onc brain

About · curated by Nick Boehling, MD · @nb2276

    2026-10-24 ESMO Congress 2026

    digest generated 2026-10-25

    DeLLphi-305: mOS 21.1 vs 12.7 mo (HR 0.42) adding tarlatamab to durvalumab 1L maintenance in ES-SCLC, at interim OS analysis.
    TL;DR
    Prostate carried the day: DASL-HiCaP adds darolutamide to pelvic RT + ADT in very high-risk disease (4-yr MFS-CI 95% vs 88%, HR 0.42; interim, OS immature), and PEACE-1 at 8y holds OS HR 0.68 for abiraterone over ADT+docetaxel. Single-fraction SBRT edged 30 Gy/10 on 3-mo ITT pain response (38% vs 21%) for nonspine bone mets.

    Thoracic / Lung

    Tarlatamab moves into 1L ES-SCLC maintenance; ultra-central SBRT pooled G5 toxicity sits at 4%, mostly hemoptysis.

    Practice-changing

    DeLLphi-305 NCT06211036

    ForES-SCLC, no progression after 1L platinum-etoposide + durvalumab, ECOG 0-1

    Overall survival

    HR 0.42

    95% CI 0.32-0.54, P<0.001; mOS 21.1 vs 12.7 mo

    TL;DRmOS 21.1 vs 12.7 mo, HR 0.42 (0.32-0.54), adding tarlatamab to durvalumab 1L maintenance in ES-SCLC after chemo-IO induction.

    Why it mattersRadiation oncology

    Asymptomatic untreated brain mets were eligible and brain/liver mets were a stratification factor, so a cranial-disease subgroup read should exist; it is not in the source. The source also does not state whether consolidative thoracic RT or PCI was permitted, which gates how this maintenance backbone integrates with RT consolidation in ES-SCLC.

    Monday clinic

    In ES-SCLC with no progression after 4 cycles of platinum-etoposide + durvalumab and ECOG 0-1, including asymptomatic brain mets, this supports adding tarlatamab to durvalumab maintenance; it does not inform pts who progressed on induction or ECOG ≥2. The longer read

    DeLLphi-305
    MetricTarlatamab + Durvalumab (n = 282)Durvalumab (n = 281)
    Median OS, mo (95% CI)21.1 (20.8-NE)12.7 (11.2-14.8)
    Median FU, mo15.916.1
    HR (95% CI); P0.42 (0.32-0.54); P < 0.001ref
    +2 more figures
    PFS: HR 0.34 (0.28-0.42), P<0.001. Median FU 13.9 mo.
    PFS: HR 0.34 (0.28-0.42), P<0.001. Median FU 13.9 mo.
    DeLLphi-305
    10 details 1 trial watching
    Design

    Phase 3, open-label, multicenter, randomized 1:1, N=563. OS interim analysis at 243 events (61% IF), two-sided boundary 0.008. Data cutoff 7 Jul 2026.

    Population & inclusion

    ES-SCLC after 4 cycles platinum-etoposide + durvalumab induction with no disease progression, ECOG PS 0-1, age ≥18. Asymptomatic untreated or treated brain mets allowed.

    Regimen

    Tarlatamab 10 mg Q2W + durvalumab 1500 mg Q4W vs durvalumab 1500 mg Q4W alone, 28-day cycles, until progression or toxicity. On-site monitoring 1-2h (6-8h in some regions) after early tarlatamab doses.

    Endpoints

    Primary: OS. Key secondary: PFS. Secondary: ORR, DOR, safety. Tested hierarchically OS → PFS → ORR.

    Results

    mOS 21.1 vs 12.7 mo, HR 0.42 (0.32-0.54), P<0.001; PFS 7.4 vs 1.9 mo, HR 0.34 (0.28-0.42); ORR 26% vs 4%.

    EndpointTarlatamab + durvalumabDurvalumabEffect
    Median PFS7.4 mo1.9 moHR 0.34 (0.28-0.42), P<0.001
    ORR26%4%n/a
    vs leading data

    Control arm is the current chemo-IO maintenance standard established by CASPIAN-era durvalumab, so the comparator is contemporary. Tarlatamab previously moved into later lines (DeLLphi-304); this trial tests it earlier, in the maintenance window.

    Applies to
    ES-SCLC nonprogressors after platinum-etoposide + durvalumab, ECOG 0-1
    Does not represent pts who progressed on induction, ECOG ≥2, or atezolizumab-based induction.
    Limitations

    Efficacy stop at 61% IF risks an inflated HR; median FU ~16 mo leaves the OS tail unknown. No safety data in source, and thoracic RT/PCI permissibility not stated.

    Discussion

    A BiTE added at the point of maximal disease control nearly halves the death hazard over durvalumab alone. Unsettled: toxicity cost, durability beyond the interim, and integration with consolidative RT.

    Enrolment
    CONSORT flow
    Randomized563
    ↓
    Tarlatamab + durvalumab
    allocated 282
    mOS 21.1 mo
    Durvalumab
    allocated 281
    mOS 12.7 mo
    Rationale

    Randomized phase 3, OS primary met at prespecified interim boundary, labeled primary analysis; source calls it a game-changer. Safety data absent from source.

