onc brain

About · curated by Nick Boehling, MD · @nb2276

    2026-07-29

    digest generated 2026-07-30

    DBCG Skagen 1: 40Gy/15fx noninferior to 50Gy/25fx for 3y arm lymphedema (8.0% vs 9.4%, OR 0.84) with regional nodal RT; LRR, distant recurrence, mortality equivalent.
    TL;DR
    Breast carried the day. DBCG Skagen 1 extends moderate hypofractionation to regional nodal irradiation, the last holdout where late-morbidity fear kept 50Gy/25fx alive: 15-fraction RNI held noninferior arm lymphedema (OR 0.84) with equivalent LRR, distant recurrence, and mortality. Watch BC mortality numerically favoring 50Gy (HR 1.25) on still-short 5.25y cancer f/u.

    Breast

    Hypofractionation moves into the regional nodal setting, where late-morbidity concern had kept 50Gy/25fx the default.

    Confirmatory

    DBCG Skagen Trial 1

    ForHigh-risk node-positive breast cancer with an indication for locoregional…

    Arm lymphedema at 3 years safety

    8.0% vs 9.4% (40 vs 50Gy)

    OR 0.84 (95% CI 0.62-1.14), P=.27; within +5pp NI margin

    TL;DR3y arm lymphedema 8.0% (40Gy/15fx) vs 9.4% (50Gy/25fx), OR 0.84, noninferior; LRR, distant recurrence, and mortality all equivalent.

    Why it mattersRadiation oncology

    Lymphedema, the specific barrier to hypofractionating regional nodal RT, was noninferior (8.0% vs 9.4% at 3y, OR 0.84), and locoregional recurrence was equivalent (HR 0.96), so 40Gy/15fx carries no local-control cost. Moves nodal-RT fractionation from 25 to 15 fx; watch the numerically higher BC-mortality HR 1.25 (CI crosses 1).

    6 details 2 trials watching
    Design

    Phase 3 noninferiority RCT, 1:1, N=2,908 ITT, 17 DBCG centers, accrued 2015-2021. Median follow-up 4.1y for lymphedema, 5.25y for cancer outcomes.

    Population & inclusion

    High-risk breast cancer with an indication for locoregional (regional nodal) radiotherapy. Median age 57 (range 23-86); arms balanced 1,464 (40Gy) vs 1,444 (50Gy).

    Radiotherapy

    Experimental 40Gy/15fx vs standard 50Gy/25fx to locoregional volumes including the regional nodes. The nodal coverage is what put lymphedema on the primary endpoint.

    Endpoints

    Primary: 3-year arm lymphedema, noninferiority margin max +5pp on an assumed 10% baseline. Secondary: locoregional recurrence, distant recurrence, breast-cancer and all-cause mortality within 8 years.

    Results

    Primary met: 3y lymphedema 8.0% vs 9.4%, OR 0.84 (0.62-1.14), P=.27. Oncologic HRs are in the detail table, all with CIs crossing 1.

    EndpointHR95% CI
    Locoregional recurrence0.960.62-1.51
    Distant recurrence1.100.89-1.37
    Breast cancer mortality1.250.93-1.66
    All-cause mortality1.080.85-1.36
    Applies to
    high-risk node-positive breast cancer receiving locoregional RT including the regional nodes
    Does not represent low-risk breast-only RT, already routinely hypofractionated.
    Limitations

    NI margin permitted up to a 50% relative lymphedema rise. BC-mortality point estimate favored 50Gy (HR 1.25, 0.93-1.66); 5.25y follow-up is still short for late fibrosis, cardiac, and mortality signals.

    Rationale

    Phase 3 NI RCT (N=2,908); primary lymphedema endpoint met within margin, oncologic outcomes equivalent. Supports increasingly-adopted hypofractionated locoregional/nodal RT.

    Monday clinic

    In high-risk node-positive breast cancer with a regional nodal RT indication, this supports 40Gy/15fx in place of 50Gy/25fx without excess lymphedema or locoregional recurrence; it does not address low-risk breast-only RT, already hypofractionated.

    Open questions

    Sourced from Offersen, Birgitte V. et al.

    📚 Sources · 📄 1 paper
    📄 PAPER Offersen, Birgitte V.; Alsner, Jan; Høgsbjerg, Kristine et al. · Journal of Clinical Oncology (2026-07)
    Hypo- Versus Standard Fractionated Locoregional Radiotherapy of Patients With High-Risk Breast Cancer in the Randomized Phase III Trial: The Danish Breast Cancer Group Skagen Trial 1
    doi article →
    Abstract
    PURPOSE Adjuvant radiotherapy for node-positive breast cancer (BC) using 50Gy/25fx has been Danish Breast Cancer Group (DBCG) standard. Hypofractionated radiotherapy based on 40Gy/15fx has been increasingly used; however, it is less frequently for locoregional therapy because of concern over more morbidity. DBCG Skagen trial 1 hypothesized that 40Gy/15fx did not cause more lymphedema than 50Gy/25fx 3 years after radiotherapy without compromising the pattern of failure. METHODS Skagen trial 1 is a phase III, noninferiority trial randomly assigning high-risk BC patients with an indication for locoregional radiotherapy to standard 50Gy/25fx versus experimental 40Gy/15fx. The primary end point was arm lymphedema; assuming a 3-year incidence with 50Gy/25fx of 10%, noninferiority was predefined to maximum 5% excess incidence with 40Gy/15fx. Accrual continued until 3-year estimates were reported in 1,012 patients. RESULTS Between 2015 and 2021, 2,963 patients consented from 17 centers; the intention-to-treat cohort comprised 2,908 patients: 1,444 had 50Gy (50%), and 1,464 had 40Gy (50%). The median age was 57 years (range, 23-86). At a median follow-up of 4.1 years (IQR, 3.0-5.0), the 3-year rates of lymphedema were 9.4% (50Gy) versus 8.0% (40Gy), odds ratio 0.84 (95% CI, 0.62 to 1.14), and P = .27, thus within the +5-percentage-point noninferiority margin. The median follow-up for cancer outcomes was 5.25 years (IQR, 4.26 to 6.96). Within 8 years, the hazard ratio for locoregional recurrence was 0.96 (95% CI, 0.62 to 1.51), that for distant recurrence was 1.10 (95% CI, 0.89 to 1.37), that for BC mortality was 1.25 (95% CI, 0.93 to 1.66), and that for all-cause mortality was 1.08 (95% CI, 0.85 to 1.36), thus all with no differences by random assignment. CONCLUSION 40Gy/15fx for locoregional radiotherapy of BC did not result in more lymphedema compared with 50Gy/25fx. There were no differences in locoregional or distant recurrences, breast cancer mortality, nor all-cause mortality between the random assignment arms.
    📝 https://ascopubs.org/doi/10.1200/JCO-25-02705

    Radiation Curative Phase 3 RCT Confirmatory