered reconstruction subgroups. Delayed reconstruction predicted complications (OR 2.96).

    Breast

    PMRT fractionation after mastectomy with reconstruction, where reconstruction-complication concern has kept many on 50 Gy/25 fx.

    Confirmatory

    RT CHARM (Alliance A221505) NCT03414970

    ForPost-mastectomy, T0-3 N0-2a M0, immediate or delayed reconstruction

    24-month reconstruction complication rate (composite) safety

    12.3% vs 10.2%

    difference -2.1% (95% CI -6.5 to 2.2), noninferiority p=0.0001

    TL;DR24-mo reconstruction complications 12.3% (42.56 Gy/16 fx) vs 10.2% (50 Gy/25 fx), difference -2.1% (95% CI -6.5 to 2.2); noninferior.

    Why it mattersRadiation oncology

    Reconstruction timing mattered more than fractionation: delayed reconstruction carried OR 2.96 for complications in either arm, while arm was not a predictor. LRR at 3 yr was 1.5% vs 2.2% and G2 dermatitis halved (20% vs 42%), so this supports 16 fx PMRT for reconstructed pts, including implant-only.

    Monday clinic

    In a woman needing PMRT for T0-3 N0-2a disease with immediate or planned delayed reconstruction, implant or autologous, this supports 16-fraction PMRT over 25 fractions; it does not extend to T4, N3, positive margins or prior thoracic RT. The longer read

    13 details 2 trials watching
    Design

    Unblinded 2-arm randomized noninferiority trial, 1:1, 209 US and Canadian sites, enrolled 2018-2021. N=898 enrolled, 825 evaluable (38 withdrew before RT, 35 ineligible). Median f/u 3.9 yr.

    Population & inclusion

    T0N1-2a, T1N1-2a, T2N1-2a or T3N0-2a, M0 after mastectomy, ECOG 0-1, with completed, ongoing or intended reconstruction. Excluded T4, N3, positive margins, collagen vascular disease, bilateral or prior ipsilateral cancer, prior thoracic RT. Median age 49, N1 76%, 51% neoadjuvant chemo.

    Radiotherapy

    50 Gy/25 fx over 5 wk vs 42.56 Gy/16 fx over 3 wk. IROC plan QA: 90% per-protocol or acceptable, 4% unacceptable. Target volumes and boost not stated in source excerpt.

    Endpoints

    Primary: composite reconstruction complications at 24 mo (wound healing, readmission, capsular contracture, unplanned reoperation, failure). NI margin 10%. Secondary: local/locoregional recurrence, acute and late toxicity.

    Results

    NI met in ITT and in the 631 pts who completed reconstruction within 18 mo. Fractionation effect did not appear to differ by reconstruction type or timing.

    Endpoint42.56 Gy/16 fx50 Gy/25 fxEffect
    24-mo reconstruction complications (ITT)12.3% (52/422)10.2% (41/403)-2.1% (95% CI -6.5 to 2.2), NI p=0.0001
    Completed reconstruction within 18 mo (n=631)12.6%10.4%-2.2% (95% CI -7.2 to 2.8), p=0.001
    3-yr local/LR recurrence, cumulative incidence1.5% (0.7-3.2)2.2% (1.1-4.3)Gray's test ns
    3-yr local/LR RFS97.0% (95.4-98.7)96.2% (94.3-98.2)HR 1.01 (0.53-1.96), p=0.97
    Acute G3+ non-reconstruction toxicity5.0%7.7%p=0.11
    Acute G2 dermatitis84 (20%)171 (42%)p<.0001
    Acute G3 dermatitis3 (1%)11 (3%)p=0.048
    Safety

    Acute G3+ non-reconstruction toxicity 5.0% vs 7.7% (p=0.11). RT-attributed toxicity similar except dermatitis, less frequent with hypofractionation. Late toxicity not statistically different.

    vs leading data

    Extends the hypofractionation evidence from post-lumpectomy trials (START, FAST-Forward) and post-mastectomy without reconstruction to the reconstructed chest wall, the setting where adoption lagged. Sits alongside FABREC, which tested the same 16-fraction schedule in implant reconstruction; RT CHARM adds autologous and delayed reconstructions.

    Applies to
    women needing PMRT for T0-3 N0-2a M0 disease with immediate or delayed, implant or autologous reconstruction
    Does not represent T4, N3, positive-margin or previously irradiated chest walls.
    Limitations

    Margin of 10% was powered on an assumed 25% control rate, but control ran 10.2%, so the margin is relatively generous. Unblinded assessment of complications; 35 pts lacked reconstruction forms at freeze. Late contracture and failure need longer f/u.

    Discussion

    Reconstruction timing (delayed OR 2.96) moved complication risk far more than fractionation. The remaining questions are long-term reconstruction durability and whether shorter schedules (5 fx) hold up in this setting.

    Rationale

    Randomized NI met across 209 sites with low LRR; wide 10% absolute margin against a 10.2% control rate and 3.9-yr f/u keep it short of practice-changing.

    Open questions

    Sourced from Poppe et al.

    📚 Sources · 📄 1 paper
    📄 PAPER Poppe; Le-Rademacher; Haffty et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2026-10)
    Randomized Trial of Hypofractionated Postmastectomy Radiation Therapy in Women With Breast Reconstruction (RT CHARM, Alliance A221505).
    PMID 42863096 → doi full text (PMC) article →
    Abstract
    PURPOSE: Patients with breast cancer requiring postmastectomy radiation therapy (PMRT) often desire breast reconstruction. Reconstructions can be adversely affected by PMRT, and fear of reconstruction complications has discouraged adoption of short-course radiation therapy used after lumpectomy. To fill the evidence gap, we conducted a noninferiority trial of hypofractionated versus conventional PMRT in patients undergoing breast reconstruction. The primary outcome was reconstruction complication rate, a composite of wound healing, readmission, capsular contracture, unplanned reoperation, and reconstruction failure.<br/><br/>METHODS: Women with unilateral invasive breast cancer with planned immediate or delayed reconstruction and PMRT were randomly assigned (1:1) to 50 Gy (25 fractions/5 weeks) or 42.56 Gy (16 fractions/3 weeks). This study was designed with a noninferiority margin of 10%, assuming a 2-year reconstruction complication rate of 25% with conventional PMRT. Randomization was stratified by immediate versus delayed and autologous versus implant-only reconstruction.<br/><br/>RESULTS: Between 2018 and 2021, 898 patients enrolled with a median follow-up of 3.9 years; 825 patients were evaluable for the primary end point. The 24-month reconstruction complication rates were 12.3% (52/422) with hypofractionated PMRT and 10.2% (41/403) with conventional PMRT, corresponding to an estimated difference of -2.1% (95% CI, -6.5 to 2.2). The complication rate was higher (regardless of arm) with implant-only versus autologous reconstruction (odds ratio = 1.65). There was no statistically significant difference in 36-month locoregional recurrence rates: 1.5% (95% CI, 0.7 to 3.2) with hypofractionated and 2.2% (95% CI, 1.1 to 4.3) with conventional PMRT. Acute and late toxicity rates were not statistically different.<br/><br/>CONCLUSION: A 16-fraction course of hypofractionated PMRT is safe and noninferior to conventional PMRT in women undergoing breast reconstruction after mastectomy.
    📝 https://pmc.ncbi.nlm.nih.gov/articles/PMC13660432/

    Radiation Curative Confirmatory