Oligometastatic / Mets
2026-09-26
LAVA-CRLM NCT03654131
For1-3 oligometastatic CRLM ≤4 cm (treated ≤3 cm), Child-Pugh A, curative intent
HR 0.87
95% CI 0.43-1.74, p=0.70; 1-yr 83.0% vs 77.7%, not met
TL;DR1-yr freedom from local progression 83.0% SBRT vs 77.7% MWA (HR 0.87, p=0.70); treatment-related G2+ toxicity 3% vs 25% in oligometastatic CRLM.
The dose and platform set the transfer bar: 45 Gy/3 fx at the 67% isodose, BED10 >173 Gy to GTV, 88% on MR-linac with daily adaptation, and no G3+ toxicity vs 4 (8%) after MWA. SBRT's case rests on that toxicity gap for small lesions, not on a local control win.
In pts with 1-3 CRLM ≤3 cm judged suitable for both ablation and SBRT, this supports SBRT as a non-invasive alternative when ablation access or procedural risk is the concern; it does not extend to 3-4 cm lesions or to settings without ablative-dose delivery. The longer read
Ablative dosing (45 Gy/3 fx, BED10 >173 Gy to GTV) on MR-linac with daily adaptation produced no G3+ toxicity and a 1-yr FFLP of 83.0%. The transfer question is platform: only 5 pts were treated on a conventional linac, so non-MR centres lack direct support.
For HPB teams, MWA carried 4 (8%) G3+ events including a fatal hepatic necrosis with perforation, vs none with SBRT, at no detectable local control cost for lesions ≤3 cm. Resection remains standard; this informs the non-resection choice, where SBRT can spare anaesthesia and open or laparoscopic access.
10 details
Investigator-initiated randomised phase II, 1:1, two Danish centres, no stratification. N=100 randomised Jan 2019 to Dec 2024; mITT 92. Open-label, with masked 1° endpoint imaging review.
1-3 CRLM, each ≤4.0 cm, Child-Pugh A, liver volume ≥700 mL, no prior liver RT. MDT-deemed suitable for both MWA and SBRT; limited extrahepatic disease allowed if curative strategy feasible. Median lesion 1.2 cm; 78% had a single metastasis.
45 Gy/3 fx preferred, 50 Gy/5 fx when OAR constraints required, prescribed to the 67% isodose; PTV 10 mm craniocaudal, 5 mm radial. BED10 >173 Gy to GTV in all. 88% on MR-linac with daily online adaptation.
Primary: patient-level freedom from local progression of treated lesions (new lesions not events). Secondary: OS, treatment-related G3+ toxicity, late G2+ toxicity; EORTC QLQ-C30.
Acute G2+ 1 (3%) SBRT vs 13 (25%) MWA; G3+ only after MWA, 4 (8%) including one death from hepatic necrosis with capsular perforation. Liver pain G1 in 3 (7.5%) SBRT vs 25 (48%) MWA. QoL did not differ.
Authors cite MWA local control exceeding 90% and 1-yr SBRT LC ranging 50% to 95% in prior, largely retrospective series. Dose here clears Kang's BED10 >117 Gy threshold for ~90% 1-yr LC, so a dose deficit does not explain SBRT's result.
KRAS-mutant disease was 45% vs 24% in the MWA vs SBRT arms, with no molecular stratification; Hong reported KRAS-mutant 1-yr LC 43% vs 72%, a large enough modifier to move arm estimates. Single institutional network; post-protocol systemic therapy uncontrolled.
