onc brain

About · curated by Nick Boehling, MD · @nb2276

    CNS

    6 studies across 5 dates

    2026-07-13

    EANO Consensus Statement on Radiation Necrosis

    TL;DRDelphi consensus (20 experts): 53/57 statements reached ≥80% agreement; perfusion MRI + amino-acid PET to distinguish RN from recurrence, bevacizumab for steroid-refractory RN.

    Why it mattersRadiation oncology

    The RT-actionable core is the recurrence-vs-necrosis call: perfusion MRI (DSC/DCE) plus amino-acid PET (FET/DOPA/MET) over standard MRI, with histopathology still gold standard. For symptomatic RN, bevacizumab (5-10 mg/kg q2-3wk) is recommended for steroid-refractory cases and noted effective even at low doses.

    8 details 5 trials watching
    Design

    Three-round Delphi among 20 EANO experts; consensus set at ≥80% agreement on a 5-point Likert scale. Reached consensus on 53 of 57 statements.

    Results

    RN occurs in 4-30% after focal RT, typically 6-24 mo post-treatment. Perfusion MRI (DSC/DCE) plus amino-acid PET (FET/DOPA/MET) preferred for the RN-vs-recurrence call; histopathology remains gold standard.

    Discussion

    Symptomatic RN: dexamethasone (e.g. 8mg, rapid taper), then bevacizumab (5-10 mg/kg q2-3wk) for steroid-refractory/dependent disease (>4wk); surgery preferred when feasible, LITT an option. Bevacizumab noted effective even at low doses.

    Limitations

    No Level 1 evidence; expert opinion only. Panel explicitly flags the need for prospective randomized trials in symptomatic RN.

    Monday clinic

    In a brain-tumor pt 6-24 mo post-RT with a new or enlarging enhancing lesion, this supports advanced imaging (perfusion MRI + amino-acid PET) before calling recurrence; it does not apply to asymptomatic necrosis beyond serial observation.

    Open questions
    📚 Sources · 📄 1 paper
    📄 PAPER Duerinck, Johnny; Van Den Bent, Martin; Brandal, Petter et al. · Neuro-Oncology (2026-07)
    The European Association for Neuro-oncology (EANO) Consensus Statement on Radiation Necrosis
    doi
    Abstract
    Abstract Introduction Radiation necrosis (RN) complicates neuro-oncological care, mimicking tumor recurrence and lacking high-level evidence for standardized management. Methods A European Association for Neuro-Oncology (EANO) expert panel utilized a three-round Delphi process to create a comprehensive expert opinion document based on the available current scientific evidence. A series of statements, derived from the published literature were created by the experts in each field. Consensus was defined as ≥ 80% agreement using a 5-point Likert scale. Results After three rounds among 20 experts that included adaptation of statements, the Delphi process reached a consensus (≥80% agreement) on 53 statements out of 57. RN occurs in 4% to 30% of patients, typically appearing 6 to 24 months after radiotherapy for primary (glial) or metastatic brain tumors. Experts identified perfusion MRI and amino acid PET as the most suitable imaging modalities for differentiation from tumor recurrence. While histopathology remains the gold standard, identifying viable tumor cells in irradiated gliomas is challenging due to overlapping cytological features with reactive glia. For symptomatic management, corticosteroids may be tried, and bevacizumab is recommended for corticosteroid-refractory cases, with evidence suggesting profound efficacy even at low doses. Surgery is considered effective for rapid symptom relief and definitive diagnosis in accessible lesions. Laser Interstitial Thermal Therapy (LITT) can be considered an additional treatment option for symptomatic RN. Conclusions Despite the absence of Level 1 evidence, these Delphi-survey-formulated recommendations provide actionable guidance for clinical practice. There is a need for prospective randomized trials focusing on symptomatic RN.

    Supportive Consensus / guideline

    2026-07-07

    Confirmatory

    EORTC 22033-26033

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

    Progression-free survival surrogate

    No PFS or OS difference between arms

    ns regardless of molecular subtype

    TL;DRNo PFS/OS difference between first-line RT and TMZ in high-risk WHO grade 2 LGG; only IDH-wildtype favored TMZ (HR 0.47).

