onc brain

About · curated by Nick Boehling, MD · @nb2276

    Challenges SOC

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    ESAONA

    For1L EGFR-mutated NSCLC with active brain metastases

    TL;DRIntracranial ORR 95.5% vs 79.6% (p=0.0004), iPFS HR 0.46 favoring asandeutertinib over osimertinib in 1L EGFR+ NSCLC with brain mets.

    vs leading data
    • Osimertinib established 1L SOC via FLAURA; ESAONA is first randomized head-to-head with a next-gen EGFR TKI in the brain-met-enriched setting

    Systemic Palliative Phase 2 trial Challenges SOC

    ESAONA
    EndpointAsandeutertinibOsimertinibHR / p
    iORR (BICR)95.5% (89.8-98.5%)79.6% (71.0-86.6%)p=0.0004
    Intracranial PFSNR17.5 mo (15.18-NA)HR 0.46, p=0.0020
    Overall PFSNR17.2 mo (15.18-19.55)HR 0.64, p=0.0473
    5 details
    Methods
    • 🔍 Phase II, randomized, N=224; 1L EGFR-mutated NSCLC with brain mets, asandeutertinib (n=111) vs osimertinib (n=113)
    • 💊 Asandeutertinib: next-generation EGFR TKI evaluated head-to-head vs established osimertinib SOC
    CONSORT flow
    Randomized 224
    ↓
    Asandeutertinib
    allocated 111
    Osimertinib
    allocated 113
    Critique
    • ⚠️ Safety (TRAEs)
      • Any TRAEs: 99.1% (asandeutertinib) vs 95.6% (osimertinib)
      • Serious TRAEs: 10.8% vs 7.1% — slightly higher in experimental arm
    • ⚠️ Phase 2 only, N=224; PFS medians not reached in experimental arm (immature); OS data not reported in source
    • ⚠️ Primary EP was iORR (response endpoint), not PFS or OS; longer follow-up required for survival readout
    Open questions
    • Phase 3 OS confirmatory data needed before practice adoption
    • Activity after progression on prior osimertinib unknown
    • Optimal sequencing vs osimertinib + chemo (FLAURA2) in brain-met population
    📚 Sources · 🐦 1 tweet

    Wait or Treat — NCT05236946 (Upfront vs Delayed Brain RT in Oncogene-mutated NSCLC) NCT05236946

    ForMetastatic NSCLC, EGFR or ALK mutant, completely asymptomatic BM, ECOG 0-2

    TL;DRUpfront brain RT halves icPD (HR 0.35, p<0.001) but OS numerically favors delayed (HR 1.45, 2yr 60% vs 48%) in EGFR/ALK+ mNSCLC.

    vs leading data
    • First RCT on this question; supports emerging TKI-first approach (osimertinib/alectinib CNS penetration)

    Radiation Palliative Phase 3 RCT Challenges SOC

    Wait or Treat — NCT05236946 (Upfront vs Delayed Brain RT in Oncogene-mutated NSCLC)
    Upfront RT (n=105)Delayed RT (n=103)
    Events2047
    1-yr cumulative icPD8.7% (2.9%, 14.5%)25.7% (16.8%, 34.7%)
    2-yr cumulative icPD21.7% (12.6%, 30.8%)50% (39.2%, 60.9%)
    Sub-HR (95% CI)0.35 (0.21, 0.59)ref
    p-value<0.001—
    +1 more figure
    Wait or Treat — NCT05236946 (Upfront vs Delayed Brain RT in Oncogene-mutated NSCLC)
    7 details
    Methods
    • 🔍 Phase III open-label RCT, N=208; EGFR/ALK+ mNSCLC, completely asymptomatic BM, ECOG 0-2
    • 🔍 Both arms: TKIs + chemotherapy; delayed arm: RT at intracranial PD or patient request
    • 🔍 Stratification: GPA score (0-2 vs >2); synchronous vs metachronous BM
    CONSORT flow
    Randomized 208
    ↓
    Upfront Cranial RT
    allocated 105
    Delayed Cranial RT
    allocated 103
    Results
    • 📊 OS HR 1.45 favoring delayed; 2yr OS 48% upfront vs 60% delayed (secondary endpoint)
    Critique
    • ⚠️ Radiation necrosis: 6% upfront vs 0% delayed
    • ⚠️ OS HR p-value not reported in source; trial takeaway: 'timing of RT does not affect survival'
    • ⚠️ TKI + chemo backbone may not reflect current osimertinib or alectinib monotherapy practice
    Open questions
    • Does icPD reduction with upfront RT translate to QoL or neurocognitive benefit?
    • SRS vs WBRT in upfront arm: impact on radiation necrosis rate?
    • Which pts (high GPA, many lesions) benefit most from upfront cranial RT?
    📚 Sources · 🐦 3 tweets