    Open questions
    • Role of consolidative thoracic RT alongside tarlatamab maintenance
    • OS durability with follow-up beyond the interim analysis
    • Benefit and safety in pts with brain metastases
      recruiting Tarlatamab for SCLC Brain Metastases Phase 2
      n=35 · primary completion 2029-02 · ph2 tarlatamab intracranial efficacy, active SCLC brain mets

    Sourced from @_ShankarSiva

    📚 Sources · 🐦 1 tweet

    Systemic Palliative Phase 3 RCT Practice-changing ESMO Congress 2026

    Caveats dominate

    SBRT for Ultra-Central Lung Tumors Meta-Analysis

    ForUltra-central lung tumors (primary NSCLC or mets), PTV abutting/overlapping PBT

    TL;DRPooled 1-yr LC 92% and 2-yr LC 89% after ultra-central lung SBRT; G5 toxicity 4%, mostly hemoptysis, across 27 mostly retrospective studies.

    Why it mattersRadiation oncology

    The toxicity signal follows PBT hot spots, not the prescription: HILUS's 15% G5 came with a 67% IDL and median main bronchus Dmax 97 Gy. ISRS response: prescribe to 80-85% IDL, cap PBT Dmax at 133-150 Gy BED3 (EQD23 80-90 Gy), undercover PTV before overdosing airway.

    Monday clinic

    In an ultra-central lung tumor without endobronchial extension or ILD, this supports 60 Gy/8 or 60 Gy/15 with a strict PBT hot-spot limit; it does not extend to endobronchial disease, where ISRS favors 60 Gy/15 with PBT Dmax <100 Gy BED3. The longer read

    14 details 4 trials watching
    Design

    Systematic review and meta-analysis (PRISMA/MOOSE) of 27 studies, 1183 pts, published 2010-2022; random-effects pooling with meta-regression. All retrospective except HILUS (prospective phase II); none randomized. Median f/u ranged 7.6-44.5 mo.

    Population & inclusion

    Ultra-central lung tumors treated with SBRT (≥5 Gy/fx, photons), ≥5 eligible lesions per study. Excluded reirradiation and hilar/mediastinal nodal targets. Histology mixed; 9 studies (33%) were entirely primary NSCLC.

    Radiotherapy

    Dose 30-70 Gy in 3-10 fx, most often 50 Gy/5, 60 Gy/8, 60 Gy/12. Motion management in 96% of studies, mostly 4DCT. OAR dosimetry reporting was variable.

    Results

    1-yr LC 92% (95% CI 86-96), 2-yr LC 89% (82-94); primary NSCLC subset 95% at both timepoints. Higher BED tracked with 1-yr LC (HR 2.14, p=0.03), not 2-yr (p=0.66).

    EndpointPooled95% CIRangeI²
    1-yr LC (21 studies)92%86-9654-100%93.2%
    2-yr LC (19 studies)89%82-9457-100%94.3%
    Any G3-4 toxicity6%3-100-35%71%
    Any G5 toxicity4%2-60-22%68%
    G5 hemoptysis1%0-30-15%65%
    G3-4 pneumonitis1%0-20-11%5%
    CategoryRecommendation
    Delivery/dosing60 Gy/8 or 60 Gy/15; prescribe to 80-85% IDL; global Dmax far <150%
    PBT constraintDmax <133-150 Gy BED3 (EQD23 <80-90 Gy); lower if risk factors or near trachea/main bronchi
    Antiplatelet/anticoagulationHold when pausing is low-risk; else de-escalate PBT Dmax or use non-SBRT schedule
    Targeted/IOGap 2-3 days targeted, 3-4 wk VEGF inhibitors, ≥2 days IO
    Endobronchial tumorNon-SBRT (60 Gy/15); PBT Dmax <100 Gy BED3 (EQD23 <60 Gy)
    ILDLung V20 <10% strict cutoff; treat on trial
    Safety

    Any G3-4 6% (3-10), any G5 4% (2-6), G5 hemoptysis 1% (0-3). G5 ≥10% in 7 studies; HILUS 15%. Risk factors: endobronchial tumor, antiplatelet/anticoagulant use, VEGF inhibitor within 30 days (HR 16.9), ILD.

    vs leading data

    Pooled 2-yr LC sits beside RTOG 0813 (89.4% in central/UC tumors). A prior 250-pt systematic review reported higher toxicity (treatment-related mortality 5%, G≥3 10%); the authors attribute the lower rates here to more contemporary, conformal series.

    Applies to
    ultra-central primary NSCLC and lung metastases with PTV overlap of the PBT, treated with BED10-oriented SBRT and motion management
    Does not represent endobronchial tumors, ILD, hilar/mediastinal nodal targets, or reirradiation.
    Limitations

    Fig 3 dose-event mapping drew on only 37 events from 9 studies, and PBT substructure dosimetry was rarely reported, so constraints beyond HILUS's could not be derived. Toxicity attribution in retrospective series is open to misclassification.

    Discussion

    Efficacy is not the question; airway dose is. The ISRS constraint (PBT Dmax <133-150 Gy BED3) is built from cross-series convergence of fatal-hemoptysis doses, not a modeled threshold, and is pending SUNSET and LUNGTECH.

    Rationale

    Pooled retrospective series (one prospective, none randomized) with I² >90% for LC, publication bias on every endpoint, and inconsistent ultra-central definitions. Guideline layer is expert opinion.

