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Retrospective

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NRG Clinico-Transcriptomic Risk Stratification (Abstract 5000)

ForNCCN β‰₯ high-risk localized prostate cancer, RT+ADT candidates

TL;DR22-gene GC independently predicts MFS, DM, and OS; combined NRG score reclassifies ~25% discordant NCCN high-risk pts for AAP intensification.

vs leading data
  • STAMPEDE MO calibration anchor (Attard, Lancet 2022): HRMFS 0.53 (95% CI 0.44-0.64), HROS 0.60 (0.48-0.73), both p < 0.0001 for AAP intensification

Radiation Curative Retrospective Early signal

NRG Clinico-Transcriptomic Risk Stratification (Abstract 5000)
+1 more figure
NRG Clinico-Transcriptomic Risk Stratification (Abstract 5000)
GC HighGC Low
Clinical High49%15%
Clinical Low9%27%
5 details
  • πŸ” Combined clinico-transcriptomic (CT) score: NCCN points + GC points
    • NCCN HR = 1 pt; NCCN VHR = 2 pts
    • GC <HR = 0 pt; GC HR = 1 pt; GC VHR = 2 pts
    • CT HR (≀2 pts) β†’ RT+ADT; CT VHR (β‰₯3 pts) β†’ RT+ADT+AAP
  • πŸ“Š 22-gene GC independently predicts MFS, DM, and OS beyond clinical variables alone (p < 0.001 for each endpoint)
  • πŸ“Š ~25% of NCCN β‰₯HR pts have discordant clinical vs. GC risk, warranting the combined approach
  • ⚠️ Framework developed on existing NRG trial data; no prospective RCT validating CT-score-guided treatment allocation reported
  • ⚠️ Design not fully specified in source; likely secondary correlative analysis; GC cutoffs extend Spratt et al. (JCO 2018) prior work
  • Prospective RCT: does CT-score-guided allocation improve outcomes vs. clinical risk alone?
  • Generalizability to modern ARSI-backbone ADT regimens
  • GC threshold stability across contemporary cohorts
πŸ“š Sources Β· 🐦 2 tweets

Proton vs Photon PMRT Capsular Contracture (Zerey et al.)

ForPost-mastectomy breast cancer, subpectoral TE/I or DTI reconstruction, PMRT cand

TL;DRMVA HR 1.76 (P=0.083) proton vs photon CC, non-significant; proton+DTI 2yr CC 50% vs photon+DTI 35%.

vs leading data
  • Proton PMRT improves cardiac/pulmonary dosimetry vs photon; this CC signal is the risk to weigh in reconstruction planning

