onc brain

About ยท curated by Nick Boehling, MD ยท @nb2276

2026-05-20

digest generated 2026-06-27

LS-SCLC 54Gy twice-daily SIB beats 45Gy: mOS 60.7 vs 39.5mo (HR 0.55, p=0.003), though early-stopped and single-country (N=224).
Thoracic carried the day: a Chinese phase 3 escalating the twice-daily LS-SCLC schedule to 54Gy nearly doubled mOS (60.7 vs 39.5mo), though early stopping and modest N temper it. Breast offered a proton trade-off, higher capsular contracture vs photon PMRT, but the signal washed out on multivariable adjustment.

Breast

Proton PMRT's cardiac/pulmonary dosimetry edge may carry a capsular-contracture cost, though the association attenuates to NS after multivariable adjustment.

Proton vs Photon PMRT and Capsular Contracture

ForPost-mastectomy breast cancer, implant reconstruction, receiving PMRT

TL;DRCC risk HR 2.3 (1.26-4.30) for proton vs photon PMRT univariately, NS on multivariable (1.76, p=.083).

Why it mattersRadiation oncology

The proton signal concentrates in DTI reconstruction (50% vs 35% photon 2yr CC); on multivariable the proton HR falls to 1.76 (p=.083) while DTI itself carries HR 3.0, so reconstruction type, not beam, may drive most of the risk. For protons' cardiopulmonary dosimetric edge, this argues for staged TE/I over DTI when CC risk weighs on the choice.

vs leading data
  • Proton PMRT adopted for better cardiac/pulmonary dosimetry; CC may be the trade-off

Radiation Curative Retrospective Caveats dominate

8 details 3 trials watching
  • ๐Ÿ” Retrospective, 2 centers within single institution, N=175 (89 proton, 86 photon), treated 2017-2023
  • ๐Ÿ” Median f/u 42mo proton vs 47mo photon; median age 49, 63% Hispanic
  • ๐Ÿ” All TE/I pts had the tissue expander irradiated
  • ๐Ÿ“Š 1ยฐ comparison: proton vs photon capsular contracture. Univariate HR 2.3 (95% CI 1.26-4.30), p=.007
  • ๐Ÿ“ Multivariable: proton HR 1.76 (0.93-3.32), p=.083; attenuates to non-significant after adjustment
  • ๐Ÿ“Š Strongest predictor on MVA: DTI vs TE/I reconstruction, HR 3.0 (1.7-5.5), p<.001
  • ๐Ÿ“Š 2-year CC rate by modality ร— reconstruction (p<.001 across groups)
    ReconstructionProtonPhoton
    DTI50% (n=36)35% (n=15)
    TE/I23% (n=53)12% (n=71)
  • โš ๏ธ Groups imbalanced: tumor laterality (p<.001) and reconstruction type (p<.001), residual confounding likely

Sourced from Zerey et al., Zerey, M.M. et al.

๐Ÿ“š Sources ยท ๐Ÿ“„ 2 papers
๐Ÿ“„ PAPER Zerey; Gal; Feenstra et al. ยท 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.
๐Ÿ“„ PAPER Zerey, M.M.; Gal, O.; Feenstra, N. et al. ยท 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?
๐Ÿ“ https://doi.org/10.1016/j.ijrobp.2025.07.1298

Thoracic / Lung

First positive dose-escalation signal for the twice-daily LS-SCLC schedule itself (GTV boost to 54Gy), where CONVERT's once-daily escalation was null.

LS-SCLC High-Dose Hyperfractionated RT (54 Gy vs 45 Gy) Phase 3 NCT03214003

ForLimited-stage SCLC, ECOG 0-1, age 18-70, untreated or 1 prior chemo cycle

TL;DRmOS 60.7 vs 39.5mo, HR 0.55 (0.37-0.72), p=0.003 favoring 54Gy twice-daily SIB over 45Gy in LS-SCLC.

Why it mattersRadiation oncology

The transferable detail: the 54Gy boost hit only the GTV, the PTV stayed at 45Gy/30fx, so G3-4 oesophagitis (13 vs 12%) and pneumonitis (5 vs 6%) held flat despite the mOS jump to 60.7 vs 39.5mo. The lever here is SIB dose-escalation of the twice-daily schedule, not once-daily escalation.

vs leading data
  • Standard LS-SCLC RT is 45Gy twice-daily (Turrisi, NEJM 1999); CONVERT found no OS gain from once-daily dose escalation. This escalates the twice-daily schedule itself to 54Gy

Radiation Curative Phase 3 RCT Challenges SOC

8 details 2 trials watching
  • ๐Ÿ” Phase 3 open-label RCT, 16 Chinese sites, N=224 (54Gy 108 / 45Gy 116); median f/u 46mo
  • ๐Ÿ” SIB technique: 54Gy/30fx boost to GTV only; PTV held at 45Gy/30fx in both arms
  • ๐Ÿ” Both arms accelerated twice-daily VMAT, 10fx/week, concurrent platinum-etoposide; PCI 25Gy/10fx for responders
CONSORT flow
Assessed / enrolled 224
โ†“
Randomized 224
โ†“
54 Gy SIB
allocated 108
45 Gy
allocated 116
  • ๐Ÿ“Š 1ยฐ EP OS (ITT): mOS 60.7mo (95% CI 49.2-62.0) with 54Gy vs 39.5mo (27.5-51.4) with 45Gy
  • ๐Ÿ“ OS HR 0.55 (95% CI 0.37-0.72), p=0.003
  • ๐Ÿ“Š G3-4 radiotherapy toxicity by arm โ€” comparison values omitted (cell value "0.84" not verified in source)
  • โš ๏ธ DSMB-terminated early (Apr 2021) for sufficient benefit; early stopping can overestimate effect size
  • โš ๏ธ Open-label, modest N=224, single-country (China); the unusually large OS gain warrants Western confirmation

Sourced from Jiayi Yu et al.

๐Ÿ“š Sources ยท ๐Ÿ“„ 1 paper
๐Ÿ“„ PAPER Jiayi Yu; Leilei Jiang; Lina Zhao et al. ยท 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