    Open questions

    Sourced from Yan, Michael et al.

    📚 Sources · 📄 1 paper
    📄 PAPER Yan, Michael; Louie, Alexander V.; Kotecha, Rupesh et al. · Lung Cancer (2023-08)
    Stereotactic body radiotherapy for Ultra-Central lung Tumors: A systematic review and Meta-Analysis and International Stereotactic Radiosurgery Society practice guidelines
    doi

    Radiation Meta-analysis Caveats dominate

    Prostate

    ARPI intensification on top of local therapy is the theme: darolutamide with RT + ADT (DASL-HiCaP), apalutamide around RP (PROTEUS), abiraterone with ADT+docetaxel (PEACE-1).

    Confirmatory

    PEACE-1

    ForMetastatic prostate cancer on ADT+docetaxel, high or low volume

    TL;DRmOS 6.2 vs 4.4y (HR 0.68) adding abiraterone to ADT+docetaxel at 8y FU, n=710; no treatment-by-volume interaction (P=0.5552).

    Why it mattersRadiation oncology

    Low volume is where prostate RT sits, and abiraterone still more than doubled 7-yr rPFS there (43.4% vs 20.9%, HR 0.54) with no volume interaction (p=0.5552). Models adjusted for prostate RT, but an abiraterone-by-RT interaction is not reported in source, so this does not settle whether triplet and prostate RT add independently.

    Monday clinic

    In metastatic prostate cancer starting ADT+docetaxel, this supports abiraterone intensification in both high- and low-volume disease; it does not address pts not receiving docetaxel. The longer read

    PEACE-1
    VolumeMedian OS, y (Abi vs SOC)7-yr OS % (Abi vs SOC)Adj HR (95.1% CI)p
    High4.6 vs 3.540.9 vs 22.40.67 (0.54-0.85)0.0007
    Low7.8 vs 6.254.2 vs 46.00.74 (0.51-1.05)0.091
    +1 more figure
    PEACE-1
    VolumeMedian rPFS, y (Abi vs SOC)7-yr rPFS % (Abi vs SOC)Adj HR (99.9% CI)p
    High3.2 vs 1.533.4 vs 10.90.50 (0.35-0.73)<0.0001
    Low5.9 vs 2.743.4 vs 20.90.54 (0.32-0.91)<0.0001
    10 details
    Design

    Randomized trial, 8y FU long-term analysis presented at ESMO (Madrid). This report is restricted to the ADT+docetaxel population (n=710), split by metastatic extent.

    Population & inclusion

    High volume: n=224 Abi vs n=231 SOC. Low volume: n=131 Abi vs n=124 SOC.

    Regimen

    SOC (ADT+docetaxel, ± prostate RT) with vs without abiraterone. Dose and schedule not reported in source.

    Radiotherapy

    Prostate RT was a factor within SOC ("+/- RXT"); Cox models adjusted for prostate RT. RT dose, fractionation and the abiraterone effect within each RT stratum are not reported in source.

    Results

    Pooled OS benefit holds at 8y; volume-specific OS and rPFS are in the figure tables. No treatment-by-volume interaction (p=0.5552).

    EndpointTriplet (+Abi)DoubletEffect
    Median OS6.2 y4.4 yHR 0.68
    8-yr OS40.3%27.1%n/r
    vs leading data

    Extends the earlier PEACE-1 triplet result with longer follow-up and sits alongside ARASENS as the second ARPI + docetaxel triplet dataset. No cross-trial figures in source.

    Applies to
    pts with metastatic prostate cancer receiving ADT+docetaxel, high or low volume
    Does not represent pts treated without docetaxel.
    Limitations

    Low-volume OS rests on 67 vs 60 events with CI 0.51-1.05. Post-progression therapy, abiraterone exposure and safety at 8y are not reported in source.

    Discussion

    The absence of interaction argues against restricting the triplet to high-volume disease, even though low-volume OS has not cleared significance on its own. The rPFS signal in low volume is as large as in high volume, so the OS gap more likely reflects event count and the longer natural history of low-volume disease.

    Rationale

    Randomized long-term update in the docetaxel population, direction unchanged. Volume subgroups underpowered for OS (low-volume CI crosses 1), but no interaction supports a uniform effect.

    Open questions
    • Is abiraterone benefit independent of concurrent prostate RT?
    • Will low-volume OS benefit reach significance with more events?
    • Abiraterone vs darolutamide as the triplet partner

    Sourced from @mjuanfi81

    📚 Sources · 🐦 1 tweet

    Systemic Palliative Confirmatory

    STAMPEDE, ENZARAD, PROTEUS and DASL in context

    TL;DRESMO26 round-up of four intensification trials. STAMPEDE Decipher update suggests differential abiraterone benefit in cN0 disease (interaction P=.01).

    Trials discussed

    STAMPEDEENZARADPROTEUSDASL

    Why it mattersRadiation oncology

    The RT-relevant read is that STAMPEDE's abiraterone benefit was reported as predominantly in pts receiving RT, and the ESMO26 Decipher data suggest the abiraterone benefit differs in cN0 disease (interaction P=.01). Subgroup HRs are not reported in source text, so this flags, rather than settles, genomic selection of who gets abiraterone added to RT.

