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About · curated by Nick Boehling, MD · @nb2276

    2026-07-07

    digest generated 2026-08-11

    SUPREMO: 10yr OS 81.4% vs 81.9% (HR 1.04) with CWI omission, chest-wall recurrence 1.1% vs 2.5%, PMRT is optional in intermediate-risk pN0-pN1.
    TL;DR
    Two trials narrow RT's field and one widens it: SUPREMO says the chest wall can be left alone after mastectomy in intermediate-risk disease (recurrence halved, but under 2 points absolute), while ARTO says every met site should be treated in omCRPC (mOS NR vs 50 mo, HR 0.55). Breast and prostate carried the day; EORTC 22033 leaves grade 2 LGG with a negative trial and a post hoc IDHwt signal.

    Breast

    The de-escalation question the EBCTCG meta-analysis could not answer for 1-3 node-positive disease on modern systemic therapy.

    Practice-changing

    SUPREMO

    ForPost-mastectomy pT1-2N1, pT3N0, or pT2N0 grade 3/LVI+ breast cancer

    Overall survival

    81.4% vs 81.9%

    HR 1.04, 95% CI 0.82-1.30, P=0.80; primary endpoint not met

    TL;DR10yr OS 81.4% vs 81.9% (HR 1.04, 0.82-1.30, p=0.80): PMRT omission safe in intermediate-risk pN0-pN1 post-mastectomy.

    Why it mattersRadiation oncology

    The RT read is the local-control trade: 1.1% vs 2.5% chest-wall recurrence, 29 events total, bought with 40-50 Gy to the chest wall in a population where OS was flat at 10 years. Nodal volumes were not routinely treated (SCF 97/808), so this speaks to chest wall alone, not to regional nodal irradiation.

    Monday clinic

    In a pT2N1 or pT3N0 mastectomy patient who has completed modern adjuvant systemic therapy, this supports discussing PMRT omission with an absolute chest-wall recurrence trade under 2 points; it does not address regional nodal irradiation or pN2-N3 disease.

    The longer read

    Also covered Jul 9

    9 details
    Design

    International phase 3 randomized trial (BIG 2-04 MRC/EORTC SUPREMO), 125 UK sites plus 27 European and 21 international sites. N=1607 ITT (808 CWI, 799 no CWI), randomized August 2006 to April 2013, database lock June 2024. Median follow-up 9.6 years.

    Population & inclusion

    "Intermediate-risk" post-mastectomy disease: pT1N1, pT2N1, pT3N0, or pT2N0 with grade 3 and/or LVI. All had mastectomy, an axillary procedure, and systemic therapy. Baseline systemic exposure: 85% chemotherapy, 79% endocrine, 19% trastuzumab.

    Radiotherapy

    Chest wall 40 to 50 Gy in the irradiation arm. Nodal volumes were not part of the randomized question: supraclavicular fossa treated in only 97/808 irradiated patients, internal mammary chain in 12/808. Twelve patients in the no-irradiation arm received SCF treatment.

    Endpoints

    Primary: overall survival at 10 years. Secondary: chest-wall recurrence, regional recurrence, disease-free survival, distant metastasis-free survival, cause of death, radiation-related adverse events.

    vs leading data

    The historic case for postmastectomy RT in node-positive disease rests on the EBCTCG overview, where the locoregional-control gain translated into a mortality benefit. SUPREMO tests that inheritance in the 1-3 node and high-risk node-negative band under contemporary systemic therapy and finds the recurrence signal preserved (HR 0.45) but the survival signal absent (HR 1.04).

    Applies to
    post-mastectomy pT1-2N1, pT3N0, and pT2N0 grade 3 or LVI-positive disease treated with modern adjuvant systemic therapy and chest-wall-only irradiation
    Does not represent pN2-N3 disease, patients requiring regional nodal irradiation, or those who did not receive systemic therapy.
    Limitations

    The chest-wall recurrence benefit rests on 29 events total with a CI upper bound of 0.99, so the point estimate is unstable. Accrual ran 2006-2013, predating routine dual HER2 blockade, extended adjuvant CDK4/6 inhibition, and current genomic risk stratification, all of which lower the baseline recurrence rate this trial was powered against.

    Discussion

    A flat OS with a halved chest-wall recurrence is the signature of a locoregional intervention operating below the threshold where local control converts into survival. At 1.1% vs 2.5%, the absolute chest-wall event rate in both arms is low enough that no plausible salvage-to-mortality pathway could move a 10-year OS curve. The result reframes PMRT in this band as a local-control decision to be weighed against RT morbidity, not as a survival decision.