The trial gives the first randomised head-to-head data, not an equivalence claim; a null HR with CI 0.43-1.74 leaves room for either modality to be meaningfully better. What it settles more firmly is that SBRT avoids the invasive-procedure harms MWA carries.
| Endpoint | SBRT | MWA | Effect |
|---|---|---|---|
| 1-yr FFLP, mITT | 83.0% (72.3-95.4) | 77.7% (66.5-90.9) | HR 0.87 (0.43-1.74), p=0.70 |
| 1-yr FFLP, per-protocol | 86.0% (75.3-98.2) | 77.7% (66.5-90.9) | HR 0.78 (0.37-1.63), p=0.50 |
| 3-yr OS, mITT | 71.5% (58.3-87.7) | 63.3% (49.3-81.2) | HR 0.91 (0.48-1.70), p=0.80 |
| Toxicity | SBRT | MWA | Test |
|---|---|---|---|
| G2+ acute (≤1 mo) | 1 (3%) | 13 (25%) | n/a |
| G3+ acute (≤1 mo) | 0 (0%) | 4 (8%), incl 1 death | Fisher p=0.13 |
| 1-yr cumulative G2+ | 7.5% (1.9-18.4) | 20.7% (10.6-33.1) | Fine-Gray HR 0.51 (0.21-1.24) |
| 3-yr cumulative G2+ | 24.6% (9.8-42.9) | 32.7% (18.5-47.6) | Gray's p=0.13 |
CONSORT flow
Randomised but small phase II powered for HR 0.38, not equivalence; null 1° EP with wide CI cannot establish SBRT matches MWA. Toxicity underpowered.
- Does SBRT match MWA for 3-4 cm colorectal liver metastases?
- Does KRAS/TP53 status modify SBRT vs MWA local control?
- Would a powered non-inferiority trial confirm local control parity?
📚 Sources · 📄 1 paper
2026-05-18 ESTRO Congress 2026
EXTEND
ForOligometastatic solid tumors, 1-5 metastases, on standard systemic therapy
HR 0.54
95% CI 0.41-0.72, p<0.001
TL;DRPFS HR 0.54 (0.41-0.72), p<0.001 for MDT added to SOC across 6 oligometastatic baskets; RT delivered 98% of MDT.
The prostate-excluded HR 0.60 (0.40-0.89) is the number that matters for an RT reader: the benefit survives removal of the two prostate baskets, where MDT is already routine. RT delivered 98% of MDT (370/379), so this is a radiotherapy result, though dose and fractionation are not reported in source.
In a patient with 1-5 metastases from pancreas or a non-breast, non-kidney histology already on standard systemic therapy, this supports discussing MDT as an addition rather than a deferral; it does not resolve the breast or kidney question, where the baskets were inconclusive. The longer read
RT delivered 98% of MDT (370/379 metastases), so the all-basket HR 0.54 and the prostate-excluded HR 0.60 (0.40-0.89) are radiotherapy effect sizes. The prostate-excluded analysis is the one that moves practice beyond the population where MDT is already routine, though dose, fractionation and target volume are not reported in source.
MDT was added on top of standard systemic therapy rather than substituted for it, so nothing here supports deferring or de-escalating systemic treatment. The ctDNA findings (detectable at enrollment with shorter PFS, clearance at 3 months with better survival) are the medonc-relevant signal, pointing toward a molecular rather than lesion-count definition of who to refer.
13 details 5 trials watching
Multicenter randomized phase II basket trial, 6 histology baskets with basket-specific stratification and powering. Accrual 2018 to 2023, median follow-up 53 months.
Patients with 1-5 metastases on standard-of-care systemic therapy, allocated to breast, pancreas, kidney, two prostate baskets, or an "Other" basket. 521 screened, 350 randomized, 334 analyzed per protocol (MDT+SOC n=166; SOC n=168).
Radiotherapy delivered 98% of MDT (370/379 metastases), so this is effectively a radiotherapy trial. Dose, fractionation, technique and target-volume definition are not reported in source.
Primary: PFS, pre-specified in the per-protocol set at three levels (within each basket, across all baskets, and across all baskets excluding the prostate baskets). Exploratory: ctDNA and immune profiling.