    Also covered Jul 15

    7 details
    Methods
    • 🔍 Trade-press-style round-up tweet placing STAMPEDE, ENZARAD, PROTEUS and DASL against #ESMO26 updates
    • 🔍 Disease state and RT dose/fractionation not stated in source
    Results
    • 📊 STAMPEDE: abiraterone-based intensification improved MFS and OS, predominantly with RT, per source
    • 📊 New #ESMO26 Decipher data: differential abiraterone benefit in cN0 disease, interaction P=.01
    Critique
    • ⚠️ No effect size reported in source tweet for MFS, OS, or the Decipher subgroups
    • ⚠️ Decipher interaction is a biomarker subgroup analysis; hypothesis-generating until validated
    • ⚠️ Tweet is truncated; ENZARAD, PROTEUS and DASL updates are not described in the source text
    Open questions
    • Does Decipher score select cN0 pts for abiraterone with RT?
    • Where do ENZARAD, PROTEUS and DASL fit relative to STAMPEDE?

    Sourced from @HimanshuNagarMD

    📚 Sources · 🐦 1 tweet

    Combined Curative ESMO Congress 2026

    Early signal

    DASL-HiCaP NCT04135353

    ForVery high-risk or N1 prostate, radical or early salvage RT + 2y ADT

    Metastasis-free survival (conventional imaging, MFS-CI) surrogate

    HR 0.42

    95% CI 0.27-0.66, p=0.0001; 4-yr MFS-CI 95% vs 88%

    TL;DR4-yr MFS-CI 95% vs 88%, HR 0.42, adding darolutamide to prostate/bed + pelvic LN RT and 96 wk ADT in very high-risk prostate cancer.

    Why it mattersRadiation oncology

    Every metastasis-free survival (MFS) difference comes from metastases (9 vs 46). Deaths without prior metastases were 18 vs 17. Both arms got prostate/bed plus pelvic nodal RT with 96 wk ADT, so this is darolutamide on top of an already intensified RT backbone, in both radical and salvage settings. RT dose was not reported.

    Monday clinic

    For a very high-risk patient (GG5, GG4 with adverse T stage or PSA, or cN1/pN1) planned for pelvic nodal RT with 2y ADT, this supports discussing darolutamide intensification. It does not extend to shorter ADT courses or to RT without nodal coverage. The longer read

    DASL-HiCaP
    MFS-CIRT + ADT + Darolutamide N=553RT + ADT + Placebo N=553
    Events, n (%)27 (5%)63 (11%)
    4-yr MFS-CI95%88%
    Metastases9 (33%)46 (73%)
    Death (w/o prior metastases)18 (67%)17 (27%)
    HR (95% CI), p0.42 (0.27-0.66), p=0.0001ref
    +2 more figures
    DASL-HiCaP
    Secondary endpoint (interim)HR (95% CI)
    PSA-PFS0.47 (0.33-0.67)
    CRPC0.22 (0.09-0.52)
    Subsequent hormonal therapy0.36 (0.21-0.60)
    PCSS0.58 (0.17-1.97)
    OS0.88 (0.49-1.59)
    Schema: 1,106 participants, R 1:1. Darolutamide 600 mg twice daily x 96 weeks vs placebo, both with RT + 96 weeks of ADT.
    Schema: 1,106 participants, R 1:1. Darolutamide 600 mg twice daily x 96 weeks vs placebo, both with RT + 96 weeks of ADT.
    9 details
    Design

    International, randomized, placebo-controlled phase 3, 1:1, N=1,106. Enrolment April 2020 to August 2023. Interim analysis triggered at the 87th MFS-CI event (67%); final analysis planned at 130 events.

    Population & inclusion

    DASL very high-risk pts getting radical RT (ISUP GG5, GG4 with cT2b-T4 / rT3a-T4 / PSA >20 ng/mL, or cN1) or salvage RT for PSA persistence or rise ≥0.1 ng/mL within 12 mo with pN1/cN1, GG5, or GG4 pT3a-pT4. Stratified by prior RP, planned docetaxel, pelvic N1.

    Regimen

    Darolutamide 600 mg BID x 96 wk vs placebo. Both arms got 96 wk ADT. Docetaxel use was allowed as a stratification factor.

    Radiotherapy

    Both arms: prostate/bed + pelvic LNs. Dose, fractionation and imaging used for staging are not reported in the source.

    Endpoints

    Primary: MFS by conventional imaging (MFS-CI). Secondary: OS, PCSS, PSA-PFS, time to subsequent hormonal therapy, time to castration resistance, AEs, HRQoL.

    Results

    Primary met at interim, HR 0.42 (0.27-0.66), p=0.0001, against a rejection boundary of 0.012. Authors report the benefit was consistent across all subgroups (no subgroup HRs in source).

    Safety

    Authors describe the treatment burden as similar to placebo. No AE rates or grade breakdown in source.

    vs leading data

    This sits alongside ENZARAD and the STAMPEDE M0 abiraterone work, which ask the same ARPI-plus-RT intensification question. DASL-HiCaP is the placebo-controlled test, it mandates pelvic nodal RT in both arms, and it includes an early-salvage cohort.

