ASTRO Annual Meeting 2024
SUPREMO
ForPost-mastectomy breast, node-negative high-risk or 1-3 positive nodes
TL;DREditorial critique: chest-wall-only RT cut 10yr CW recurrence 1.1% vs 2.5% (HR 0.45) but RNI was prohibited.
The RT-relevant number is buried in SUPREMO's supplement: node-positive LRR 3.3% vs 4.8%, HR 0.51 (0.27-0.96), significant even with chest-wall-only fields and RNI prohibited. With supraclavicular coverage in 12% and IMN in under 2%, this trial never tested comprehensive PMRT, so it cannot settle the elective nodal decision.
In a post-mastectomy patient with 1-3 positive nodes staged by SLNB alone, this argues SUPREMO does not license PMRT omission; it says nothing about node-negative pts without adverse features, where EBCTCG also found no benefit.
The supplement carries the number the headline drops: node-positive LRR 3.3% vs 4.8%, HR 0.51 (0.27-0.96), achieved even with RNI prohibited, supraclavicular coverage in 12% and IMN in under 2%. SUPREMO therefore constrains chest-wall-only treatment, not the elective nodal volume decision.
Axillary staging gates how far SUPREMO travels: only 14% had SLNB alone, and roughly 30% of SLNB pts with 1-3 positive nodes harbour further nodes at completion ALND. Choosing ALND to justify skipping PMRT trades a 8% five-year lymphedema risk with SLNB alone for 25% with ALND alone.
Also covered Jul 7
9 details
ASO Perspectives editorial in Annals of Surgical Oncology, not new trial data. Two radiation oncologists re-read SUPREMO against the PMRT and RNI evidence base. PMRT after neoadjuvant therapy is explicitly out of scope.
The central claim is that SUPREMO tested chest wall alone, not PMRT: RNI was prohibited, supraclavicular nodes were covered in 12% of PMRT-arm pts (n=97), and internal mammary irradiation occurred in fewer than 2% across both arms. Non-UK centres could give RNI in the observation arm, and 12 control pts received supraclavicular RNI.
Only 25% were truly node-negative and would not be offered PMRT under current guidelines; the majority had N1 disease (1-3 nodes). 65% were hormone-receptor positive, TNBC was 10%, and only 14% had SLNB alone with the majority undergoing ALND.
SUPREMO's 10-year chest-wall recurrence fell from 2.5% to 1.1% (HR 0.45) with no gain in overall LRR, DFS or OS. The supplement carries the signal the headline drops: LRR 4.8% to 3.3%, HR 0.51 (95% CI 0.27-0.96) in node-positive pts, not in node-negative.
| Approach | 5yr lymphedema risk |
|---|---|
| SLNB alone | 8% |
| SLNB + RNI | 11% |
| ALND alone | 25% |
| ALND + RNI | 30% |
EBCTCG 2014 found PMRT cut 10-year LRR by 17.9% and 20-year breast cancer mortality by 8% in 1-3 node-positive women, persisting with a single positive node, with no node-negative benefit. MA-20 and EORTC 22922 both showed RNI benefit in 1-3 node-positive disease despite near-universal ALND, and a later EBCTCG RNI meta-analysis showed gains at 15 years including in contemporary systemic-therapy trials.
This is a single-perspective editorial from two radiation oncologists, so the framing selects evidence favouring comprehensive RNI, and the reader gets no independent re-analysis of SUPREMO's data. Its strongest number, the node-positive LRR HR 0.51, comes from a supplementary subgroup the trial did not power for.
The authors leave the genuinely open questions to trials in progress: MA.39 (Tailor-RT) for RNI omission at low recurrence score, T-Rex for RNI omission in hormone-sensitive disease with one to two macrometastatic SLNs. They also note the surgical corollary, that ALND should not be chosen to earn a PMRT omission, since ALND is the dominant lymphedema driver.
Editorial, no new data; contests the omission reading of SUPREMO on field design and population grounds, aligning with ASTRO 2025 and NCCN rather than the trial's public messaging.
- RNI omission in 1-3 node-positive pts staged by SLNB alone
- Whether low Oncotype score permits comprehensive RNI omission
- PMRT effect in triple-negative disease after mastectomy
📚 Sources · 📄 1 paper
ASTRO 2024: SBRT for Unfavorable Intermediate-Risk Prostate Cancer
TL;DRConference education session on SBRT for UIR prostate: 5 fractions over 1-2wks, 1-2% bothersome toxicity vs 10-30% with 45-fraction 2D era.