    Why it mattersRadiation oncology

    Upfront RT (28 × 1.8 Gy) and TMZ were survival-equivalent in every IDH-mutant subtype, including radiosensitive codeleted oligodendroglioma (OS 12.9 vs 14.9 yr, HR 0.88). The lone modality signal favored TMZ in IDH-wildtype (OS 4.7 vs 2.5 yr, HR 0.47), so molecular status, not modality, gates the first-line choice; combined-modality is now standard for IDH-mutant astrocytoma.

    6 details 2 trials watching
    Design

    Phase 3 RCT (EORTC 22033-26033 with NCIC-CTG/TROG/MRC-CTU), N=478 clinical high-risk WHO grade 2 LGG, randomized to RT vs dose-dense TMZ. Mature results, with post-hoc 2021 WHO molecular reclassification in 73% (351/478).

    Radiotherapy

    RT 28 × 1.8 Gy, standard fractionation, as the single-modality comparator arm.

    Regimen

    Dose-dense TMZ 75 mg/m² once daily, 21 of 28 days, up to 12 cycles.

    Endpoints

    Primary: progression-free survival; overall survival co-reported. No significant difference in PFS or OS between arms.

    Results

    Neither PFS nor OS differed by arm overall; molecular-subgroup OS is in the detail table, with only IDH-wildtype favoring TMZ.

    Subgroup (2021 WHO), nRT OSTMZ OSHR (95% CI), p
    Astrocytoma IDHmt non-codel, n=1786.6-6.7 yr6.6-6.7 yrHR CI 0.67-1.44, P=.93
    Oligo IDHmt codel, n=10912.9 yr (9.4-NR)14.9 yr (10.1-NR)0.88 (0.52-1.49), P=.63
    IDH-wildtype, n=642.5 yr (1.8-3.3)4.7 yr (2.2-7.2)0.47 (0.27-0.82), P=.0068
    vs leading data

    Combined-modality (RT + chemo) was not tested here but has since become standard for IDH-mutant astrocytoma (e.g. RTOG 9802, RT+PCV).

    Applies to
    high-risk WHO grade 2 LGG facing a single-modality first-line choice
    Does not represent combined-modality candidates, now the standard for IDH-mutant astrocytoma.
    Limitations

    Molecular subtypes are post-hoc reclassification (tissue in 73%); the IDH-wildtype subgroup is small (n=64). Combined-modality untested.

    Rationale

    Mature phase 3; the null modality comparison confirms combined-modality's rise as SOC. Molecular subgroups reclassified post-hoc, so no single-modality practice change lands.

    Monday clinic

    In high-risk WHO grade 2 IDH-mutant glioma, this supports that first-line RT versus TMZ monotherapy does not change PFS or OS; it does not extend to IDH-wildtype tumors, where a small post-hoc subgroup favored TMZ.

    Open questions
    📚 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

    Radiation Curative Phase 3 RCT Confirmatory

    2026-06-09

    Caveats dominate

    FIRESTORM

    ForHigh-risk meningioma: WHO grade 2 STR or recurrent, postop RT

    TL;DR5-yr PFS 65.8% vs 38.8% favoring dose-escalated RT (BED ≥79.2 Gy), HR 0.40; OS not improved.

    Why it mattersRadiation oncology

    The trade-off is the actionable read: escalating to BED ≥79.2 Gy (≈66 Gy/33 fx) roughly doubled 5-yr PFS (65.8% vs 38.8%) but tripled any-grade radionecrosis (33.9% vs 13.2%), with severe RN unchanged (5.1% vs 3.2%) and no OS gain. Benefit was largest after subtotal resection.

    9 details 3 trials watching
    Design

    Individual patient-level meta-analysis pooling 7 institutions, N=248 (59 DE-RT, 189 SD-RT). Retrospective, non-randomized; compared by Kaplan-Meier, Cox multivariable, and IPTW propensity analysis.

    Population & inclusion

    High-risk meningioma: 75.8% WHO grade 2, 41.5% recurrent (grade 3 the remainder), 75.2% subtotal resection.

    Radiotherapy

    DE-RT defined as biologically effective dose ≥79.2 Gy (equivalent 66 Gy/33 fx); SD-RT comparator conventionally fractionated 59.4 Gy/33 fx or 60 Gy/30 fx. Mixed photon/carbon vs photon-alone DE-RT showed no PFS difference (81.3% vs 92.0% at 3y, P=.34).