    EORTC 22922/10925

    ForStage I-III breast, node-positive or central/medial tumor, median age 54, post-s

    TL;DR20yr OS HR 1.00 (null): BC mortality reduced HR 0.82 but non-BC deaths increased HR 1.26, offsetting benefit.

    vs leading data
    • vs EORTC 22922 10yr data (NEJM 2015): DFS and BC mortality benefit seen at 10yr did not translate to OS by 20yr; competing-cause mortality dominant

    Radiation Curative Phase 3 RCT Challenges SOC

    6 details
    Methods
    • 🔍 Phase 3 RCT, N=4004 randomized 1996-2004, median f/u 22.2yr; prespecified 20yr final analysis
    • 🔍 Eligible: women ≤75yr, stage I-III, node-positive OR central/medial tumor; post-mastectomy or BCS + ALND
    Results
    • 📊 Outcomes at 20 years (IM-MS-RT vs control)
      EndpointControlIM-MS-RTHRp
      OS (20yr rate)61.8%61.0%1.00.967
      DFS (20yr rate)49.0%48.2%0.97.515
      DMFS (20yr rate)59.8%58.9%0.97.578
      BC mortality (20yr rate)22.4%18.6%0.82.006
      Non-BC deaths (20yr rate)15.8%20.4%1.26.002
    Critique
    • ⚠️ Non-BC death excess emerged after 15yr, driven by cardiac and pulmonary morbidity from IM-MS-RT
    • ⚠️ Late RT morbidity (IM-MS-RT vs control)
      • Lung fibrosis: 6.3% vs 3.2%
      • Cardiac fibrosis: 2.7% vs 1.7%
      • Cardiac diseases: 15.2% vs 11.7%
      • Severe cardiac G3-4: 1.9% vs 1.7%
      • Severe lung G3-4: 0.3% vs 0.0%
    • ⚠️ 2D RT planning era (enrolled 1996-2004); modern cardiac-sparing techniques may attenuate the non-BC mortality signal
    Open questions
    • Does modern cardiac-sparing IM-RT eliminate the non-BC death excess?
    • Which subgroups (high nodal burden, HER2+, TNBC) derive net OS benefit?
    • Impact of contemporary systemic therapy on IM-MS-RT benefit/harm ratio
    📚 Sources · 📄 1 paper
    📄 PAPER Kaidar‐Person, Orit; Weltens, Caroline G.; Fortpied, Catherine et al. · CA: A Cancer Journal for Clinicians (2026-05)
    Twenty‐year results of the randomized European Organization for Research and Treatment of Cancer trial 22922/10925 evaluating internal mammary chain and medial supraclavicular lymph node irradiation in stage I–III breast cancer
    PMID → doi
    Abstract
    Abstract European Organization for Research and Treatment of Cancer trial EORTC 22922/10925 evaluated internal mammary and medial supraclavicular (IM‐MS) lymph node irradiation (IM‐MS‐RT) in patients with stage I–III breast cancer. Eligible patients had involved axillary nodes and/or centrally/medially located tumors regardless of nodal involvement. The primary end point was overall survival, secondary end points were disease‐free survival, distant metastases‐free survival, breast cancer mortality, and any breast recurrence. Between 1996 and 2004, 4004 patients were randomized. The median patient age was 54 years. At a median follow‐up of 22.2 years, 1550 (38.7%) patients died, of whom 796 (51.4%) died from breast cancer. At 20 years, the overall survival rate was 61.8% in the control group versus 61.0% in the IM‐MS‐RT group (hazard ratio [HR], 1.00; p = .967); the disease‐free survival rate was 49.0% versus 48.2%, respectively (HR, 0.97; p = .515); and the distant metastases‐free survival rate was 59.8% versus 58.9%, respectively (HR, 0.97; p = .578). The breast cancer mortality rate was 22.4% in the control group and 18.6% in the IM‐MS‐RT group (HR, 0.82; p = .006), whereas the rate of deaths not from breast cancer or from unknown causes was 15.8% versus 20.4%, respectively (HR, 1.26; p = .002). Lung fibrosis, cardiac fibrosis, and cardiac diseases were more frequent after IM‐MS‐RT versus no IM‐MS‐RT (6.3% vs. 3.2%, 2.7% vs. 1.7%. and 15.2% vs. 11.7%, respectively); and the rates of severe cardiac and lung morbidities (scores of 3 or 4) were 1.9% versus 1.7% and 0.3% versus 0.0%, respectively. Breast cancer mortality at 20 years was statistically significantly lower after IM‐MS‐RT, but deaths not from breast cancer increased after 15 years, resulting in no long‐term benefit of IM‐MS‐RT on overall survival. Therefore, the authors strongly call for very long‐term follow‐up of treatments for prognostically favorable cancers such as breast cancer.