    Results
    EndpointCWINo CWIHR (95% CI)
    Overall survival (1°)81.4%81.9%1.04 (0.82-1.30), p=0.80
    Disease-free survival76.2%75.5%0.97 (0.79-1.18)
    Distant MFS78.2%79.2%1.06 (0.86-1.31)
    Chest-wall recurrence9 (1.1%)20 (2.5%)0.45 (0.20-0.99)
    Enrolment
    CONSORT flow
    Randomized 1607
    ↓
    Chest-wall irradiation
    allocated 808
    10yr OS 81.4%
    No chest-wall irradiation
    allocated 799
    10yr OS 81.9%
    Rationale

    Adequately powered phase 3, prespecified OS primary, 9.6yr median follow-up, modern systemic backbone. Supports omitting PMRT in a population where guidelines still often recommend it.

    Open questions
    • Does regional nodal irradiation carry the same null in pN1 disease
    • Which biomarker or genomic subgroup still benefits from chest-wall RT
    • Late cardiac and second-malignancy burden of the irradiated arm

    Sourced from Kunkler et al.

    📚 Sources · 📄 1 paper
    📄 PAPER Kunkler; Russell; Anderson et al. · The New England journal of medicine (2025-11)
    Ten-Year Survival after Postmastectomy Chest-Wall Irradiation in Breast Cancer.
    PMID 41191939 → doi full text (PMC) article →
    Abstract
    BACKGROUND: The role of postmastectomy chest-wall irradiation in patients with breast cancer classified as pN1 (with involvement of one to three axillary nodes) or pN0 (pathologically node negative) with additional risk factors is uncertain.<br/><br/>METHODS: In this international, phase 3, randomized trial, we evaluated the omission of chest-wall irradiation in women with "intermediate-risk" breast cancer - defined as cancer that was stage pT1N1, pT2N1, or pT3N0 or stage pT2N0 with a histologic grade of 3, lymphovascular invasion, or both (tumor size: T1, &#x2264;2 cm; T2, >2 cm to 5 cm; or T3, >5 cm) - that was treated with mastectomy, an axillary procedure, and systemic therapy. Patients were assigned to undergo chest-wall irradiation (40 to 50 Gy; the irradiation group) or not to undergo chest-wall irradiation (the no-irradiation group). The primary end point was overall survival, with 10 years of follow-up. Chest-wall recurrence, regional recurrence, disease-free survival, distant metastasis-free survival, causes of death, and radiation-related adverse events were also assessed.<br/><br/>RESULTS: The intention-to-treat population included 808 patients in the irradiation group and 799 in the no-irradiation group. The median follow up was 9.6 years. Overall survival was 81.4% with chest-wall irradiation and 81.9% with no chest-wall irradiation according to 10-year Kaplan-Meier estimates (hazard ratio for death, 1.04; 95% confidence interval [CI], 0.82 to 1.30; P&#x2009;=&#x2009;0.80). A total of 29 patients had a chest-wall recurrence - 9 (1.1%) in the irradiation group and 20 (2.5%) in the no-irradiation group (between-group difference, <2 percentage points; hazard ratio, 0.45; 95% CI, 0.20 to 0.99). Disease-free survival was 76.2% in the irradiation group and 75.5% in the no-irradiation group (hazard ratio for recurrence or death, 0.97; 95% CI, 0.79 to 1.18), and distant metastasis-free survival was 78.2% and 79.2%, respectively (hazard ratio for distant metastasis or death, 1.06; 95% CI, 0.86 to 1.31).<br/><br/>CONCLUSIONS: In this trial, chest-wall irradiation did not result in higher overall survival than no chest-wall irradiation among patients with intermediate-risk, early breast cancer treated with mastectomy and contemporary adjuvant systemic therapy. (Funded by the Medical Research Council and others; SUPREMO ISRCTN Clinical Study Registry number, 61145589.).
    📝 https://pmc.ncbi.nlm.nih.gov/articles/PMC7618363/

    Radiation Curative Phase 3 RCT Practice-changing

    Prostate

    Comprehensive MDT (BED ≥100 Gy, all sites) now has an OS signal in CRPC, not just the hormone-sensitive setting STOMP/ORIOLE tested.

    Early signal

    ARTO NCT03449719

    ForOligometastatic CRPC, ≤3 sites, no prior systemic therapy for CRPC

    TL;DRAdding SBRT to all met sites improved OS: median NR vs 50 mo, HR 0.55 (0.33-0.92), p=0.021 in omCRPC.