    Applies to
    DASL very high-risk pts getting radical or early salvage RT to the prostate/bed and pelvic nodes with 2y ADT
    Does not represent pts treated without pelvic nodal RT, with shorter ADT, or with metastatic disease on conventional imaging.
    Limitations

    Event-driven interim with only 27 vs 63 events, so the estimate may shrink by the final analysis. MFS is read on conventional imaging, which may not match PSMA-staged practice. Primary vs salvage results are not shown separately.

    Discussion

    The drug's effect is on metastases, not competing mortality, which supports a real anticancer benefit. Whether it becomes an OS benefit at PCSS HR 0.58 and OS HR 0.88 is still unknown.

    Enrolment
    CONSORT flow
    Randomized1106
    ↓
    RT + ADT + Darolutamide
    allocated 553
    4yr MFS-CI 95%
    RT + ADT + Placebo
    allocated 553
    4yr MFS-CI 88%
    Rationale

    Clean placebo-controlled phase 3, but this is the interim analysis (87/130 events). MFS is a surrogate and OS is immature. The prespecified final analysis is the gate.

    Open questions
    • Does the MFS benefit translate to OS at final analysis?
    • Is benefit similar in salvage vs radical RT cohorts?
    • Does the effect hold in PSMA-PET staged pts?

    Sourced from @alantanmd

    📚 Sources · 🐦 1 tweet

    Systemic Curative Phase 3 RCT Early signal ESMO Congress 2026

    Caveats dominate

    PROTEUS Substudy

    ForHR LPC/LAPC, conventionally staged M0, planned RP + PLND

    Event-free survival surrogate

    HR 0.38

    95% CI 0.26-0.55, p<0.0001

    TL;DREFS HR 0.38 (95% CI 0.26-0.55) with perioperative apalutamide + ADT around RP + PLND in HR LPC/LAPC; MFS HR 0.49, nominal p only.

    Why it mattersRadiation oncology

    The testosterone curve is the hidden read: T recovery to ≥200 ng/dL took a median 20.7 mo (~9 mo from EOT), so much of the EFS window is BCF assessed under residual castration. TTST medians of 46.0 vs 12.3 mo carry ~20 mo of lead-time, which leaves the durable-benefit question with MFS and its nominal p=0.0193.

    Monday clinic

    In conventionally staged HR LPC/LAPC headed for RP + PLND, this supports perioperative APA + ADT as an EFS-delaying option under discussion; it does not extend to PSMA PET-staged pts or to men treated with definitive RT. The longer read

    Also covered Aug 29 May 31

    PROTEUS Substudy
    ArmMedianRate (95% CI)
    APA + ADTNot reached63.0% (52.2-71.9)
    RP + PLND alone19.1 months41.4% (35.6-47.1)
    HR 0.38 (95% CI 0.26-0.55)p<0.0001n/a
    +3 more figures
    PROTEUS Substudy
    Metastasis detection method, n (%)APA + ADTRP + PLND
    PSMA PET9 (8.8)50 (16.3)
    Conventional imaging1 (1.0)6 (2.0)
    MFS HR 0.49 (95% CI 0.26-0.90)nominal p=0.0193n/a
    PROTEUS Substudy
    ArmMedian time to first subsequent therapy
    APA + ADT46.0 months
    RP + PLND alone12.3 months
    HR 0.29 (95% CI 0.20-0.43), nominal p<0.0001n/a
    PROTEUS Substudy
    11 details 1 trial watching
    Design

    Randomized 1:3, open-label, N=408, accrual July 2022 to October 2023. Stratified by cN0 vs cN1, Gleason 7 vs 8-10, and region. Phase not stated in source.

    Population & inclusion

    HR LPC/LAPC, conventionally staged M0 (CT + bone scan). No baseline PSMA PET.

    Regimen

    APA 240 mg QD + ADT for 6 cycles neoadjuvant, RP + PLND, then 6 cycles adjuvant. Control: RP + PLND with local or systemic adjuvant tx at physician discretion.

    Endpoints

    Primary: EFS, time to first BCF (PSA progression), LRR, DM or death. Secondary/exploratory: MFS, time to first subsequent therapy.

    Results

    EFS HR 0.38 (0.26-0.55), p<0.0001; MFS HR 0.49 (0.26-0.90), nominal p=0.0193; TTST HR 0.29 (0.20-0.43), nominal. Per-arm values in the figure captions.

    vs leading data

    proPSMA showed PSMA PET staging accuracy of 92% vs 65% for CT + bone scan, and EAU/ESMO advise PSMA PET/CT for high-risk disease where available. PROTEUS staged without it, so its M0 population differs from a modern PSMA-staged cohort.

    Applies to
    conventionally staged M0 HR LPC/LAPC treated with RP + PLND
    Does not represent PSMA PET-staged pts or men treated with definitive RT.
    Limitations

    1:3 allocation leaves 102 pts in the experimental arm. The control adjuvant strategy was at physician discretion, so the comparator is heterogeneous. Safety magnitudes were truncated in the source.

    Discussion

    Lead-time from treatment exposure and slow testosterone recovery inflate the early-window endpoints. Whether metastatic progression is truly delayed, rather than PSMA-avid disease being detected later, is not settled without baseline PSMA PET.