Reported via UroToday →
RTOG 9408PACE BHYPO-RT-PCFLAME 2.0FORT
The actionable detail is the urethral-constraint critique of PACE-B: contouring was optional and constrained only "if visualized" (V44Gy <20%), so hotspots ≥120% put ~48Gy (≈121Gy EQD2) on the urethra. That reframes the 5.4% vs 3.7% G2+ GU gap as a planning artifact, not an SBRT property, and argues for contouring and constraining the urethra in 5-fraction prostate plans.
Contour and constrain the urethra in 5-fraction prostate plans: PACE-B made it optional ("if visualized", V44Gy <20%), and plausible ≥120% hotspots mean ~48Gy (≈121Gy EQD2) there, which reframes the 5.4% vs 3.7% G2+ GU gap as planning, not modality. Separately, RTOG 9408 keeps 4mo ADT tied to UIR, not FIR.
14 details 4 trials watching
ASTRO 2024 education session (EDU 16), not a trial report. Dr Daniel Spratt reviews risk stratification, fractionation history, and the SBRT evidence base for unfavorable intermediate-risk prostate cancer.
Unfavorable intermediate-risk disease, defined since 2013 by Gleason grade group 3 (HR 3.49 for distant mets) or ≥2 intermediate risk factors (HR 2.40). FIR and UIR also separate on cumulative PCSM incidence (p=0.013).
Options span brachytherapy and EBRT (protons or photons/IGRT) across conventional (~40fx), moderate hypofractionation (~20fx), and ultra-hypofractionation (~5fx). Era contrast: 1980s 2D delivered 45 fractions over 9 weeks with 10-30% bothersome GU/GI toxicity; modern SBRT is 5 fractions over 1-2 weeks with 1-2%.
RTOG 9408 secondary analysis anchors the ADT question: in UIR, 4mo ADT improved distant metastasis (HR 0.48, 0.28-0.83, P=.008) and PCSM (HR 0.40, 0.26-0.60, P<.001), with no benefit in FIR. PACE-B 5yr showed no significant EFS difference for SBRT vs conventional/moderate hypofractionation.
| Question | Endpoint | Result |
|---|---|---|
| UIR vs FIR prognosis | Distant metastasis | HR 2.36 (95% CI 1.44-3.89), P=.001 |
| UIR vs FIR prognosis | PCSM | HR 1.84 (95% CI 1.29-2.62), P=.001 |
| ADT benefit in UIR | Distant metastasis | HR 0.48 (95% CI 0.28-0.83), P=.008 |
| ADT benefit in UIR | PCSM | HR 0.40 (95% CI 0.26-0.60), P<.001 |
| ADT benefit in FIR | DM / PCSM | No improvement |
PACE-B G2+ GU 5.4% SBRT vs 3.7% control (p=0.28), no significant bowel difference. Pooled SBRT series: late grade ≥3 GU 2.0% (1.4-2.8%) and GI 1.1% (0.6-2.0%), with dose associated with both better biochemical control (P=.018) and worse late G3+ GU (P=.014).
The session's argument is that SBRT toxicity is a planning problem, not a modality problem: PACE-B did not require urethral contouring, so likely hotspots of ≥120% (≥48Gy, ~121Gy EQD2 to urethra) can explain the GU excess. Focal-boost work (36.25Gy/5fx + DIL to 45-50Gy; Loblaw's 35Gy prostate / 25Gy pelvis / 50Gy DIL) points the field toward whole-gland de-escalation with a boost.
Single-speaker synthesis with the speaker's own interpretive framing rather than a systematic review; the urethral-hotspot explanation for PACE-B GU toxicity is inference, not a reported dosimetric analysis. The captured excerpt truncates mid-FLAME 2.0 and never reaches the FORT trial named in the keywords.
- Does mandatory urethral constraint erase SBRT's GU excess? recruiting Daily Adaptive Radiation Therapy Using an Individualized Approach for Prostate Cancer Phase NAn=132 · primary completion 2026-07 · urethral-sparing adaptive SBRT, EPIC-26 acute GU 1° EPn=42 · primary completion 2028-01 · SUPR-SABR urethra sparing vs historical GU tox rates
- Does whole-gland de-escalation with DIL boost preserve biochemical control? n=58 · primary completion 2028-01 · microboost SBRT with whole gland dropped to 30-35 Gy
- Optimal DIL boost dose in 5 fractions n=132 · primary completion 2025-02 · 5-fraction MR-guided SBRT with SIB to the DIL
📚 Sources · 📄 1 paper
Abstract
HYDRA
ForLocalised prostate cancer, definitive external-beam RT
TL;DRNo PFS difference for either isodose (HR 0.92) or dose-escalated MHFRT (HR 0.94), but escalation raises late G2+ GI (OR 1.48).
