ASCO Genitourinary Cancers Symposium 2022
Organs at Risk Radiation Dose Constraints: 2025 Update
TL;DRSFRO 2025 OAR dose-constraint update: normofractionated, moderate hypofractionated and ablative tables across skull base, H&N, lung, breast, oesophagus, liver.
START BFAST-FORWARDRTCMIENDOMETRE
The practical shift is coverage of ablative regimens per fraction number (1, 3, 4, 5, 8) alongside normofractionation, plus cardiac substructures (LAD, left ventricle) and a proposed dorsal vagal complex OAR. Numbers are tiered optimal vs mandatory, so a plan that exceeds an optimal value is a documented conversation, not a violation.
Practical shift is the per-fraction-number ablative columns (1, 3, 4, 5, 8) sitting alongside normofractionation in one grid, plus cardiac substructures (LAD, left ventricle) as constrained organs. The optimal versus mandatory tiering is what changes planning behaviour: it names which values are negotiable against target coverage.
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SFRO consensus update, part of the RecoRad 4th edition, covering adult external beam radiotherapy and brachytherapy practice. Constraints were compiled from international consensus guidelines and clinical trial data, then validated by national reference experts rather than derived from a new dataset.
Tables are indexed by tumour site and by fractionation: normofractionation, moderate hypofractionation, accelerated hyperfractionation (lung), and ablative regimens split by fraction number (1, 3, 4, 5, 8). Dmax is approximated by D2 % in normofractionation and D0.035 cm3 in stereotactic plans; several hypofractionated entries are given as EQD2.
No clinical endpoint. The deliverable is a set of dose-volume objectives intended for direct implementation into treatment planning systems as standardized clinical objectives.
Constraints are tiered as optimal versus mandatory, with ALARA used where no numeric threshold is offered (parotid in the brain table, lacrymal gland under moderate hypofractionation). The authors require that pts be informed of the risk when a constraint is exceeded.
Breast constraints are anchored to the schedules of START B (40 Gy in 15) and FAST-FORWARD (26 Gy in 5); liver constraints are built on the ASTRO clinical practice guideline across 3, 5 and ≥ 20 fractions. This is a national harmonization layer over those sources, not a competing evidence synthesis.
The authors state most constraints still rest on 3D conformal-era data, which sits awkwardly with IMRT's larger low-dose bath and with ablative dose gradients. Biological modifiers of risk (individual radiosensitivity, genomic profile, concurrent immunotherapy) are not accounted for, and dose to immune organs at risk is named as unresolved.
The value here is harmonization, not novelty: the stated problem is the multiplicity of circulating constraint sets and the absence of a single reference. The optimal/mandatory tiering is the part that changes daily behaviour, because it tells a planner which values are negotiable against target coverage and which are not.
- Validity of 3D conformal-derived constraints under IMRT and SBRT
- Dose thresholds for immune organs at risk with concurrent immunotherapy
- Dorsal vagal complex as an OAR for radiation-induced nausea
📚 Sources · 📄 1 paper
HERO
ForAdvanced prostate cancer, completing 48wk ADT, no ongoing ADT planned
TL;DR90-day testosterone recovery to ≥280 ng/dL 53.9% with relugolix vs 3.2% with leuprolide after 48wk ADT.
Reported via UroToday →
For intermediate-risk prostate cancer treated with RT plus short-course ADT, the recovery kinetic is the deliverable: median 86.0 days to normal T on relugolix vs 2 of 47 recovering on leuprolide by day 90. That gates the choice of agent when ADT is a fixed 4 to 6 month adjunct to RT and the goal is off-treatment hypogonadism time, not depth of suppression.
In men finishing a defined short-course ADT with RT and no plan for ongoing suppression, this informs agent choice on recovery speed; it does not apply to men continuing ADT indefinitely or to those where prolonged suppression is the therapeutic aim.
When ADT is a defined 4 to 6 month adjunct to definitive RT, agent choice can be made on recovery speed rather than suppression depth. Median 86.0 days to normal testosterone (95% CI 65.0, 92.0) on relugolix is a concrete planning figure for counselling on off-treatment hypogonadism.
Relevant only where ADT is time-limited by design. The parent trial's depth advantage (96.7% vs 88.8% sustained castration) and this recovery signal point the same way, but neither is tied to an oncologic endpoint, so sequencing and continuous-suppression decisions are untouched.
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Subset analysis of the phase 3 HERO trial, which randomized 934 men with advanced prostate cancer 2:1 to relugolix or leuprolide for 48 weeks. This report covers a 90-day recovery period after treatment discontinuation.
184 men who completed 48 weeks of assigned therapy and had no plan to start alternative ADT within the next 12 weeks (24 weeks after a last leuprolide 3-month depot). 137 had received relugolix, 47 leuprolide.
Relugolix 120 mg orally once daily after a single 360 mg loading dose on Day 1, versus leuprolide injections every 12 weeks, each for 48 weeks.
Time to testosterone recovery to ≥280 ng/dL by Kaplan-Meier, PSA during the recovery phase, and adverse events during recovery. No oncologic efficacy endpoint in this analysis.
During recovery, 96% of men had at least one adverse event and 15% had a grade ≥3 event, similar in both groups.
The 90-day window sits inside the pharmacologic tail of a 3-month leuprolide depot, so part of the 53.9% vs 3.2% gap is measurement timing rather than a durable biologic difference. The leuprolide median of 112.0 days derives from 2 recovery events.
Consistent in direction with the parent HERO result, where relugolix gave deeper sustained castration (96.7% vs 88.8%, difference 7.9%, 95% CI 4.1 to 11.8, P<0.001). The trade the two readings define is depth of suppression on-treatment against speed of recovery off-treatment, both favoring the oral antagonist.
This settles a kinetic question, not a clinical one: no recurrence, quality-of-life, or cardiometabolic endpoint is tied to the faster recovery here. Whether restoring normal testosterone months earlier translates into measurable benefit, or into a PSA that reflects recovering physiology rather than disease, remains untested.
| Metric | Relugolix | Leuprolide |
|---|---|---|
| n in recovery subset | 137 | 47 |
| Baseline T entering recovery (mean±SD) | 427±142 ng/dL | 404±127 ng/dL |
| Recovered T | 74 | 2 |
| Median time to recovery | 86.0 d (95% CI 65.0, 92.0) | 112.0 d (95% CI 112.0, NE) |
| Median PSA at day 90 | 0.39 ng/mL (0 to 233.1) | 0.06 ng/mL (0 to 14.0) |
Post-hoc subset of a phase 3 trial, non-randomised entry criterion, 137 vs 47 arms; recovery kinetics are a pharmacologic expectation, not a new clinical outcome.
- Does faster testosterone recovery change QoL or cardiometabolic outcomes
- Is higher day-90 PSA on relugolix physiologic or disease-driven
- Recovery kinetics after short-course ADT with definitive radiotherapy