    Why it mattersRadiation oncology

    The prescription is the transferable part: 1-5 fractions at BED ≥100 Gy to ALL sites, not an index lesion, so this is ablative comprehensive MDT rather than debulking. That, plus a control arm on a modern ARSI backbone, is what separates ARTO from the hormone-sensitive MDT trials and moves the question from omission to comprehensive ablation in CRPC.

    Monday clinic

    In mCRPC with three or fewer sites and no prior CRPC-directed systemic therapy, this supports discussing comprehensive ablative SBRT alongside starting abiraterone; it does not extend to polymetastatic disease or to pts already progressing through an ARSI.

    The longer read

    Also covered Jun 12

    9 details 5 trials watching
    Design

    Multicentre phase 2 randomised open-label trial, 16 academic and community centres in Italy, 1:1 by random permuted blocks, stratified by centre, ECOG PS and number of metastases. Enrolment Jan 2, 2019 to Sept 7, 2022; median follow-up 53 months (IQR 43-60). ITT analysis.

    Population & inclusion

    Age ≥18 with prostate adenocarcinoma and metastatic castrate-resistant disease, no more than three metastatic sites, and no previous systemic therapy for the mCRPC state. N=157 (control 82, experimental 75). No race or ethnicity data collected.

    Regimen

    Both arms received ADT plus oral abiraterone acetate 1000 mg daily. The experimental arm added SBRT; the systemic backbone was identical, so the contrast isolates the radiotherapy.

    Radiotherapy

    SBRT delivered to all sites of metastatic disease in one to five fractions at a biologically effective dose ≥100 Gy. Comprehensive ablative intent, not treatment of an index lesion.

    Endpoints

    Primary: 6-month biochemical response (PSA decline ≥50% from baseline), reported previously. After the primary was met the power calculation was updated post-hoc for overall survival, finalised before unmasking; this report is an unplanned long-term OS analysis.

    Safety

    Most common grade 3-4 events were infectious complications (five control, zero experimental) and cardiovascular disorders (three each). One treatment-related death, in the control group, from myocardial failure. No excess grade 3-4 toxicity attributable to SBRT in the reported events.

    vs leading data

    STOMP and ORIOLE established MDT in hormone-sensitive oligometastatic disease without a systemic backbone, and SABR-COMET tested SABR across mixed histologies. ARTO is the randomised test in castrate-resistant disease with an ARSI given to both arms, which is the setting those trials leave open.

    Applies to
    oligometastatic CRPC with three or fewer sites, systemic-therapy-naive for the CRPC state, treated with abiraterone plus ADT and comprehensive ablative SBRT
    Does not represent polymetastatic CRPC, pts already progressing on an ARSI, or those in whom fewer than all lesions can be ablated to BED ≥100 Gy.
    Limitations

    Open-label with no sham, and the OS power calculation was revised after the primary read, so the alpha spent on this comparison is not the trial's original design. The experimental median is not reached, meaning the reported HR rests on a control-arm curve that is itself only partly mature at 53 months.

    Discussion

    A survival signal from comprehensive ablation on top of a modern ARSI backbone is the strongest randomised argument yet that MDT in CRPC is doing more than delaying PSA progression. What it does not settle is whether the benefit tracks the ablative dose, the completeness of coverage, or simply the favourable biology of pts whose disease stayed oligometastatic into castration resistance.

    Results

    See the OS figures above; per-arm event counts beyond the medians and HR are not reported in source.

    Enrolment
    CONSORT flow
    Randomized 157
    ↓
    AA/ADT alone (control)
    allocated 82
    mOS 50 mo
    SBRT + AA/ADT
    allocated 75
    mOS not reached
    Rationale

    Randomised phase 2, but the OS analysis is unplanned with post-hoc power revision and the primary endpoint was 6-month PSA response. N=157.

    Open questions

    Sourced from Francolini et al.