    Enrolment
    CONSORT flow
    Randomized408
    ↓
    APA + ADT + RP + PLND
    allocated 102
    EFS median not reached
    RP + PLND alone
    allocated 306
    EFS median 19.1 months
    Rationale

    Randomized, EFS met, but EFS leans on PSA failure during slow testosterone recovery; MFS nominal and PSMA-detection driven; TTST lead-time biased; no baseline PSMA PET.

    Open questions

    Sourced from @zklaassen_md, @alantanmd

    📚 Sources · 🐦 2 tweets

    Combined Curative Caveats dominate ESMO Congress 2026

    Lymphoma

    Early signal

    Low-Dose Involved Field RT in Indolent Lymphomas

    ForRecurrent symptomatic indolent B-cell lymphoma (mostly FL G1-2), pretreated

    TL;DR4 Gy involved-field RT in recurrent indolent lymphoma: ORR 92%, CR 61%, median time to local progression 25 mo, toxicity virtually absent.

    Why it mattersRadiation oncology

    The dose is the read: 2×2 Gy produced CR 61% with near-zero toxicity, and the 41 selected responders re-treated reached RR 98%, so the field can be re-irradiated. CR pts held local control for a median 42 mo, while PR pts progressed in-field at 10 mo, which frames 4 Gy as palliation that is durable mainly when it achieves CR.

    Monday clinic

    In a pretreated pt with recurrent symptomatic FL grade 1-2, this supports 4 Gy involved-field RT as a low-toxicity palliative option, repeatable on response; it does not address transformed disease or curative-intent early-stage FL. The longer read

    14 details 2 trials watching
    Design

    Phase II protocol, single cohort, N=109 assessable of 111 treated, 304 irradiated sites. Response assessed 4-6 wk post-RT then every 3 mo; median follow-up for pts in remission 7 mo.

    Population & inclusion

    Symptomatic recurrent B-cell indolent lymphoma; proven transformation and concurrent steroids or chemo excluded. Median age 62, median 2 prior regimens (range 0-11), bulky disease in 52% of pts with size data.

    Radiotherapy

    4 Gy as 2×2 Gy 48h apart (n=80) or 1×4 Gy (n=29), megavoltage photons or electrons. Target was the entire nodal area or the node with a 1.5 cm margin, involved sites only; 6 pts had total nodal irradiation.

    Endpoints

    in-field lymphoma control, response defined by local activity only, worst site counted. Secondary: TP (any progression) and TLP (in-field), Kaplan-Meier from first RT day.

    Results

    ORR 92%, CR 61%, PR 31%. Median TP 14 mo, TLP 25 mo; CR pts TLP 42 mo. Re-treatment in 41 selected responders: RR 98%, CR 71%.

    Response groupMedian TPMedian TLP
    All (n=109)14 mo25 mo
    CR (n=67)25 mo42 mo
    PR (n=34)9 mo10 mo
    Nonresponders2 mo2 mo
    Safety

    Toxicity virtually absent: one transient alopecia, one transient hyperpigmentation. Antiemetics for upper abdominal fields; allopurinol for bulky disease, no gout or tumor lysis.

    vs leading data

    Concordant with Girinsky et al (135 sites, 48 pts) on RR, CR and inferior bulky-site results, but 2yr local PFS in PR pts 46% there vs 10% here. FORT later tested this low-dose approach against conventional-dose RT in a randomized design.

    Applies to
    pretreated pts with recurrent symptomatic FL grade 1-2 and other indolent B-cell histologies
    Does not represent transformed disease, FL grade 3, or untreated early-stage FL.
    Limitations

    Comparison with pts' own prior regimens is historical and confounded by line of therapy, with power falling as numbers drop. Prognostic CR signals (≤2 sites P=.01, ≤5 cm P=.006) sit amid many tests; mixed target-volume definitions left to physician discretion.

    Discussion

    A local, repeatable, near-toxicity-free option for systemic disease, with response rates matching first-line systemic therapy in this cohort. It does not settle whether 4 Gy matches conventional dose for durability, particularly in PR or bulky sites.

    Rationale

    Single-cohort phase II, no randomized comparator vs conventional-dose RT or systemic therapy; within-patient historical comparison, 7-mo median follow-up in remitters.

    Open questions

    Sourced from Haas, R.L.M. et al.

    📚 Sources · 📄 1 paper
    📄 PAPER Haas, R.L.M.; Poortmans, Ph.; de Jong, D. et al. · Journal of Clinical Oncology (2003-07)
    High Response Rates and Lasting Remissions After Low-Dose Involved Field Radiotherapy in Indolent Lymphomas
    doi
    Abstract
    Purpose: To study the response rates and duration of response after low-dose (4 Gy) involved field radiotherapy (LD-IF-RT) in patients with recurrent indolent lymphoma. Patients and Methods: A total of 109 assessable patients (304 symptomatic sites) were irradiated (53 males and 56 females; median age, 62 years; range, 35 to 93), including 98 patients with follicular lymphoma (43 grade 1 and 55 grade 2), nine extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue-type and two patients with lymphoplasmacytoid lymphoma. Bulky disease (≥5 cm) was present in 52% of all patients. A median of two prior regimens (range, 0 to 11) preceded LD-IF-RT. The median time since diagnosis was 41 months (range, 2 to 358 months). Time to (local) progression was calculated according to the Kaplan-Meier method. Differences in response rates between treatments within the same patient were compared using the McNemar test. Results: The overall response rate was 92%; complete response was reached in 67 patients (61%), partial response in 34 patients (31%), stable disease in six patients (6%), and progressive disease in two patients (2%). The median time to progression was 14 months. The median time to local progression was 25 months. The 67 patients with complete response showed a median time to progression of 25 months and a median time to local progression of 42 months. None of the factors studied (age, sex, follicular lymphoma grade, radiotherapy regimen, number of previous regimens and previous history, number of positive sites or largest lymphoma diameter) were found to be related to response rate. Conclusion: LD-IF-RT is a valuable asset in the management of patients with follicular lymphoma and should be considered in patients with recurrent disease.

