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About · curated by Nick Boehling, MD · @nb2276

    Real-world evidence

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    ctDNA surveillance in non-operative rectal cancer management

    ForStage I-III MSS rectal, cCR/nCR after NAT, undergoing NOM

    TL;DRctDNA sensitivity only 41% for local regrowth vs 74% for distant mets in 110 NOM rectal pts; risk stratifies but cannot replace imaging.

    Curative Real-world evidence Early signal

    ctDNA surveillance in non-operative rectal cancer management
    OutcomeSensitivitySpecificityAccuracy
    Local regrowth12/29 (41%)480/509 (94%)492/538 (91%)
    Distant metastasis31/42 (74%)611/627 (97%)642/669 (96%)
    7 details
    Methods
    • 🔍 N=110, INTERCEPT program, MD Anderson 2020-2024; stage I-III MSS rectal adenocarcinoma, cCR/nCR after NAT → NOM; Signatera™ tumor-informed ctDNA
    • 🔍 22/23 pts with local regrowth underwent salvage surgery; ctDNA-positive at regrowth: ypT3-4 75% vs 21% (ctDNA-negative), p=0.01
    Results
    • 📊 Ever-positive longitudinal ctDNA: worse 2-yr local regrowth-free survival (log-rank p=0.0002) and metastasis-free survival (p<0.0001)
    • 📊 First post-NAT ctDNA positive (within 180 days): worse regrowth-free (p=0.0006) and metastasis-free survival (p<0.0001)
    • 📊 Positive ctDNA associated with regrowth (~60%) and distant mets (~60%) in ctDNA-positive pts
    Critique
    • ⚠️ Sensitivity only 41% for local regrowth — negative ctDNA does not exclude local recurrence; endoscopy and MRI remain essential
    • ⚠️ Single-institution non-randomised cohort, N=110, median f/u 25 months; no ctDNA-guided vs standard surveillance arm
    Open questions
    • Does ctDNA-guided intensified surveillance improve salvage surgery success rates?
    • Optimal ctDNA testing frequency and timing within NOM protocols
    • Performance in dMMR/MSI-H pts (all MSS here)
    📚 Sources · 🐦 1 tweet

    DBCG IMN2 NCT06549920

    ForNode-positive breast cancer, adjuvant RT, taxane/trastuzumab/AI systemic therapy

    TL;DR15-yr OS 65.0% vs 60.8%, HR 0.85 (0.76-0.94), p=0.0016 favoring IMNI in node-positive breast cancer with modern systemic therapy, N=4541.

    vs leading data
    • vs DBCG IMN1 (N=3089, 2003-07): OS gain 4.7% at 14.8-yr f/u; confirms benefit persists in modern era
    • vs KROG 06-08 (negative Korean study, 3D-RT + newer agents): IMN2 contradicts null result

    Radiation Curative Real-world evidence Confirmatory

    8 details
    Methods
    • 🔍 Prospective nationwide cohort, N=4541, Jan 2007-May 2014; median f/u 13.7 yr
    • 🔍 Allocation: right-sided → IMNI, left-sided → no IMNI; 6 RT centres, 3D-based RT
    • 🔍 Systemic: taxane-based chemo, AIs, trastuzumab
    Results
    • 📊 Primary EP OS: 15-yr 65.0% (IMNI) vs 60.8% (no IMNI)
    • 📊 All endpoints favor IMNI (adjusted HRs)
      EndpointHR (95% CI)p
      OS0.85 (0.76-0.94)0.0016
      Breast cancer mortality0.84 (0.74-0.95)0.0077
      Distant metastasis0.87 (0.78-0.98)0.026
    Critique
    • ⚠️ Cohort design, not RCT; laterality-based allocation; baseline characteristics balanced but not randomized
    • ⚠️ No subgroup identified favoring IMNI omission, including 1-3 positive axillary nodes
    Notes
    • Cardiac: 15-yr ischemic/valvular HD death
      • 0.2% (95% CI 0.0-0.5) right-sided / IMNI
      • 0.7% (95% CI 0.4-1.2) left-sided / no IMNI
      • Gap likely reflects left breast cardiac dose, not IMNI-specific toxicity
    Open questions
    • Benefit with post-2014 systemic agents (CDK4/6i, T-DM1) not established
    • Optimal IMNI technique to minimize cardiac exposure in left-sided pts
    • Whether cohort evidence sufficient to shift 1-3 node guidelines broadly
    📚 Sources · 📄 1 paper
    📄 PAPER Anders W. Mølby Nielsen; Lise B. J. Thorsen; Demet Özcan et al. · The Lancet Regional Health - Europe (2025-02)
    Internal mammary node irradiation in 4541 node-positive breast cancer patients treated with newer systemic therapies and 3D-based radiotherapy (DBCG IMN2): a prospective, nationwide, population-based cohort study
    PMID → doi
    Abstract
    Background Internal mammary node irradiation (IMNI) improves overall survival (OS) in node-positive breast cancer patients. However, the effect is not documented in breast cancer patients treated with newer systemic therapies and 3D-based radiotherapy (RT). Therefore, the Danish Breast Cancer Group (DBCG) IMN2 study aimed to investigate the effect of IMNI in node-positive breast cancer patients treated with newer systemic therapies and 3D-based RT.<br/>Methods DBCG IMN2 was a nationwide population-based cohort study prospectively allocating node-positive breast cancer patients with right-sided tumours to IMNI and patients with left-sided tumours to no IMNI in six RT centres. Exclusion criteria were prior malignancies, bilateral breast cancer, neoadjuvant systemic therapy, recurrence before RT, or non-standard RT. Systemic treatment included taxane-based chemotherapy, aromatase inhibitors, and trastuzumab. The primary end-point was OS. Secondary endpoints were breast cancer mortality and distant metastasis. Cox regression analyses were used for adjusted hazard ratios (HR). Clinicaltrial.gov ID: NCT06549920.<br/>Findings In the period January 2007–May 2014, a total of 4541 patients were included. Patient characteristics were distributed evenly between right- and left-sided patients. Median follow-up was 13.7 years for OS. Survival rates at 15 years were 65.0% in patients with IMNI and 60.8% without leading to an adjusted HR of 0.85 (95% CI, 0.76–0.94; p = 0.0016) for OS. Corresponding HRs were 0.84 (95% CI, 0.74–0.95; p = 0.0077) for breast cancer mortality and HR 0.87 (95% CI, 0.78–0.98; p = 0.026) for distant metastasis. No subgroups were identified for the omission of IMNI. The 15-year cumulative incidence of death from ischemic or valvular heart disease was 0.2% (95% CI, 0.0–0.5) in right-sided and 0.7% (95% CI, 0.4–1.2) in left-sided patients.<br/>Interpretation IMNI reduced distant metastasis and breast cancer mortality and improved OS in node-positive breast cancer patients, despite treatment with newer systemic therapies and 3D-based RT.