Radiation Curative Retrospective Caveats dominate

8 details
  • πŸ” Retrospective, 2 centers/single institution, N=175 (89 proton, 86 photon), Jan 2017-Dec 2023; median f/u 42 vs 47 mo
  • πŸ“Š 2-year CC rates by modality and reconstruction type
    ReconstructionProtonPhoton
    DTI50%35%
    TE/I23%12%
  • πŸ“ MVA HR 1.76 (95% CI 0.93-3.32), P=0.083 for proton vs photon
  • πŸ“ Univariate HR 2.3 (95% CI 1.26-4.30), P=0.007 for proton vs photon
  • πŸ“ DTI vs TE/I in MVA: HR 3.0 (95% CI 1.7-5.5), P<.001
  • ⚠️ Groups unbalanced for reconstruction type (TE/I vs DTI, P<.001); this is the dominant confounder and MVA adjustment may be insufficient
  • ⚠️ Groups also unbalanced for tumor laterality (P<.001); uncontrolled institutional practice patterns, not randomization
  • ⚠️ MVA primary result is P=0.083, below conventional significance; framed as a trend, not a confirmed signal
  • Does proton-CC signal replicate in a prospective matched or randomized cohort?
  • Optimal reconstruction type (TE/I vs DTI) when proton PMRT is indicated for cardiac/pulmonary dosimetry reasons?
πŸ“š Sources Β· πŸ“„ 2 papers
πŸ“„ PAPER Zerey; Gal; Feenstra et al. Β· International journal of radiation oncology, biology, physics (2026-04)
Does Pencil Beam Scanning Proton Therapy Impart a Higher Risk of Capsular Contracture Compared With Intensity Modulated Photon Radiation Therapy in the Postmastectomy Reconstruction Setting?
Abstract
BACKGROUND: Postmastectomy radiation therapy (PMRT) may cause adverse events in the reconstruction setting. Proton-based PMRT is increasingly used and has been shown to improve cardiac and pulmonary dosimetry. Data on the risk of capsular contracture (CC) with proton versus photon PMRT remain scarce. We compared the CC rate of the largest cohort of patients undergoing reconstruction after pencil beam scanning proton PMRT reported to date with an intensity modulated radiation therapy photon cohort, hypothesizing that the proton cohort would have a higher rate of CC.<br/><br/>METHODS AND MATERIALS: An institutional review board -approved retrospective study was conducted on patients with breast cancer who underwent subpectoral 2-stage tissue expander/implant (TE/I) or direct-to-implant (DTI) breast reconstruction and received either pencil beam scanning proton or intensity modulated radiation therapy photon PMRT between January 2017 and December 2023 at 2 centers within a single institution. All patients undergoing TE/I had the TE irradiated. CC rates were estimated using the Kaplan-Meier method. Cox proportional hazards analysis, denoted as hazard ratios (HRs) with 95% CIs, was used to assess variables potentially associated with the outcome, and a binary logistic regression model was used to verify the results.<br/><br/>RESULTS: The study cohort comprised 175 patients (89 proton; 86 photon). The median age was 49 years (range, 24-78), 63% were Hispanic. Patient demographics were well balanced between the groups, except in tumor laterality (P < .001) and reconstruction type (TE/I vs DTI; P < .001). The median follow-up was 42 and 47 months for the proton and photon groups, respectively. In a multivariable analysis, DTI patients had a significantly higher risk of CC compared with TE/I patients (HR, 3.0; 95% CI, 1.7-5.5; P < .001). Proton patients had a higher risk of developing CC compared with the photon group in univariate analysis (HR, 2.3; 95% CI, 1.26-4.30; P = .007), although this effect did not reach statistical significance in the multivariable model (HR, 1.76; 95% CI, 0.93-3.32; P = .083). The 2-year CC rate for patients treated with protons and DTI (n = 36), photons and DTI (n = 15), protons and TE/I (n = 53), and photons and TE/I (n = 71) was 50%, 35%, 23%, 12%, respectively (P < .001). No other factors were significantly associated with CC development.<br/><br/>CONCLUSION: In this contemporary large proton versus photon PMRT cohort, patients treated with proton showed a trend toward an increased risk of CC. Patients undergoing DTI who were treated with protons had the highest risk of CC (50%). Careful consideration of reconstruction and radiation therapy modalities, assessing CC risk, and also involving patient input, is important for treatment selection.
πŸ“„ PAPER Zerey, M.M.; Gal, O.; Feenstra, N. et al. Β· International Journal of Radiation Oncology*Biology*Physics (2025-09)
Does Pencil Beam Scanning Proton Therapy Impart a Higher Risk of Capsular Contracture when Compared with Intensity Modulated Photon Radiotherapy in the Post-Mastectomy Reconstruction Setting?
πŸ“ https://doi.org/10.1016/j.ijrobp.2025.07.1298

Bladder-preserving TMT for MIBC: prognostic factors (ESTRO 2026)

ForcT2-T4aNOMO MIBC, median age 76, selected for organ-preserving TMT

TL;DRCLR 63.7% in 369 MIBC pts on TMT; 5-FU-based CRT (OR 4.9) and portal imaging frequency independently predicted CLR.

vs leading data
  • CLR 63.7% and salvage cystectomy 9.7% consistent with published international TMT series

Combined Curative Retrospective Confirmatory

Bladder-preserving TMT for MIBC: prognostic factors (ESTRO 2026)
8 details
  • πŸ” Multicenter retrospective cohort, Spain 2010-2022; N=369, median age 76, 85% male, cT2-T4aNOMO
  • πŸ” TMT = maximal TURBT + concurrent chemoradiotherapy; 1Β° EP: CLR; multivariable logistic regression
  • πŸ“Š CLR: 63.7%; salvage cystectomy: 9.7%
  • πŸ“Š Disease progression 28.8%: local 10.1%, systemic 10.7%, combined 8.7%
  • πŸ“Š CLR associated with lower local recurrence and better survival (no OS/CSS HR in source)
  • πŸ“ Independent predictors of CLR (multivariable)
    • 5-FU-based CRT β†’ higher CLR: OR 4.9 (95% CI 1.1-22.1), p=0.038
    • Weekly portal imaging β†’ lower CLR: OR 0.35 (95% CI 0.20-0.60), p<0.001
  • ⚠️ Retrospective, 12-yr accrual (2010-2022): era effects likely across RT technique and CRT regimen selection
  • ⚠️ Portal imaging OR 0.35 is counterintuitive; probably proxies older/less precise RT delivery, not a causal detriment
  • 5-FU vs gemcitabine vs other radiosensitizers: prospective CRT regimen comparison needed
  • Whether modern IGRT (VMAT, CBCT) improves CLR vs older portal imaging techniques
πŸ“š Sources Β· 🐦 1 tweet