    Endpoints

    Primary: progression-free survival, DE-RT vs SD-RT. Also overall survival and CNS radionecrosis.

    Results

    OS not improved despite the PFS gain: 5-yr OS 83.8% vs 68.4% (P=.056 UVA), non-significant on MVA (HR 0.66, P=.27) and IPTW (HR 0.77, P=.42).

    EndpointDE-RTSD-RT
    3-yr PFS86.4%55.6%
    5-yr PFS65.8%38.8%
    Adjusted HR (MVA)0.40 (0.24-0.69), P=.001ref
    IPTW HR0.45 (0.24-0.83), P=.01ref
    RadionecrosisDE-RTSD-RT
    Any grade33.9% (20/59)13.2% (25/189)
    Grade 3+5.1%3.2%
    Safety

    Any-grade radionecrosis higher with DE-RT (33.9% vs 13.2%, P=.001) but grade 3+ similar (5.1% vs 3.2%); most RN was low-grade.

    vs leading data

    Standard-dose postoperative meningioma RT (RTOG-0539 high-risk 60 Gy, EORTC-22042 60 Gy) sits at/below this cohort's SD-RT arm; the dose-response signal here motivates the ongoing randomized escalation question.

    Applies to
    high-risk meningioma (WHO grade 2 subtotally resected or recurrent, plus grade 3) receiving postoperative fractionated RT
    Does not represent gross-totally-resected grade 1 disease, upfront observation, or radiosurgery-only management.
    Limitations

    Retrospective non-randomized pooling: DE-RT allocation confounded, IPTW mitigates but cannot fully adjust. PFS gain without OS benefit; prior-RT and grade imbalance across arms.

    Rationale

    Retrospective non-randomized IPD pooling; DE-RT allocation confounded despite IPTW. PFS-only gain, no OS benefit. Signal supports escalation but needs randomized confirmation.

    Monday clinic

    In high-risk meningioma (WHO grade 2, subtotally resected or recurrent) receiving postoperative RT, this supports a higher dose (BED ≥79.2 Gy) for local control; it does not extend to gross-totally-resected grade 1 disease or establish an OS benefit.

    Open questions
    📚 Sources · 📄 1 paper
    📄 PAPER Singh, Raj; Koempel, Andrew; French, Beck et al. · International Journal of Radiation Oncology*Biology*Physics (2026-07)
    Improved Progression-Free Survival Following Dose-Escalated Versus Standard-Dose Postoperative Radiation Therapy for High-Risk Meningiomas: An International Multicenter Individual Patient–Level Meta-Analysis (FIRESTORM)
    PMID 41956162 → doi
    Abstract
    PURPOSE: We performed an individual patient-level meta-analysis of high-risk meningiomas to compare the outcomes of dose-escalated radiation therapy (DE-RT) versus standard-dose postoperative radiation therapy (SD-RT).<br/><br/>METHODS AND MATERIALS: A total of 7 institutions participated. DE-RT was defined as treatment with a biologically effective dose of &#x2265;79.2 Gy (equivalent of 66 Gy in 33 fractions). We compared progression-free survival (PFS) with DE-RT versus SD-RT via Kaplan-Meier analysis and log-rank t tests, a Cox proportional hazards multivariable model, and propensity score analyses with inverse probability of treatment weighting (IPTW). We also compared incidences of central nervous system radionecrosis (RN) with DE-RT versus SD-RT.<br/><br/>RESULTS: The analysis included 248 patients with high-risk meningioma (59 received DE-RT and 189 received SD-RT). One hundred and eighty-eight cases (75.8%) were World Health Organization grade 2, and 103 cases (41.5%) were recurrent meningiomas. Extent of resection was subtotal resection in 182 of 248 (75.2%). Three- and 5-year PFS rates were 62.8% (95% CI, 55.8%-69.0%) and 45.0% (95% CI, 37.3%-52.3%), respectively. DE-RT was associated with superior PFS rates (P = .0022), with 3-year (86.4% vs 55.6%) and 5-year (65.8% vs 38.8%) PFS rates favoring DE-RT. On multivariable analysis, DE-RT was associated with superior PFS (hazard ratio, 0.40; 95% CI, 0.24-0.69; P = .001). On IPTW, DE-RT continued to be associated with superior PFS (hazard ratio, 0.45; 95% CI, 0.24-0.83; P = .01). A greater incidence of any grade RN was observed following DE-RT (20 of 59; 33.9%) versus SD-RT (25 of 189; 13.2%) (P = .001) but with similar grade 3 or greater RN events (DE-RT 5.1% vs SD-RT 3.2%).<br/><br/>CONCLUSIONS: DE-RT resulted in superior PFS for patients with high-risk meningiomas over SD-RT without an increase in severe toxicities.

