Oligometastatic / Mets
SBRT vs thermal ablation for small CRLM: first randomised LC data, but the trial was not built to show equivalence.
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.
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.
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