All-basket PFS HR 0.54 (95% CI 0.41-0.72), p<0.001; excluding prostate, HR 0.60 (95% CI 0.40-0.89). Superiority in pancreas, prostate and "Other"; breast and kidney inconclusive. No per-basket effect sizes reported in source.
SABR-COMET randomized 99 patients across mixed histologies; STOMP and ORIOLE were prostate-only and smaller. EXTEND's contribution is scale plus histology resolution: it keeps a benefit when the prostate baskets are removed, which the prostate-only trials could not address.
The primary analysis is per-protocol rather than ITT, and an unblinded PFS endpoint in a trial that ablates the very lesions being measured favors the intervention arm. The "Other" basket is a mixed-histology pool, so its superiority signal is the hardest of the three to carry into a single phase III.
The prostate-excluded HR 0.60 is the trial's most load-bearing number, since it shows the pooled result is not simply the prostate literature reasserting itself. The ctDNA correlations (detectable at enrollment with worse PFS and survival; clearance at 3 months with better survival) point at a biological rather than anatomic definition of oligometastasis, which is the more interesting question EXTEND raises without settling.
CONSORT flow
Randomized phase II, per-protocol primary, histology-specific signals explicitly framed as hypothesis-generating for phase III. Consistent with SABR-COMET / STOMP / ORIOLE direction.
- Does MDT-driven PFS benefit translate to overall survival n=340 · primary completion 2026-11 · OLIGAMI: randomised MDT after 12wk systemic, breastactive Stereotactic Ablative Radiotherapy for Comprehensive Treatment of Oligometastatic (1-3 Metastases) Cancer Phase NAn=330 · primary completion 2030-11 · SABR-COMET-style RCT with OS as primary, 1-3 mets
- Can ctDNA select oligometastatic patients for MDT n=60 · primary completion 2027-12 · SABR cohort tracking ctDNA dynamics as biomarker
- Confirmatory phase III in pancreas oligometastatic disease recruiting Stereotactic Body Radiotherapy in Patients With Rare Oligometastatic Cancers (OligoRARE) Phase NAn=200 · primary completion 2028-08 · phase III SBRT+SOC, OS endpoint, pancreas among sitesactive SENECA: First Line metaStatic pancrEatic caNcer Primary and Distant (if Oligometastatic) lEsion direCted rAdiotherapy Phase 3n=108 · primary completion 2030-01 · randomised phase 3 SBRT vs chemo alone, 1L met pancreas
📚 Sources · 📄 1 paper
Abstract
2026-05-17 ESTRO Congress 2026
OligoCare
ForOligometastatic solid tumors treated with SABR, mixed primaries and lesion sites
TL;DRReal-world SABR local failure 5.0% at 1yr, 11.4% at 3yr across 2447 pts / 3533 lesions; CRC worst at 19.6%.
The actionable RT signal is minimum PTV dose, called the single most critical technical factor, and the de novo vs repeat OMD gap the authors attribute to higher delivered dose. CRC failed most (19.6% at 3yr) despite the highest median dose per fraction, which argues for escalation or combination rather than coverage alone. No dose thresholds are reported in source.
For a prostate or NSCLC oligomet being planned for SABR, this real-world cohort supports expecting durable in-field control (8.1% and 9.8% failure at 3yr); it does not support the same expectation for a colorectal met, where 3yr failure reached 19.6%. The longer read
Minimum PTV dose is named the most critical technical factor, so coverage of the low-dose region, not the prescription isodose, is where the planning attention goes. CRC failed worst (19.6% at 3yr) despite the highest median dose per fraction, so escalation alone may not close that gap. No dose thresholds reported in source.