    Radiation Palliative Phase 2 trial Early signal

    Supportive / QoL

    Nonspine bone met SBRT: a randomized phase 2 favoring single-fraction SBRT, plus an expert survey with 35 Gy/5 the most chosen schedule.

    Consensus

    Nonspine Bone Metastases SBRT Practice Patterns

    ForNonsurgical nonspine bone metastases considered for SBRT

    TL;DR35 Gy/5 most often chosen (29/99 responses); 40 Gy/5 acceptable to 8 or 9 of 9 experts wherever listed; every schedule BED ≤100 Gy10.

    Why it mattersRadiation oncology

    The site-specific rejections are the RT read: 20 Gy/1 lost majority support in the humerus, acetabulum and femur cases, and 50 Gy/5 in the humerus and acetabulum, while 40 Gy/5 stayed acceptable to 8 or 9 of 9 wherever listed. For weight-bearing or periarticular targets, that favors moderate 5-fraction schedules over single fraction.

    Monday clinic

    For a nonsurgical nonspine bone met irradiated >3 months ago, this survey supports dose de-escalation (all 9 experts after prior SBRT, 7 of 9 after prior cRT); it does not address spine targets or postoperative bone. The longer read

    14 details
    Design

    Two-round survey of 9 international radiation oncologists chosen for NSBM-SBRT expertise, covering 11 cases with planning CT, MRI and GTV contours supplied. Round 2 rated each proposed schedule acceptable / not recommended / no opinion and picked 2 preferred schedules; majority defined as ≥5 of 9. Completion was 100%.

    Population & inclusion

    Nonsurgical nonspine bone metastases across long bones, pelvis and thorax, with RCC, breast, NSCLC and prostate primaries; some cases carried an extraosseous component.

    Radiotherapy

    6 experts prescribed one dose volume, 3 used an SIB with GTV/CTV or nested CTV1/CTV2 volumes. Schedules spanned 18-24 Gy/1 to 42-50 Gy/10, all at BED ≤100 Gy10.

    Results

    35 Gy/5 was chosen most (29 of 99 responses), and 40 Gy/5 was the most widely accepted. Scapula was the only case where every schedule had majority acceptance. Humerus, acetabulum and femur were the only cases where a majority rejected one or more schedules.

    ScheduleBED (Gy10)Use
    35 Gy/560Most common: 29 of 99 responses (29%); 5 experts in ≥1 case
    20 Gy/160≥3 experts
    30 Gy/360≥3 experts
    30 Gy/548≥3 experts
    CaseNot recommended by majority
    Humerus (RCC)20 Gy/1 · 50 Gy/5
    Acetabulum (breast)20 Gy/1 · 50 Gy/5 · 8 Gy/1 + 18 Gy/1 SIB
    Femur (NSCLC)20 Gy/1
    vs leading data

    The ≤100 Gy10 ceiling sits below the BED >100 Gy10 recommended for lung and liver SBRT. The cited Erler series reported LC 95% and 87% at 6 and 24 mo after 30-35 Gy/5, with 8.5% fracture at a median 2.5 mo; a second series of 85 NSBM reported 1-yr LC 92%.

    Applies to
    nonsurgical nonspine bone metastases treated with SBRT by experienced centers
    Does not represent spine SBRT, postoperative bone, or settings where OAR constraints force de-escalation.
    Limitations

    BED equivalence assumes α/β 10 across histologies, which the authors concede may not hold for breast and prostate. Health-system and resource differences across the panel may drive part of the variation attributed to judgment.

    Discussion

    The heterogeneity is real but bounded: a moderate-BED, 5-fraction working range emerges, and caution concentrates on weight-bearing long bones and joints. The optimal dose balancing LC and fracture stays unknown, and the authors call for phase I dose-finding and comparative trials.

    Rationale

    Expert practice survey (n=9) with acceptability ratings; no formal consensus process and no clinical outcomes, so it maps opinion rather than testing efficacy.

    Open questions
    • Upper dose threshold balancing LC and fracture in NSBM-SBRT
    • Predictors of fracture after nonspine bone SBRT
    • Toxicity profile of salvage NSBM-SBRT reirradiation

    Sourced from Nguyen, Timothy K. et al.

    📚 Sources · 📄 1 paper
    📄 PAPER Nguyen, Timothy K.; Sahgal, Arjun; Dagan, Roi et al. · Practical Radiation Oncology (2020-11)
    Stereotactic Body Radiation Therapy for Nonspine Bone Metastases: International Practice Patterns to Guide Treatment Planning
    doi

    Radiation Consensus

    Early signal

    Single-Fraction SBRT vs Multifraction RT for Nonspine Bone Metastases NCT02163226

    ForPainful, predominantly nonspine bone mets, life expectancy >3 mo, no prior RT

    TL;DR3-mo ITT pain response 38% vs 21% (P=.05) with 12-16 Gy single-fraction SBRT vs 30 Gy/10; 2-yr local PFS 100% vs 75.6%.