    Radiation Curative Meta-analysis Caveats dominate

    Confirmatory

    RTOG 0539 NCT00895622

    ForWHO grade 1-3 meningioma, post-resection, newly diagnosed or recurrent

    TL;DR10-yr PFS 72.2% intermediate-risk (54Gy) and 42.5% high-risk (60Gy) meningioma on adjuvant RT; low-risk observed 85.2%.

    Why it mattersRadiation oncology

    The RT read is patient selection: low-risk grade 1 (GTR/STR) observed carried only 8.9% 10-yr cumulative progression, backing omission, while intermediate-risk earns 54Gy/30fx adjuvant. High-risk 60Gy still leaves 39.3% 10-yr progression, marking the ceiling of adjuvant RT alone in grade 2/3 disease.

    7 details 5 trials watching
    Design

    Prospective phase 2, multi-institutional (NRG/RTOG), risk-adapted by WHO grade, extent of resection, and recurrence status. 244 consented, 165 protocol-treated. Central pathology review; data cutoff 8/15/2023.

    Population & inclusion

    Adults ≥18, Zubrod 0-1, histologically confirmed unifocal WHO grade 1-3 meningioma, any resection extent. Low-risk n=60, intermediate n=52, high-risk n=53.

    Radiotherapy

    Intermediate-risk 54 Gy and high-risk 60 Gy, both in 30 fractions, adjuvant. Low-risk received no RT (observation). No hypofractionation or SRS arm.

    Endpoints

    Primary (3-yr PFS) reported previously. This analysis reports long-term PFS, OS, and cumulative incidence of progression (competing-risk) at ~12-yr median follow-up.

    Results

    Per-cohort 10-yr PFS, OS, and cumulative-incidence values are in the table above. Median PFS not reached for low- and intermediate-risk.

    Cohort (management)10-yr PFS10-yr OS10-yr cum. incidence progression
    Low-risk, observed85.2%94.1%8.9% (3.2-18.2)
    Intermediate, 54Gy72.2%84.7%21.2% (10.8-33.9)
    High-risk, 60Gy42.5%51.1%39.3% (25.8-52.5)
    Safety

    RT-attributable grade 3+ toxicity 9.6% (intermediate, 5/52) and 15.1% (high-risk, 8/53). The observed low-risk cohort carried no RT toxicity.

    vs leading data

    No randomised RT-vs-observation trial in grade 2 meningioma has reported. ROAM/EORTC-1308 and NRG-BN003 (GTR grade 2) remain open; RTOG 0539 is the prospective benchmark.

    Applies to
    newly diagnosed or recurrent unifocal WHO grade 1-3 meningioma across resection extents, risk-stratified
    Does not represent multifocal meningioma or patients treated with SRS or hypofractionation.
    Limitations

    Each risk cohort is single-arm, no randomised RT-vs-observation comparison; modest per-cohort N (~50-60); grading predates molecular integration into WHO CNS grading.

    Rationale

    Prospective multi-institutional risk-adapted phase 2, 12-yr mature f/u, sets RT patient-selection benchmark. Each cohort single-arm; no randomised RT-vs-observation comparison.

    Monday clinic

    In newly diagnosed grade 1 meningioma after gross or subtotal resection, this supports observation over adjuvant RT; it does not soften the case for 54-60Gy in recurrent grade 1, grade 2, or grade 3 disease.

