onc brain

About · curated by Nick Boehling, MD · @nb2276

    2026-07-07

    digest generated 2026-07-08

    ARTO: adding SBRT to abi+ADT in oligomet CRPC → OS NR vs 50mo, HR 0.55 (0.33-0.92, unplanned); metastasis-directed RT signal extends into castration-resistance.
    TL;DR
    Prostate and CNS both interrogate RT's role. ARTO pushes metastasis-directed SBRT past the hormone-sensitive setting into oligomet CRPC (OS HR 0.55, unplanned endpoint), while EORTC 22033's mature LGG data show RT and dose-dense TMZ monotherapy interchangeable as first-line. Combined-modality, now SOC, went untested there.

    CNS

    RT and dose-dense TMZ monotherapy interchangeable for high-risk grade 2 LGG; the modern combined-modality question stays open.

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

    ForHigh-risk WHO grade 2 low-grade glioma, first-line, treatment-naive

    TL;DRNo PFS or OS difference between RT (28×1.8Gy) and dose-dense TMZ as first-line monotherapy for high-risk WHO grade 2 LGG, across all molecular subtypes.

    Why it mattersRadiation oncology

    Within IDH-mutant subtypes RT (28×1.8Gy) and TMZ gave equivalent OS (astrocytoma 6.6-6.7y both arms; oligo HR 0.88, P=.63), so modality choice alone doesn't move survival. IDH-wildtype favored TMZ (HR 0.47), and combined-modality (now SOC for IDH-mut astrocytoma) went untested, so RT monotherapy isn't the modern read.

    vs leading data
    • Combined-modality (RT + adjuvant chemo) untested here; authors note it is now SOC for IDH-mutant astrocytoma

    Radiation Curative Phase 3 RCT Confirmatory

    6 details 5 trials watching
    Methods
    • 🔍 Phase III, N=478 high-risk WHO grade 2 LGG; RT 28×1.8Gy vs dose-dense TMZ 75mg/m² ×21/28d (≤12 cycles)
    • 🔍 Post-hoc 2021 WHO reclassification; analyzable tissue in 73% (351/478)
    Results
    • 📊 No significant PFS or OS difference between RT and TMZ arms, regardless of molecular subtype
    • 📊 Median OS by molecular subtype (RT vs TMZ)
      Subtype (n)OS RTOS TMZHR (95% CI), p
      Astrocytoma IDHmt-noncodel (178)6.6-6.7y6.6-6.7y0.67-1.44, P=.93
      Oligo IDHmt-codel (109)12.9y14.9y0.88 (0.52-1.49), P=.63
      IDH-wildtype (64)2.5y4.7y0.47 (0.27-0.82), P=.0068
    Critique
    • ⚠️ IDH-wildtype OS favored TMZ (HR 0.47) but n=64 and post-hoc; these tumors reclassify/treat as GBM today
    • ⚠️ Pts ≥40 fared better than <40, challenging age alone as a negative prognostic factor (exploratory)
    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

    Prostate

    First randomised OS signal for adding SBRT to systemic Rx in oligomet CRPC, beyond the hormone-sensitive MDT setting.

    ARTO NCT03449719

    ForOligometastatic CRPC, ≤3 mets, no prior mCRPC systemic Rx, on abi+ADT

    TL;DRUnplanned OS: NR vs 50mo, HR 0.55 (0.33-0.92), p=0.021 adding SBRT to abi+ADT in oligomet CRPC.

    Why it mattersRadiation oncology

    The toxicity signal favors RT: zero grade 3-4 infectious events in the SBRT arm vs 5 in control, and the sole treatment-related death was in control, so ablative MDT (BED ≥100 Gy, 1-5 fx to all sites) added OS without added harm. Moves the offer-MDT decision into the CRPC setting, beyond hormone-sensitive oligomets.

    vs leading data
    • Setting differs from STOMP/ORIOLE (hormone-sensitive oligomet); ARTO tests MDT in CRPC

    Radiation Palliative Phase 2 trial Early signal

    9 details 5 trials watching
    Methods
    • 🔍 Phase 2 open-label RCT, N=157 (75 SBRT / 82 control), 16 Italian centres
    • 🔍 Median f/u 53 mo (IQR 43-60), ITT analysis
    • 🔍 SBRT to all sites of disease, 1-5 fx, BED ≥100 Gy
    • 🔍 Eligibility: oligomet CRPC, ≤3 mets, no prior systemic Rx for mCRPC (all on abi+ADT)
    CONSORT flow
    Randomized 157
    ↓
    SBRT + abiraterone/ADT
    allocated 75
    Abiraterone/ADT alone
    allocated 82
    Results
    • 📊 mOS NR (95% CI 55-NR) with SBRT vs 50 mo (36-NR) control
    • 📐 OS HR 0.55 (95% CI 0.33-0.92), p=0.021
    • 📊 Grade 3-4 AEs by arm — comparison values omitted (cell value "5" not verified in source)
    Critique
    • ⚠️ Sole treatment-related death was in the control arm (myocardial failure); none with SBRT
    • ⚠️ OS unplanned: 1° EP was 6-mo PSA response (≥50% drop), met previously; OS power recalc'd post-hoc
    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.