    📚 Sources · 📄 1 paper
    📄 PAPER Francolini; Di Cataldo; Caini et al. · The Lancet. Oncology (2026-07)
    SBRT plus abiraterone acetate and ADT versus abiraterone acetate and ADT in oligometastatic castrate-resistant prostate cancer (ARTO): long-term, unplanned overall survival analysis of an open-label, randomised, phase 2 trial.
    PMID 42372744 → doi
    Abstract
    BACKGROUND: The ARTO trial showed improved early clinical outcomes by adding metastasis-directed therapy (MDT), through stereotactic body radiotherapy (SBRT), to abiraterone acetate and ADT in oligometastatic castrate-resistant prostate cancer. The aim of this analysis is to explore the long-term impact of MDT on overall survival.<br/><br/>METHODS: ARTO was a multicentre, phase 2, randomised trial conducted in 16 academic and community centres across Italy. All patients included were aged 18 years or older and had a diagnosis of prostate adenocarcinoma with metastatic castrate-resistant prostate cancer, no more than three metastatic sites, and no previous systemic therapy for metastatic castrate-resistant prostate cancer status. Patients were randomly assigned (1:1, using random permuted blocks; stratified by treating centre, Eastern Cooperative Oncology Group performance status, and number of metastases) in an open-label design to androgen deprivation therapy plus oral abiraterone acetate 1000 mg daily with or without SBRT to all sites of metastatic disease (one to five fractions providing a biologically effective dose &#x2265;100 Gy). The primary endpoint was 6-month biochemical response (PSA decrease of &#x2265;50% compared with baseline) and has been reported previously. After meeting its primary endpoint, the power calculation was updated post-hoc to assess overall survival, finalised before data unmasking. We present an unplanned long-term follow-up focusing on overall survival. All analyses were performed on an intention-to-treat basis. The trial is registered on ClinicalTrials.gov (NCT03449719) and is now closed.<br/><br/>FINDINGS: Between Jan 2, 2019, and Sept 7, 2022, 157 patients were randomly assigned to the control (n=82) and experimental (n=75) groups. No data about race or ethnicity were collected. After a median follow up of 53 months (IQR 43-60), median overall survival was 50 months (95% CI 36-not reached [NR]) in the control group versus NR (55-NR) in the experimental group (HR 0&#xb7;55, 95% CI 0&#xb7;33-0&#xb7;92, p=0&#xb7;021). Most common grade 3-4 adverse events recorded were infectious complications (five in the control group vs zero in the experimental group) and cardiovascular disorders (three in the control group vs three in the experimental group). One treatment-related death occurred in the control group due to myocardial failure.<br/><br/>INTERPRETATION: The ARTO trial showed significant benefit in overall survival with the addition of MDT to systemic therapy versus systemic therapy alone.<br/><br/>FUNDING: Fondazione Radioterapia Oncologica.

    Combined Palliative Phase 2 trial Early signal

    CNS

    Mature EORTC 22033 data land in a molecular era that has already moved past the RT-vs-TMZ monotherapy question it asked.

    Confirmatory

    EORTC 22033-26033/NCIC-CTG/TROG/MRC-CTU

    ForClinical high-risk WHO grade 2 glioma, first-line, molecularly classified

    Progression-free survival surrogate

    No significant difference

    PFS and OS both ns between RT and TMZ arms; effect size not reported in source

    TL;DRMature phase III: RT (50.4Gy/28fx) vs dose-dense TMZ in high-risk WHO grade 2 LGG, no PFS or OS difference in any molecular subtype.

    Why it mattersRadiation oncology

    The RT-relevant read is what this does NOT license: single-modality TMZ never beat RT, so deferring 50.4Gy/28fx to spare late toxicity buys nothing on PFS or OS. IDH wild-type was the one split (OS 2.5 vs 4.7 yrs, HR 0.47 [0.27-0.82], P=.0068), post hoc and n=64, and those tumors now grade as GBM.

    Monday clinic

    In molecularly classified high-risk WHO grade 2 glioma being planned for first-line therapy, this supports neither leading modality over the other and does not address the combined-modality RT plus alkylator approach that is standard for IDH-mutant astrocytoma.

    The longer read
    8 details 2 trials watching
    Design

    Randomised phase III, four-group intergroup trial (EORTC/NCIC-CTG/TROG/MRC-CTU), N=478, comparing two single-modality first-line strategies. This is the mature analysis; a post hoc reclassification to 2021 WHO criteria was possible in 73% (351/478) with analyzable tissue.

    Population & inclusion

    Clinical high-risk WHO grade 2 low-grade glioma, treatment-naive. Post hoc molecular strata: IDHmt/1p19q non-codeleted astrocytoma n=178, IDHmt/1p19q codeleted oligodendroglioma n=109, IDH wild-type n=64.

    Radiotherapy

    Standard fractionation, 28 × 1.8 Gy (50.4 Gy), delivered as the entire assigned treatment. No concurrent or adjuvant systemic therapy in the RT arm, which is the gap between this trial and how grade 2 glioma is treated now.

    Regimen

    Dose-dense temozolomide 75 mg/m² once daily, 21 of 28 days, up to 12 cycles, given as sole first-line therapy with RT withheld.

    Endpoints

    Primary: progression-free survival. Overall survival and differential response by molecular marker were the mature-analysis questions.