    LS-SCLC 54 Gy Hyperfractionated RT NCT03214003

    ForLS-SCLC, ECOG 0–1, age 18–70, chemo-naive or ≤1 prior platinum-etoposide cycle

    TL;DRmOS 60.7 vs 39.5mo (HR 0.55, p=0.003) favoring 54 Gy hyperfractionated RT in LS-SCLC; no added toxicity.

    vs leading data
    • vs CONVERT trial (Lancet Oncol 2017): CONVERT also BID 45 Gy SIB to 66 Gy failed to show OS benefit over 45 Gy — this trial's positive result contrasts CONVERT's null, likely due to SIB technique differences and PTV homogeneity approach

    Radiation Curative Phase 3 RCT Challenges SOC

    9 details
    Methods
    • 🔍 Phase 3 open-label RCT; N=224; 16 centers in China; 1:1 randomization; median f/u 46mo
    • 🔍 54 Gy SIB to GTV in 30 BID fractions vs 45 Gy in 30 BID fractions; both arms VMAT; PTV 45 Gy both arms
    • 🔍 Chemo-naive or ≤1 prior cisplatin/carboplatin+etoposide cycle; ECOG 0–1; age 18–70
    • 💊 Concurrent chemotherapy + PCI (25 Gy/10 fx) for responders in both arms
    CONSORT flow
    Assessed / enrolled 224
    ↓
    Randomized 224
    ↓
    54 Gy SIB
    allocated 108
    analyzed 108
    45 Gy
    allocated 116
    analyzed 116
    Results
    • 📊 1° EP (OS): mOS 60.7mo (95% CI 49.2–62.0) vs 39.5mo (27.5–51.4), HR 0.55 (0.37–0.72), p=0.003
    Critique
    • ⚠️ G3–4 RT toxicity by type
      • Oesophagitis: 13% (54 Gy) vs 12% (45 Gy), p=0.84
      • Pneumonitis: 5% (54 Gy) vs 6% (45 Gy), p=0.663
      • 1 treatment-related death in 54 Gy arm (MI)
    • ⚠️ Trial stopped early by DSMB (April 2021) on clinical benefit grounds; early termination inflates effect estimates
    • ⚠️ Single-country (China), age-capped at 70, open-label; generalizability to Western populations uncertain
    • ⚠️ 45 Gy BID (not OD) control — aligns with historical standard but not universally practiced globally
    Open questions
    • Confirmatory data needed in non-Asian populations
    • Optimal dose escalation with modern immunotherapy combinations
    • Late cardiac/pulmonary toxicity beyond 46mo median f/u
    📚 Sources · 📄 1 paper
    📄 PAPER Jiayi Yu; Leilei Jiang; Lina Zhao et al. · Lancet Respiratory Medicine (2024-08)
    High-dose hyperfractionated simultaneous integrated boost radiotherapy versus standard-dose radiotherapy for limited-stage small-cell lung cancer in China: a multicentre, open-label, randomised, phase 3 trial
    PMID → doi
    Abstract
    Background For the past 20 years, twice-daily thoracic radiotherapy with concurrent chemotherapy has been the treatment of choice for limited-stage small-cell lung cancer (LS-SCLC), which has a poor prognosis. We aimed to assess the efficacy and safety of high-dose, accelerated, hyperfractionated, twice-daily thoracic radiotherapy (54 Gy in 30 fractions) versus standard-dose radiotherapy (45 Gy in 30 fractions) as a first-line treatment for LS-SCLC.