    Dutch BCRG Breast Boost (Modern Systemic Era)

    ForEarly-stage breast cancer, BCT + WBRT, modern systemic therapy era, stratified b

    TL;DR10-yr IBTR 1.2% with or without boost in 0-2 risk-factor BCT pts; boost omission appears safe in modern systemic era.

    vs leading data
    • vs EORTC 22881/10882 (Bartelink, Lancet Oncol 2015): boost reduced IBTR ~50% in pre-modern-systemic era; absolute benefit appears negligible for 0-2 rf pts now

    Radiation Curative Real-world evidence Early signal

    Dutch BCRG Breast Boost (Modern Systemic Era)
    Risk factors5yr IBTR (no boost)5yr IBTR (boost)10yr IBTR (no boost)10yr IBTR (boost)
    0-2 (N=15,085/13,845)0.6%0.7%1.2%1.2%
    ≥3 (N=149/733)1.3%2.9%2.7%3.3%
    Uncertain (N=592/944)0.8%3.3%1.4%3.6%
    +1 more figure
    Dutch BCRG Breast Boost (Modern Systemic Era)
    5 details
    Methods
    • 🔍 Dutch registry retrospective cohort, BCT pts 2012-2016; boost vs no-boost allocation was clinical, non-randomized
    • 🔍 Five risk factors scored: age ≤40, grade 3, TNBC, inadequate guideline-directed systemic therapy, no pCR post-NACT in TNBC/HER2+
      • 0-2 rf: large majority (n=15,085 no boost, n=13,845 boost)
      • ≥3 rf: small high-risk minority (n=149 no boost, n=733 boost)
    Results
    • 📊 Assisi decision thresholds: boost omissible if 10yr IBTR <3% (boosted cohort) or <6% (no-boost); only boosted ≥3-rf pts exceeded threshold at 10yr (3.3%)
    Critique
    • ⚠️ Non-randomized; no-boost selection reflects clinician risk stratification, not random allocation; confounding by indication expected
    • ⚠️ No-boost arm for ≥3 rf pts very small (n=149); insufficient to characterize boost omission in high-risk subgroup
    Open questions
    • RCT needed to confirm boost omission equivalence in 0-2 risk-factor pts
    • Optimal RT boost strategy for ≥3 risk-factor pts where boosted 10yr IBTR still exceeds Assisi threshold
    📚 Sources · 🐦 1 tweet

    OligoCare

    ForOligometastatic solid tumors, multiple histologies, 1-5 mets, SABR-eligible

    TL;DR88.6% local control at 3yrs across 2447 pts; CRC shows worst local control despite highest delivered dose.

    vs leading data
    • Adds real-world multi-institutional scale to phase II RCT signals (SABR-COMET, STOMP, ORIOLE); direction consistent

    Radiation Real-world evidence Early signal

    OligoCare
    Tumor type1-yr local failure3-yr local failure
    CRC9.3%19.6%
    Breast4.1%11.3%
    NSCLC6.0%9.8%
    Prostate2.7%8.1%
    +2 more figures
    Overall local in-field progression: 5.0% at 1yr, 11.4% at 3yrs. N=2447, median f/u 31 months.
    Overall local in-field progression: 5.0% at 1yr, 11.4% at 3yrs. N=2447, median f/u 31 months.
    OligoCare
    7 details
    Methods
    • 🔍 Prospective multi-institutional EORTC registry (OligoCare), 57 sites; interim analysis
    • 🔍 2447 pts, 3533 lesions; median age 69 (range 28-94), 69% male; median f/u 31 months
    Results
    • 📊 88.6% local control at 3yrs
    • 📊 Minimum PTV dose: most critical technical factor for local control
    Critique
    • ⚠️ De novo OMD better LC than repeat OMD (attributed to higher delivered dose in de novo setting)
    • ⚠️ CRC worst LC despite highest median dose per fraction; relative radioresistance; combination treatment or dose escalation strategies may be needed
    • ⚠️ Single-arm interim registry; no comparator; histology mix and 6-yr enrollment window limit subgroup inference
    Open questions
    • Optimal approach for CRC oligomets (combination treatment, dose escalation?)
    • Minimum PTV dose thresholds for adequate LC across histologies
    • Whether LC advantage for de novo vs repeat OMD reflects dose, biology, or selection
    📚 Sources · 🐦 1 tweet