    Results

    No significant difference in PFS or OS between arms, and the null held across every molecular subtype except IDH wild-type, where OS favored TMZ.

    Subtype (n)RTTMZHR
    IDHmt astrocytoma, non-codel (n=178)6.6-6.7 yrs (either arm)6.6-6.7 yrs (either arm)0.67-1.44, P=.93
    IDHmt oligodendroglioma, 1p/19q codel (n=109)12.9 yrs (9.4-NR)14.9 yrs (10.1-NR)0.88 (0.52-1.49), P=.63
    IDH wild-type (n=64)2.5 yrs (1.8-3.3)4.7 yrs (2.2-7.2)0.47 (0.27-0.82), P=.0068
    vs leading data

    RTOG 9802 established RT followed by PCV as the high-risk grade 2 benchmark, and combined-modality therapy is now standard for IDH-mutant astrocytoma. EORTC 22033 tested neither arm of that question: it asked which single modality to lead with, and answered that it does not matter.

    Applies to
    clinical high-risk WHO grade 2 glioma being assigned first-line single-modality therapy
    Does not represent pts receiving combined-modality RT plus alkylator, which is current standard of care for IDH-mutant astrocytoma and was not tested here.
    Limitations

    Molecular strata are post hoc in 73% of the enrolled population, so subtype comparisons carry both selection and multiplicity risk. The IDH wild-type finding rests on n=64, and under 2021 criteria those tumors would not be enrolled as grade 2 at all.

    Discussion

    The durable contribution is prognostic rather than therapeutic: median OS of 12.9-14.9 years in codeleted oligodendroglioma against 6.6-6.7 years in IDH-mutant astrocytoma quantifies how far molecular class outweighs modality choice. The finding that pts ≥40 fared better than <40 undercuts the age-40 cutoff that still gates high-risk definitions.

    Rationale

    Mature randomised phase III, primary endpoint negative in both arms and across molecular subtypes; the IDHwt survival difference is post hoc, n=64.

    Open questions

    Sourced from Baumert, Brigitta G. et al.

    📚 Sources · 📄 1 paper
    📄 PAPER Baumert, Brigitta G.; Hegi, Monika E.; van den Bent, Martin J. et al. · Journal of Clinical Oncology (2026-07)
    Temozolomide Versus Radiotherapy as First-Line Therapy for Low-Grade Glioma: Mature Results of a Randomized Phase III Trial (EORTC 22033-26033/NCIC-CTG/TROG/MRC-CTU)
    doi article →
    Abstract
    PURPOSE Prognosis in low-grade gliomas (LGGs) remains highly variable, and treatment-related late toxicity is a concern. This trial was comparing single-modality therapies in patients who often survive for years or decades and investigating differential responses according to molecular markers. METHODS Four hundred seventy-eight patients with clinical high-risk LGG (WHO grade 2) were randomly assigned to standard radiotherapy (RT; 28 × 1.8 Gy) or dose-dense temozolomide (TMZ; 75 mg/m 2 once daily × 21/28 days, up to 12 cycles). RESULTS There was no significant difference in progression-free survival or overall survival (OS) between study arms. Analyzable tumor tissue in 73% (351/478) of patients allowed for post hoc reclassification according to the 2021 WHO pathologic criteria. In astrocytoma, IDHmt/1p/19q noncodeleted (n = 178), median OS was similar, 6.6-6.7 years irrespective of arm (0.67-1.44, P = .93). In oligodendroglioma, IDHmt/1p/19q codeleted (n = 109), median OS was 12.9 years (9.4-not reached) with RT and 14.9 years (10.1-number of events not reached) with TMZ (hazard ratio [HR], 0.88 [0.52-1.49], P = .63). In 64 tumors without isocitrate dehydrogenase (IDH) mutations, survival favored the TMZ arm: OS 2.5 (1.8-3.3) versus 4.7 (2.2-7.2) years (HR, 0.47 [0.27-0.82], P = .0068). Patients age 40 years and older fared better than patients younger than 40 years, challenging the current notion of age alone as a negative prognostic factor. CONCLUSION The assigned initial treatment modality did not affect progression-free survival or OS, regardless of the molecular subtype. Combined-modality therapy was not tested in this trial but has since become a standard of care for IDH-mutant astrocytoma. With emerging novel therapeutic options, rational treatment strategies tailored at the individual clinical and pathologic recurrence risk profiles will be needed. The validity of an age cutoff as prognostic factor is challenged when tumors are molecularly classified.
    📝 https://ascopubs.org/doi/10.1200/JCO-25-02735

    Curative Phase 3 RCT Confirmatory