<br/>Methods This open-label, randomised, phase 3 trial was performed at 16 public hospitals in China. The key inclusion criteria were patients aged 18–70 years, with histologically or cytologically confirmed LS-SCLC, who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and who were previously untreated or had received one course of cisplatin or carboplatin and etoposide. Eligible patients were randomly assigned (1:1) to receive volumetric-modulated arc radiotherapy (VMAT) of 45 Gy in 30 fractions to the gross tumour volume or VMAT with a simultaneous integrated boost of 54 Gy in 30 fractions to the gross tumour volume starting 0–42 days after the first chemotherapy course. Both groups received 10 fractions of twice-daily thoracic radiotherapy per week. The planning target volume was 45 Gy in 30 fractions in both groups. Patients with responsive disease received prophylactic cranial radiotherapy (25 Gy in 10 fractions). Randomisation was performed using a centralised interactive web response system, stratified by ECOG performance status, disease stage, previous chemotherapy course, and chemotherapy choice. The primary outcome was overall survival in the intention-to-treat population. Safety was analysed in the as-treated population. This study was registered at ClinicalTrials.gov, NCT03214003.<br/>Findings From June 30, 2017, to April 6, 2021, 224 patients (102 [46%] females and 122 [54%] males; median age 64 years [IQR 58–68]) were enrolled and randomly assigned to the 54 Gy group (n=108) or 45 Gy (n=116) group. The median follow-up was 46 months (IQR 33–56). The median overall survival was significantly longer in the 54 Gy group (60·7 months [95% CI 49·2–62·0]) than in the 45 Gy group (39·5 months [27·5–51·4]; hazard ratio 0·55 [95% CI 0·37–0·72]; p=0·003). Treatment was tolerable, and the chemotherapy-related and radiotherapy-related toxicities were similar between the groups. The grade 3–4 radiotherapy toxicities were oesophagitis (14 [13%] of 108 patients in the 54 Gy group vs 14 [12%] of 116 patients in the 45 Gy group; p=0·84) and pneumonitis (five [5%] of 108 patients vs seven [6%] of 116 patients; p=0·663). Only one treatment-related death occurred in the 54 Gy group (myocardial infarction). The study was prematurely terminated by an independent data safety monitoring board on April 30, 2021, based on evidence of sufficient clinical benefit.<br/>Interpretation Compared with standard-dose thoracic radiotherapy (45 Gy), high-dose radiotherapy (54 Gy) improved overall survival without increasing toxicity in a cohort of patients aged 18–70 years with LS-SCLC. Our results support the use of twice-daily accelerated thoracic radiotherapy (54 Gy) with concurrent chemotherapy as an alternative first-line LS-SCLC treatment option.

    ePLND vs PSMA PET staging in prostate cancer (AUA 2026)

    ForLocalized prostate cancer, intermediate to high risk, primary staging pre-RP

    TL;DR47.7% of LN mets outside ePLND template; PSMA PET NPV ~96%; RCTs no consistent BCR benefit from routine dissection.