    Open questions
    📚 Sources · 📄 1 paper
    📄 PAPER Kotecha, Rupesh; Polley, Mei-Yin; Vogelbaum, Michael A. et al. · Journal of Clinical Oncology (2026-05)
    Long-Term Analysis of NRG Oncology RTOG 0539: A Phase II Trial of Observation for Low-Risk Meningioma and Radiotherapy for Intermediate- and High-Risk Meningioma
    doi
    Abstract
    NRG Oncology RTOG 0539 was a prospective phase II trial of risk-adapted radiotherapy for patients with WHO grade 1-3 meningioma. Low-risk (group 1, n = 60) was defined as a grade 1 tumor after gross total resection or subtotal resection (GTR/STR) and prospectively monitored. Intermediate-risk (group 2, n = 52) was defined as recurrent grade 1 or newly diagnosed grade 2 tumor after GTR and treated with radiotherapy (54 Gy). High-risk (group 3, n = 53) included a newly diagnosed grade 2 tumor after STR, newly diagnosed grade 3 tumor, or recurrent grade 2 or 3 tumor and treated with radiotherapy (60 Gy). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The median follow-up times for the low-, intermediate-, and high-risk cohorts were 12.1, 12.0, and 11.1 years, respectively. The 10-year PFS and OS rates for the low-, intermediate-, and high-risk cohorts were 85.2% and 94.1%, 72.2% and 84.7%, and 42.5% and 51.1%, respectively. Five patients (9.6%) and eight patients (15.1%) had a grade 3+ toxicity attributed to radiotherapy in the intermediate- and high-risk cohorts, respectively. The long-term outcomes using this risk-adapted approach support observation for low-risk patients, inform radiotherapy patient selection and practice standards for intermediate- and high-risk patients, and provide comparative benchmarks for future trials.

    Radiation Curative Phase 2 trial Confirmatory

    2026-05-30 ASCO Annual Meeting 2026

    Challenges SOC

    ROADS

    ForResected brain metastasis > 2 cm, post-op cavity RT candidates

    Time to surgical bed recurrence local control

    NR vs 17 mo

    Surg bed recurrence 1% GammaTile vs 12% SRS

    TL;DRSurgical bed recurrence 1% vs 12% and 2yr OS 62% vs 36% favoring intraoperative GammaTile brachytherapy over post-op SRS for resected brain mets >2cm.

    Why it mattersRadiation oncology

    The safety tradeoff the headline buries: leptomeningeal disease ran 10% with GammaTile vs 3% with SRS, even as surgical-bed recurrence fell to 1% vs 12%. Radiation necrosis was comparable (8% vs 7%). This moves the intraoperative-brachytherapy-vs-staged-cavity-SRS decision for resected mets >2 cm, where SRS local control is weakest.

    ROADS
    EndpointGammaTileSRS
    Time to surg bed recurrenceNR17 mo
    Surg bed recurrence-free survivalNR11 mo
    2-yr OS62%36%
    8 details 2 trials watching
    Design

    Randomized trial, N=230, resected brain metastasis > 2 cm. GammaTile (Cs-131 collagen-tile brachytherapy) placed in the cavity at resection vs post-op stereotactic radiosurgery. ASCO 2026 final results. Primary: time to surgical bed recurrence and surgical-bed recurrence-free survival.

    Population & inclusion

    Resected brain metastasis > 2 cm, the larger-cavity setting where single-fraction post-op SRS local control is weakest. Histology / primary tumor not specified in source.

    Radiotherapy

    Experimental: intraoperative permanent Cs-131 seed brachytherapy (GammaTile) at resection. Control: post-op cavity SRS. Dose, fractionation, and cavity margin not reported in source.

    Results

    Both primary endpoints and 2yr OS favored GammaTile. Safety: radiation necrosis comparable (8% vs 7%), leptomeningeal disease higher with brachytherapy (10% vs 3%).

    vs leading data

    Post-op cavity SRS is the current standard for resected brain mets (N107C, Mahajan). ROADS challenges it, favoring intraoperative brachytherapy on local control.

    Applies to
    pts with a resected brain metastasis > 2 cm who are candidates for post-op cavity radiotherapy
    Does not represent intact (unresected) brain mets or resection cavities ≤ 2 cm.
    Limitations

    Abstract-only, not yet peer-reviewed; open-label. The 2yr OS advantage is large for a local therapy and OS was not a stated primary endpoint, raising the question of baseline arm imbalance.