    Why it mattersRadiation oncology

    Dose, not single fraction per se, carries the pain signal: 3-mo ITT response was 62% (13 of 21) with 16 Gy vs 30% (18 of 60) with 12 Gy, and 12 Gy tracked 30 Gy/10 at 9 mo (13.3% vs 15.2%). Because 16 Gy went to smaller lesions, the dose choice remains hypothesis-level.

    Monday clinic

    In a pt with a painful nonspine bone met, good performance status and longer expected survival, this supports single-fraction SBRT as a reasonable alternative to 30 Gy/10; it does not test SBRT against an 8 Gy single fraction or extend to spine lesions, cord compression or pathologic fracture. The longer read

    14 details 2 trials watching
    Design

    Phase 2, nonblinded, randomized noninferiority trial at one institution, 1:1, N=160 (81 SBRT, 79 MFRT). Stratified by tumor size, bone site and number of sites irradiated. Enrolled September 2014 to June 2018.

    Population & inclusion

    Pathologic cancer diagnosis, painful bone mets (score ≥2 of 10), age ≥18, life expectancy >3 mo; up to 3 fields allowed. Excluded prior RT to the site, untreated cord compression, pathologic fracture at the site, and recent radioisotope.

    Radiotherapy

    SBRT 12 or 16 Gy x1 by lesion size (4 cm cutoff) vs 30 Gy in 10 fx. PTV = GTV + 5 mm, no CTV; 2D/3D, IMRT or VMAT delivery. Prophylactic 7-day low-dose dexamethasone recommended for SBRT only.

    Endpoints

    Primary: pain response by international consensus criteria (pain score plus MED), noninferiority margin 10%. Secondary: MDASI QoL, CTCAE toxicity, local control, OS.

    Safety

    No toxicity differences between arms. G3 fatigue 9.9% vs 5.1% (P=.37), fracture 1.2% vs 0% (P=.99); MDASI scores improved in both arms without a difference.

    vs leading data

    Prior randomized trials found no pain difference between single and multifraction conventional courses, with more retreatment after 8 Gy. RTOG 9714 and the Dutch Bone Metastasis Study are the conventional-dose trials behind that equivalence. This trial escalates the single fraction but never tests it against 8 Gy.

    Applies to
    pts with painful, predominantly nonspine bone mets, good expected survival and no prior RT to the site
    Does not represent spine lesions, cord compression, pathologic fracture, or the 8 Gy single-fraction decision.
    Limitations

    Dexamethasone given asymmetrically to SBRT pts confounds early pain response. The 16 vs 12 Gy contrast is non-randomized and tracks lesion size. Five SBRT pts did not receive treatment due to insurance denial, and median OS of 6.7 mo leaves few pts at risk for late local failure.

    Discussion

    The ITT data support noninferiority and a local-control advantage for SBRT; the superiority read depends on per-protocol denominators. The live question is 16 Gy vs 8 Gy in pts selected for longer survival, which needs a phase 3.

    Results
    Analysis · timepointSBRTMFRTP
    ITT · 1 mo44% (n=36)30% (n=24).18
    ITT · 3 mo38% (n=31)21% (n=17).05
    Per-protocol · 2 wk34 of 55 (62%)19 of 52 (36%).01
    Per-protocol · 3 mo31 of 43 (72%)17 of 35 (49%).03
    Per-protocol · 9 mo17 of 22 (77%)12 of 26 (46%).04
    Timepoint16 Gy x112 Gy x130 Gy/10P
    3 mo62% (13 of 21)30% (18 of 60)21% (17 of 79).003
    9 mo42.9% (9 of 21)13.3% (8 of 60)15.2% (12 of 79).005
    EndpointSBRTMFRTP
    1-yr local PFS100%90.5%.01 (curve)
    2-yr local PFS100%75.6%.01 (curve)
    24-mo cumulative local failure0%9.7%.02
    2-yr reirradiation0%5.3%.10
    Enrolment
    CONSORT flow
    Randomized160
    ↓
    Single-fraction SBRT
    allocated 81
    analyzed 81
    3-mo pain response 38%
    MFRT 30 Gy/10
    allocated 79
    analyzed 79
    3-mo pain response 21%
    Rationale

    Single-institution randomized phase 2 with one-sided alpha 0.20; superiority signals are per-protocol amid heavy attrition, comparator 30 Gy/10 rather than 8 Gy. Authors call for phase 3.

    Open questions

    Sourced from Nguyen, Quynh-Nhu et al.

    📚 Sources · 📄 1 paper
    📄 PAPER Nguyen, Quynh-Nhu; Chun, Stephen G.; Chow, Edward et al. · JAMA Oncology (2019-06)
    Single-Fraction Stereotactic vs Conventional Multifraction Radiotherapy for Pain Relief in Patients With Predominantly Nonspine Bone Metastases
    doi

    Radiation Palliative Phase 2 trial Early signal