    vs leading data
    • Emerging: targeted/sentinel LND guided by PSMA PET-positive nodes vs full-template ePLND

    Surgery Curative Challenges SOC

    Yaxley et al. (BJUI 2019): 1253 men primary staging Ga-PSMA PET/CT; 47.7% of LN mets outside ePLND template.
    Yaxley et al. (BJUI 2019): 1253 men primary staging Ga-PSMA PET/CT; 47.7% of LN mets outside ePLND template.
    +2 more figures
    Lower limb lymphedema: RP+PLND 0-14%, pelvic LN RT 0-9%, PLND+salvage RT 19-29%; DVT/PE risk 6-10x with PLND (Tyritzis, n=3544).
    Lower limb lymphedema: RP+PLND 0-14%, pelvic LN RT 0-9%, PLND+salvage RT 19-29%; DVT/PE risk 6-10x with PLND (Tyritzis, n=3544).
    ePLND vs PSMA PET staging in prostate cancer (AUA 2026)
    7 details
    Methods
    • 🔍 Intermediate risk: PLND safely omittable if PSMA PET negative; missed LN likely small, equally missed by ePLND
    • 🔍 High-risk: individual decision; PSMA PET negative → consider post-op pelvic RT over ePLND to limit lymphedema
    Results
    • 📊 Yaxley et al. (BJUI 2019), n=1253: 47.7% of LN mets outside ePLND anatomic template
    • 📊 PSMA PET NPV ~96% for LNI at primary staging
    Critique
    • ⚠️ RCTs show no consistent BCR improvement attributable to routine ePLND
    • ⚠️ No Level 1 evidence for significant oncological benefit from ePLND (Roberts et al., PCAN 2024)
    • ⚠️ PLND morbidity (Clinckaert systematic review; Tyritzis J Urol 2015, n=3544)
      • Lower limb lymphedema: 0-14% RP+PLND; 0-9% pelvic LN RT; 19-29% PLND + salvage pelvic RT
      • DVT/PE risk 6-10x increased with PLND vs no PLND
    Open questions
    • Which high-risk pts still benefit from ePLND over PSMA PET-guided approach?
    • Role of targeted/sentinel LND using PSMA PET-positive nodes vs full-template ePLND
    • Long-term BCR/MFS outcomes when ePLND omitted based on negative PSMA PET
    📚 Sources · 🐦 1 tweet

    PEACE 2

    ForVHR localized prostate (≥2: Gleason ≥8, T3-T4, PSA ≥20), N0M0 on conventional im

    TL;DRPelvic RT did not improve cPFS vs prostate-only RT in VHR localized prostate cancer (HR 0.81, p=0.088).

    vs leading data
    • Contrasts with POP-RT, which showed bPFS and MFS benefit from pelvic RT in high-risk CaP; population definitions and staging modalities differ

    Radiation Curative Phase 3 RCT Challenges SOC

    PEACE 2
    Prostate-only RTPelvic RT
    7-yr cPFS62.9% [57.4; 68.1]67.1% [61.6; 72.2]
    HR (95% CI)ref0.81 [0.63; 1.03]
    p0.088
    +1 more figure
    PEACE 2
    8 details
    Methods
    • 🔍 Phase III, 4-arm: ADT × 3 yrs + prostate RT ± cabazitaxel × 4 cycles; pelvic vs prostate-only RT comparison
    • 🔍 VHR eligibility: ≥2 of Gleason ≥8, T3-T4, PSA ≥20 ng/mL; N0M0 on conventional imaging or choline PET/CT
    • 💊 Side effects minimal with modern RT techniques; no quantitative toxicity figures reported in source
    CONSORT flow
    Randomized 761
    ↓
    Prostate-only RT (A+C pooled)
    allocated 380
    Pelvic RT (B+D pooled)
    allocated 381
    Results
    • 📊 1° EP cPFS: HR 0.81 (95% CI 0.63-1.03), p=0.088 — non-significant
    • 📊 7-yr cPFS: 67.1% pelvic RT vs 62.9% prostate-only RT
    • 📊 No improvement on secondary endpoints: MFS, PCSS, OS (effect sizes not reported in source)
    Critique
    • ⚠️ Staged with conventional imaging/choline PET, not PSMA-PET; PSMA-era cohort may carry different nodal risk profile
    • ⚠️ Presenter conclusion: pelvic RT cannot be considered SOC even in pts at high nodal extension risk without detectable disease on imaging
    Open questions
    • Does PSMA-PET staging identify a nodal subgroup that benefits from pelvic RT?
    • How to reconcile with POP-RT (different risk definitions, staging modalities)?
    • Does cabazitaxel interaction modify pelvic RT benefit in the 4-arm design?
    📚 Sources · 🐦 1 tweet