    Rationale

    Randomized, primary endpoint (surg bed control) hit favoring intraop brachy over the post-op SRS standard; but abstract-only, open-label, and the large OS gain warrants scrutiny.

    Monday clinic

    In pts with a resected brain metastasis >2 cm needing cavity radiotherapy, this supports intraoperative brachytherapy as an alternative to post-op SRS for local control; it does not extend to intact (unresected) mets or cavities ≤2 cm.

    Open questions
    📚 Sources · 🐦 1 tweet

    Radiation Palliative Phase 3 RCT Challenges SOC ASCO Annual Meeting 2026

    2026-05-29 ASCO Annual Meeting 2026

    Confirmatory

    Wait or Treat? NCT05236946

    ForAsymptomatic brain mets, EGFR/ALK-mutant metastatic NSCLC, on TKI + chemo

    Intracranial PFS local control

    Sub-HR 0.35

    95% CI 0.21-0.59, p<0.001; favors upfront RT

    TL;DRUpfront cranial RT cut 2y intracranial progression (21.7% vs 50%, sub-HR 0.35) but no OS gain; survival numerically favored delayed (HR 1.45).

    Why it mattersRadiation oncology

    The primary endpoint actually favored upfront RT (2y intracranial progression 21.7% vs 50%, sub-HR 0.35), yet OS trended toward delayed (2y 48% vs 60%) with 6% radiation necrosis vs none. Better CNS control bought no survival and added toxicity, so upfront cranial RT can be safely deferred to intracranial progression.

    Wait or Treat?
    EndpointUpfront RTDelayed RT
    Events2047
    1-yr intracranial PD8.7% (2.9-14.5)25.7% (16.8-34.7)
    2-yr intracranial PD21.7% (12.6-30.8)50% (39.2-60.9)
    Sub-HR (95% CI)0.35 (0.21-0.59), p<0.001ref
    8 details 4 trials watching
    Design

    Phase 3 open-label RCT, 1:1, N=208 (105 upfront cranial RT vs 103 delayed) at a single center (Tata Memorial). Median follow-up 30.6 mo; stratified by GPA and synchronous vs metachronous BM.

    Population & inclusion

    Metastatic EGFR- or ALK-mutant NSCLC with radiologically measurable, completely asymptomatic brain metastases, ECOG 0-2. Both arms received TKI + chemotherapy.

    Radiotherapy

    Delayed arm held cranial RT until intracranial progression or patient request, with MRI brain q3mo for year 1 then q6mo. RT dose, fractionation, and technique (SRS vs WBRT) not reported in source.

    Endpoints

    Primary: intracranial PFS. Secondary: OS, PFS, toxicity, ORR, neurocognition, PROM.

    Results

    Primary endpoint met for intracranial control but did not translate to survival; the OS trend and radiation-necrosis signal both favored deferral. See the intracranial-progression figure and survival table for effect sizes.

    vs leading data

    First randomized evidence on RT timing in this population. Consistent with the CNS-active TKI era (osimertinib, alectinib, lorlatinib), where strong systemic intracranial control supports deferring RT.

    Applies to
    asymptomatic brain metastases in EGFR/ALK-mutant metastatic NSCLC on TKI plus chemotherapy
    Does not represent symptomatic brain mets, oncogene-negative NSCLC, or pts needing immediate neurologic intervention.
    Limitations

    Open-label and single-institution. Powered for intracranial PFS, not OS, so the survival and necrosis signals favoring deferral are secondary. RT technique not reported.

    Rationale

    Randomized phase 3, primary intracranial-PFS endpoint met, but no OS benefit and less necrosis with deferral; backs the emerging TKI-first, defer-RT approach in oncogene-driven NSCLC.

    Monday clinic

    In asymptomatic brain metastases from EGFR/ALK-mutant metastatic NSCLC on TKI plus chemo, this supports deferring cranial RT until intracranial progression; it does not extend to symptomatic brain mets or oncogene-negative NSCLC.

    Open questions
    📚 Sources · 🐦 3 tweets

    Radiation Palliative Phase 3 RCT Confirmatory ASCO Annual Meeting 2026