The split that matters is isodose vs dose-escalated MHFRT, not hypofractionation itself: escalation adds no PFS (HR 0.94, 0.82-1.09) and costs bowel on both physician grading (OR 1.48) and patient report (OR 1.68). GU was unchanged in both strata. The schedule decision lands on 60 Gy in 20 fractions.
In a man with localised prostate cancer starting definitive prostate-only EBRT, this supports an isodose moderately hypofractionated schedule over a dose-escalated one; it does not extend to five-fraction ultrahypofractionation, post-prostatectomy salvage, or whole-pelvis treatment.
The decision this moves is schedule selection, not modality: escalated MHFRT shows no PFS gain (HR 0.94, 0.82-1.09) and raises late G2+ GI (OR 1.48) plus patient-reported bowel decrement (OR 1.68), while isodose shows neither. 60 Gy in 20 fractions is the defensible default for prostate-only volumes.
7 details 5 trials watching
IPD meta-analysis of randomised phase 3 CFRT vs MHFRT trials via the MARCAP consortium. Searches on Dec 15, 2023 and re-run Jan 8, 2025 screened 1696 records down to 7 eligible trials. Three separate analyses: efficacy, physician-scored late toxicity, and patient-reported outcomes.
Localised prostate cancer on trials that published patient-level efficacy AND late toxicity data. 3454 pts across three isodose trials, 2426 pts across four dose-escalated trials. Trials whose CFRT arm fell below modern dose were excluded.
The intervention split is the whole point: isodose MHFRT (same equivalent dose in fewer fractions, eg 60 Gy in 20 fractions) versus dose-escalated MHFRT. The CFRT comparator had to deliver ≥70 Gy in 2 Gy equivalents.
Primary (efficacy): progression-free survival. Co-primary toxicity endpoints: late grade 2 or higher GU and GI. Co-primary PRO endpoints: clinically-significant decrement in urinary or bowel quality of life.
The GI signal sits entirely in the dose-escalated stratum and shows up on both physician grading and patient report; the isodose stratum carries neither. GU odds ran above 1 in both comparisons with intervals crossing unity.
CHHiP and PROFIT established 60 Gy in 20 fractions as non-inferior to conventional fractionation. The escalated schedules were built on the premise that a higher equivalent dose in fewer fractions would improve control; pooled here that premise fails on PFS while adding bowel toxicity.
Toxicity scales and PRO instruments were not uniform across the seven trials, and the dose-escalated stratum pools four schedules that are not interchangeable, so the OR describes escalation as a class, not one regimen. Follow-up also differs between strata (5.4 vs 7.1 yrs).
With efficacy answered as a null, the schedule decision turns entirely on toxicity, and the toxicity difference runs one way. Escalating per-fraction dose beyond isodose buys no measurable PFS while adding bowel morbidity that pts themselves report, which leaves little argument for an escalated MHFRT schedule in intact localised disease.
Pooled IPD from seven randomised phase 3 trials, aligned with existing moderate-hypofractionation practice; refines which regimen rather than establishing a new modality or population.
- Does the escalation bowel signal extend to five-fraction ultrahypofractionation? recruiting Comparing Moderately Ultra Hypofractionated Radiation Treatments for Prostate Cancer Phase 2n=204 · primary completion 2030-11 · randomised 20fx vs 5fx post-op bed +/- pelvisrecruiting Salvage Moderate Hypofractionated Versus Ultrahypofractionated Radiotherapy for Biochemical Recurrence After Radical Prostatectomy in Prostate Cancer Phase 3n=270 · primary completion 2034-12 · phase 3 moderate vs ultrahypo salvage, toxicity EP
- Do rectal spacers and daily IGRT narrow the dose-escalated GI gap? n=500 · primary completion 2027-12 · SpaceOAR Vue for late GI toxicity under SBRTn=84 · primary completion 2027-12 · Barrigel anterior rectal sparing in post-op RT
- Same toxicity read when MHFRT covers whole-pelvis nodal volumes? n=18 · primary completion 2026-08 · 20/16/12fx pelvic nodal RT with prostate SIB