    TORPEdO (CRUK/18/010)

    ForOropharyngeal SCC requiring definitive concurrent CRT with bilateral neck treatm

    TL;DRIMPT showed no HR-QoL benefit vs IMRT at 12 months in OPSCC; UW-QoL scores similar across arms to 24 months.

    vs leading data
    • Lancet 2026 (McBride et al.): concurrent proton vs photon analysis in OPSCC

    Radiation Curative Phase 3 RCT Challenges SOC

    TORPEdO (CRUK/18/010)
    +1 more figure
    Phase 3 RCT schema: IMPT vs IMRT 2:1; 205 pts; 70/56 Gy in 33 fractions; cisplatin 100mg/m² D1+D22
    Phase 3 RCT schema: IMPT vs IMRT 2:1; 205 pts; 70/56 Gy in 33 fractions; cisplatin 100mg/m² D1+D22
    7 details
    Methods
    • 🔍 Phase 3 RCT; N=205; 2:1 IMPT vs IMRT; cisplatin 100mg/m² D1+D22; 70/56 Gy in 33 fractions over 6.5 weeks
    • 🔍 HR-QoL declines at end of treatment then recovers; most pts stabilize by 12 months post-CRT
    Results
    • 📊 Patient-reported co-primary: UW-QoL physical composite (saliva, taste, chewing, swallowing, appearance, speech) at 12 months post-CRT
    • 📊 No differences in UW-QoL scores between arms at 3, 12, or 24 months post-RT
    • 📊 Clinician-reported co-primary (CTCAE G3 weight loss or gastrostomy dependence at 12 months): not reported in this presentation
    Critique
    • ⚠️ Meaningful HR-QoL deterioration persists in some pts up to 2 years in both arms
    • ⚠️ Commentary: identical planning constraints and novice UK proton centers likely attenuated any IMPT advantage; high-experience centers may still see clinical benefit
    Open questions
    • Does proton center experience modify HR-QoL or late-toxicity outcomes?
    • Will clinician-reported co-primary (G3 weight loss/gastrostomy) diverge from HR-QoL?
    • Late-effect differentiation at 5-year follow-up
    📚 Sources · 🐦 2 tweets · 📄 1 paper
    📄 PAPER McBride; Riaz; Sherman et al. · Lancet (London, England) (2026-05)
    Proton versus photon therapy for oropharyngeal cancer.
    PMID 42134353 → doi
    📝 McBride SM, Riaz N, Sherman EJ, Tsai CJ, Mell LK. Proton versus photon therapy for oropharyngeal cancer. Lancet. 2026 May 16;407(10542):1917.

    EORTC IM-MS (22922/10925)

    ForStage I-III BC, node-positive or pN0, adjuvant IM-MS RT decision

    TL;DR20-yr OS null (HR 1.00, p=0.967); BCM benefit offset by non-BCM excess; pN0: no benefit.

    vs leading data
    • DBCG IMN2 (Lancet Reg Health Eur 2024): modern IM-MS RT (MHD 1.2 Gy right / 2.3 Gy left) showed BCM + DM + OS benefit at 15yr in node-positive pts