SABR delivers 88.6% in-field control at 3yr in routine practice, so local failure is not the dominant driver of progression in most oligometastatic primaries. The exception is colorectal, at 19.6% failure by 3yr, where the authors suggest combination systemic approaches alongside local therapy rather than dose escalation alone.
| Primary | Total | 1 year | 3 years |
|---|---|---|---|
| Colorectal | 518 | 9.3% | 19.6% |
| Breast | 378 | 4.1% | 11.3% |
| NSCLC | 530 | 6.0% | 9.8% |
| Prostate | 1021 | 2.7% | 8.1% |
+2 more figures
10 details 4 trials watching
Prospective EORTC OligoCare registry cohort, interim analysis. 57 institutions, enrolment July 2019 to July 2025. No randomisation and no comparator arm; technique and dose were chosen by the treating institution.
2447 eligible pts with 3533 lesions. Median age 69 (range 28-94), 69% male. Primaries reported for the local-control breakdown were prostate (1021), NSCLC (530), colorectal (518) and breast (378).
SABR to oligometastatic lesions across bone (869 non-vertebral, 515 spine), lung (807), non-regional nodes (558), liver (306), brain (231) and other (247) sites. Minimum PTV dose was the technical factor most associated with outcome; specific dose and fractionation schedules are not reported in source.
Local in-field progression, reported as cumulative incidence with 99% CI, at 1 and 3 years. Median follow-up 31 months, minimum 6 months.
Overall local in-field progression 5.0% at 1yr and 11.4% at 3yr, ie 88.6% local control at 3yr. By primary, colorectal was the outlier and prostate the best.
Randomised oligometastatic SABR trials (SABR-COMET, STOMP, ORIOLE) were built on much smaller, more selected cohorts and reported survival or progression endpoints rather than lesion-level in-field control at this scale. This registry does not test the SABR question those trials asked; it reports what in-field control looks like once SABR is delivered in routine multi-institutional practice.
Dose and fractionation were institution-chosen, so the minimum-PTV-dose association is confounded by target site, prior irradiation and case selection. No PTV dose threshold, no per-primary dose data and no toxicity are reported in source, so the technical conclusion cannot be translated into a planning constraint.
The CRC finding is the one that changes a plan: worst local control despite the highest median dose per fraction points at intrinsic radioresistance rather than underdosing, and the authors call for escalation or combination strategies. The de novo versus repeat OMD gap is reported as a dose effect, which is plausible but is exactly the kind of comparison a registry cannot separate from the reasons a lesion is being re-treated.
Prospective multi-site registry, no randomised comparator, institution-chosen technique. Large real-world cohort supports existing SABR practice in OMD rather than testing it.
- Minimum PTV dose threshold that predicts local control
- Combination or dose-escalation strategies for colorectal oligomets recruiting Fruquintinib Combined With Sintilimab ± Radiotherapy for Third-line Treatment of Colorectal Cancer With Liver Metastases Phase 2n=62 · primary completion 2026-10 · SBRT+LDRT with sintilimab/fruquintinib, MSS CRC liverrecruiting Low and Intermediate Risk OliGometastatic ColoREctal CancEr PatieNts Treated with Stereotactic ABlative Radiotherapy Phase NAn=204 · primary completion 2031-04 · randomised SABR + chemo in 1-3 CRC oligomets
- Whether repeat OMD failure reflects dose or disease biology active Bony M - Stereotactic Ablative Radiotherapy (SABR) of Bony Metastases in Patients With Oligometastatic Disease Phase NAn=67 · primary completion 2023-01 · SABR in de novo vs recurrent OMD bone lesionsn=397 · primary completion 2028-06 · MR-guided adaptive SBRT, tumor control by site
📚 Sources · 🐦 1 tweet
📣 #ESTRO26 - @UmbertoRicardo e2irradiate @EORTC prospective OLIGOCARE registry of SABR for oligomets. ~2500 patients, ~3500 mets.
— Shankar Siva (@_ShankarSiva) May 17, 2026
➡️ local failure 5% at 1 year and 11% at 3 years
➡️ Colorectal cancer has higher risk of progression
➡️ minimum PTV dose correlated with outcome… pic.twitter.com/cx4zERqHhK