onc brain

Cross-sectional cohort of 4908 breast cancer pts treated with 3D-CRT or IMRT from 2008 to 2018 at one Canadian tertiary center, 2223 left-sided in the primary analysis. Median follow-up 10.8 years (IQR 8.4-13.1). Dosimetry auto-segmented from planning CT, converted to EQD2; competing-risks (Fine and Gray) regression adjusted for cardiovascular risk factors.

Breast cancer treated with 3-dimensional conformal or intensity-modulated RT, 2008 to 2018, with the primary analysis restricted to left-sided disease. Systemic cardiotoxic exposure (anthracycline, trastuzumab) is not reported in source.

3D-CRT or IMRT across the heart-sparing era; LAD and heart automatically segmented and dose converted to EQD2. The threshold is a max point dose to the LAD, not a mean, and the reference schedules are moderate hypofractionation (42.5 Gy in 16 fx) and ultrahypofractionation (26 Gy in 5 fx).

Adverse cardiac events: MI, or admission / ED visit for unstable angina, arrhythmia, heart failure, pericarditis, myocarditis. Coronary angiography and revascularization captured separately as CAD. Discrimination compared by ROC C index, adjusted association by competing-risks regression.

10-year cumulative incidence of cardiac event or CAD was 5.0% (95% CI 4.1-6.0). Metric-by-metric comparison is in the table above.

Current whole-heart constraints descend from population dose-response work on cohorts irradiated when incidental cardiac exposure was far higher (Darby, NEJM 2013), the era in which mean heart dose had usable spread. This is the modern counterpart of those series, and the reversal it reports is what you would expect if heart-sparing planning compressed mean heart dose below its discriminating range. The referenced schedules, 42.5 Gy in 16 fractions and 26 Gy in 5 fractions (FAST-Forward), are current practice, so the dosimetric translation transfers.

The mean heart dose null is hard to separate from restricted range: a 2 Gy dichotomy inside a heart-sparing cohort may not span enough exposure for a gradient to show. The endpoint counts coronary angiography and revascularization, which track ascertainment and access as well as biology. Systemic cardiotoxic exposure is not reported in source, leaving an obvious confounder unaddressed.

The asymmetry that matters is cost: an LAD max objective plus breath-hold usually costs optimization time, not target coverage, so a weak association is enough to justify it, while it would not justify trading away chest wall or nodal coverage. The measurement problem cuts the other way, since a max point dose to a small mobile auto-segmented vessel is among the least reproducible quantities to write into a protocol. Motion management carries the least methodological baggage of the two recommendations: it lowers LAD dose and heart dose together.

Cross-sectional single-center cohort with a cut point derived in the same data; C index 0.58 barely above chance and its interval overlaps mean heart dose's.

Secondary pathological analysis of the ProtecT randomized trial (active monitoring vs radical prostatectomy vs EBRT with neoadjuvant ADT). Central review of biopsy slides retrieved for 712 of 1,643 randomized pts, with both intention-to-treat and per-protocol analyses, the latter accounting for crossover to radical treatment.

PSA-screened men with clinically localized prostate cancer, the original ProtecT eligibility. Slides were regraded under 2019 ISUP criteria rather than the trial-era 2005 criteria; the presenter reports regrading did not change the picture. Age, PSA and revised Gleason score did not differ significantly across arms in the reviewed subset.

The RT arm was external-beam radiotherapy with 3 to 6 months of neoadjuvant ADT. No dose, fractionation or target volume is given in the source. The presenter notes cribriform-positive disease was more prevalent in this arm, attributed to chance since cribriform status was not a randomization characteristic.

Primary: metastases at 15-year median follow-up, analysed by cribriform status. Multivariable Cox modelling was used to compare metastasis risk across grade groups within the cribriform-negative stratum.

Roughly 13% of the reviewed cohort was cribriform-positive. Among the 87% cribriform-negative, early radical treatment produced no statistically significant reduction in 15-year metastases vs active monitoring, in both ITT and per-protocol analyses. Cribriform-negative grade group 2 carried metastasis risk equivalent to grade group 1.

Slides were available for under half the randomized cohort, so the analysis rests on whichever centres have so far returned material. The source excerpt is a video interview that stops mid-presentation and reports no HRs, CIs or event counts, so the size of the null in the cribriform-negative group cannot be judged from it.

The interest here is the inverse of the usual cribriform argument. Rather than showing cribriform-positive pts do badly on surveillance, the useful signal is that cribriform-negative grade group 2 behaves like grade group 1 over 15 years, which is a de-escalation read. Whether the cribriform-positive stratum shows the reciprocal benefit is not in the source excerpt.

Post-hoc subgroup of a non-stratified variable in 712 of 1,643 pts, with a non-significant negative result and no effect sizes in the source.

IRB-approved retrospective cohort at 2 centers within one institution, PMRT delivered 2017-2023. N=175 (89 PBS proton, 86 IMRT photon). CC estimated by Kaplan-Meier, with Cox proportional hazards for covariates and a binary logistic model as verification.

Breast cancer pts who underwent subpectoral 2-stage TE/I or DTI reconstruction and then PMRT. Median age 49 (range 24-78), 63% Hispanic. Groups were balanced except on tumor laterality (P < .001) and reconstruction type (P < .001), the two axes the analysis turns on.

Pencil beam scanning proton PMRT vs IMRT photon PMRT. All TE/I pts had the tissue expander in place and irradiated, so this cohort speaks to expander-in-situ RT, not to post-exchange irradiation of a permanent implant. Dose and fractionation are not reported in source.

Proton was associated with CC on univariate analysis (HR 2.3, 1.26-4.30, P=.007) but the association did not hold after adjustment (HR 1.76, 0.93-3.32, P=.083). DTI vs TE/I carried HR 3.0 (1.7-5.5), P < .001 in the multivariable model. No other factor was significantly associated with CC.

Modality was assigned by practice pattern, not randomized, so the residual proton association could be confounding the model did not capture. CC is clinician-graded on unblinded chart review, and the DTI cells are thin (36 proton, 15 photon), which is where the widest rate gap sits.

The paper set out to test a prespecified suspicion that protons increase CC and returned a trend that did not clear significance once reconstruction type entered the model. What it does establish is the interaction cell worth counseling on: proton + DTI at 50% CC at 2 years.

Retrospective, non-randomized modality assignment with baseline imbalance in reconstruction type and laterality; the proton signal loses significance once adjusted.