    Radiation Curative Phase 3 RCT Challenges SOC

    EORTC IM-MS (22922/10925)
    Arm20-yr OSHR (95% CI)p
    +IM-MS RT61.0%1.00 (0.90-1.10)0.967
    -IM-MS RT61.8%——
    +3 more figures
    EORTC IM-MS (22922/10925)
    Endpoint (15yr)+IM-MS-IM-MSHR (95% CI)p
    BCM18.6%22.4%0.82 (0.72-0.95)0.006
    non-BCM20.4%15.8%1.26 (1.09-1.46)0.002
    EORTC IM-MS (22922/10925)
    Late AE (absolute rate)+IM-MS-IM-MS
    Lung fibrosis6.3%3.2%
    Cardiac fibrosis2.7%1.7%
    Cardiac diseases15.2%11.7%
    EORTC IM-MS (22922/10925)
    Endpoint (20yr, pN0)+IM-MS-IM-MSHR (95% CI)p
    DFS53.9%53.6%0.93 (0.81-1.07)0.318
    DMFS67.2%67.4%0.93 (0.78-1.10)0.397
    4 details
    Methods
    • 🔍 Phase III RCT, N=4004, stage I-III BC; IM + medial supraclavicular RT vs no IM-MS RT; 20-yr follow-up
    CONSORT flow
    Randomized 4004
    ↓
    +IM-MS RT
    allocated 2002
    -IM-MS RT
    allocated 2002
    Results
    • 📊 BCM reduction (HR 0.82, p=0.006 at 15yr) fully offset by non-BCM excess (HR 1.26, p=0.002); net OS nullified at 20yr
    Critique
    • ⚠️ pN0 subgroup: no DFS or DMFS benefit at 20yr; IM-MS benefit restricted to node-positive disease
    • ⚠️ EORTC era heart doses 4-9x higher than DBCG IMN2; late cardiac mortality likely drives the non-BCM excess at 20yr
    Open questions
    • Whether modern low-dose cardiac RT (DBCG IMN2) restores net OS benefit at 20yr
    • Which node-positive subgroup (pN1 vs pN2-3) retains net BCM benefit over late cardiotox
    • Should pN0 be excluded from IM-MS RT indications given consistently null data
    📚 Sources · 🐦 2 tweets

    DBCG RT Natural

    For≥60y, pT1N0, ER+ ≥10%, HER2-normal, grade 1-2, unifocal post-lumpectomy

    TL;DR9.8% 4-yr LR without PBI vs 1.5% with PBI in pT1N0 low-risk elderly breast conservation; stopped early per pre-specified threshold.

    vs leading data
    • PRIME II (Lancet Oncol 2015): ~10% 10-yr LR without RT in ≥65y low-risk ER+; RT benefit durable

    Radiation Curative Phase 3 RCT Challenges SOC

    DBCG RT Natural
    ArmEvents/TotalCIF % (95% CI)
    +RT2/2361.5 (0.3-5.1%)
    -RT19/2729.8 (5.9-14.9%)
    S-RT18/2788.2 (4.5-13.3%)
    +1 more figure
    DBCG RT Natural
    4 details
    Methods
    • 🔍 Phase III RCT; ≥60y, pT1N0, ER+ ≥10%, HER2-normal, grade 1-2, unifocal, non-lobular, margin ≥2mm, breast conservation
    • 🔍 RT arm: PBI 40Gy/15fr; ET per DBCG guideline (recommended pT1c and/or grade 2); stratified by institution + ET yes/no
    CONSORT flow
    Randomized 508
    ↓
    PBI 40Gy/15fr
    allocated 236
    No PBI
    allocated 272
    Critique
    • ⚠️ Median FU 4 yrs; primary endpoint is 5-yr invasive LR; stopped early per pre-specified 4% max-LR threshold
    • ⚠️ Suboptimal ET adherence per presenter; -ET groups drive high LR in the -RT arm; adherence confounds the no-treatment effect
    Open questions
    • Whether WBRT (vs PBI) changes the RT-omission picture in this population
    • Which molecular low-risk subset, if any, can safely defer all adjuvant therapy
    • Duration of ET benefit when combined with PBI in ≥60y low-risk pts
    📚 Sources · 🐦 2 tweets