Stereotactic body radiotherapy (SBRT) showed no detected difference in freedom from local progression compared with microwave ablation (MWA) in selected patients with oligometastatic colorectal liver metastases in the prospective, randomized phase 2 LAVA-CRLM trial. SBRT was associated with a more favorable treatment-related safety profile, with fewer patients experiencing grade 2 or higher treatment-related toxicity and no grade 3 or higher treatment-related toxicity reported in the SBRT group.
The results were published in The Lancet Regional Health – Europe in the original article, “Microwave ablation versus stereotactic body radiotherapy for oligometastatic colorectal liver metastases (LAVA-CRLM): a prospective, randomised, phase II trial.”
Authors: Signe Lenora Risumlund, Line Bjerregaard Stick, Ane Appelt, Ivan Richter Vogelius, Bo Nyhuus, Nicolai Aagaard Schultz, Luit Penning, Mette van Overeem Felter, Mirjana Josipovic, and Peter Nørgaard Larsen.
Why LAVA-CRLM Was Conducted
Local treatment plays an important role in carefully selected patients with oligometastatic colorectal liver metastases. Surgical resection remains the standard of care, while local ablative strategies, including thermal ablation and SBRT, are used when appropriate based on disease extent, lesion location, technical feasibility, and multidisciplinary team assessment.
MWA is widely used for thermal ablation and can provide durable local control. However, it is an invasive procedure that typically requires general anesthesia and may require percutaneous, laparoscopic, or open surgical access. SBRT offers a non-invasive alternative and may be particularly relevant for lesions that are technically challenging to ablate or are located near structures where ablation-related complications are a concern.
Before LAVA-CRLM, the authors identified no prospective randomized studies directly comparing MWA and SBRT for liver metastases in patients with oligometastatic colorectal cancer. The trial was designed to provide initial randomized comparative evidence on local control and safety between these two treatment approaches.
Study Design
LAVA-CRLM was an investigator-initiated, prospective, randomized phase 2 trial conducted at two centers in Copenhagen, Denmark: Copenhagen University Hospital, Rigshospitalet, and Herlev Hospital.
Eligible patients were adults with one to three colorectal liver metastases, each measuring 4.0 cm or less. Patients were required to have Child–Pugh class A liver function. Patients with limited extrahepatic disease or an untreated primary tumor could be included if a curative treatment strategy was considered feasible.
All patients were assessed by a hepatopancreatobiliary multidisciplinary team and were included only if they were considered suitable for both MWA and SBRT with curative intent. Eligibility was confirmed with liver ultrasonography and contrast-enhanced MRI. Patients were randomly assigned in a 1:1 ratio to MWA or SBRT. Because of the nature of the treatments, patients and treating clinicians were not blinded. Assessment of the primary endpoint was masked to treatment allocation.
The primary endpoint was freedom from local progression in the modified intention-to-treat population. Local progression was assessed at the patient level and defined as progression of a treated lesion from the time of randomization. Development of new lesions or progression in untreated intrahepatic or extrahepatic lesions was not counted as an event for the primary endpoint.
Secondary endpoints included overall survival, treatment-related grade 3 or higher toxicity, other toxicity outcomes, and health-related quality of life.
Treatment Approaches
MWA was performed by experienced operators under general anesthesia. Treatment could be delivered percutaneously or during open or laparoscopic surgery. Ablation was performed under real-time ultrasound guidance, with energy delivery tailored to tumor size.
SBRT was delivered using either an integrated MRI-linear accelerator or a conventional linear accelerator with cone-beam CT guidance and fiducial tracking. The preferred regimen was 45 Gy in three fractions over one week. When adequate target dosing could not be achieved in three fractions while meeting organ-at-risk constraints, 50 Gy in five fractions over two weeks was used. All SBRT regimens delivered a biologically effective dose greater than 173 Gy to the gross tumor volume.
Follow-up was planned for five years and included clinical evaluation and contrast-enhanced CT of the chest, abdomen, and pelvis every three months for the first two years, every six months during year three, and annually thereafter. MRI was used when CT findings were equivocal or when additional assessment of suspected local progression was clinically needed.
Patient Population
Between January 29, 2019, and December 3, 2024, 100 patients were randomly assigned to SBRT or MWA. Eight patients were excluded from the modified intention-to-treat population because of another primary malignancy, disease progression, or surgical treatment outside the study protocol.
The modified intention-to-treat population included 92 patients who received protocol-defined local therapy: 45 in the SBRT group and 47 in the MWA group. Most patients had a single liver metastasis. Overall, 72 patients had one metastasis, 16 had two, and four had three. The median metastasis size was 1.2 cm.
Synchronous metastases were present in 16 patients in the MWA group and 15 patients in the SBRT group; the remaining patients had metachronous metastases. Chemotherapy within the preceding three months had been received by 16 patients in the MWA group and nine patients in the SBRT group.
KRAS-mutated tumors were reported in 21 patients in the MWA group and 11 patients in the SBRT group, while KRAS status was unknown in nine and eight patients, respectively.
Five patients randomized to SBRT ultimately received MWA because of patient preference, inability to perform breath-hold, or technical limitations, including unmet organ-at-risk dose constraints. The safety population therefore included 40 patients treated with SBRT and 52 treated with MWA.
Local Control Outcomes
At a median follow-up of approximately 35 months, local progression occurred in 15 patients in the SBRT group and 17 patients in the MWA group in the modified intention-to-treat population. The estimated 1-year freedom from local progression was 83.0% with SBRT and 77.7% with MWA. There was no evidence of a difference between treatment groups, with a hazard ratio of 0.87, 95% CI 0.43–1.74, and log-rank p = 0.70.
A post-hoc sensitivity analysis treating death as a competing risk showed a subdistribution hazard ratio of 0.86. After adjustment for baseline prognostic factors, including largest lesion size, KRAS status, number of liver lesions, and distant metastases at baseline, the effect estimate remained similar.
In the per-protocol population, local progression occurred in 12 patients in the SBRT group and 17 patients in the MWA group. The estimated 1-year freedom from local progression was 86.0% with SBRT and 77.7% with MWA, again with no evidence of a difference between groups.
The authors emphasized that the trial was not designed to establish equivalence or non-inferiority between MWA and SBRT. Therefore, the absence of a statistically significant difference should not be interpreted as proof that the two treatments are equivalent.
Overall Survival
After a median follow-up of 46.8 months in the SBRT group and 45.5 months in the MWA group, 19 patients in the SBRT group and 20 patients in the MWA group had died in the modified intention-to-treat population. Estimated 1-year overall survival was 88.9% with SBRT and 95.7% with MWA. Estimated 3-year overall survival was 71.5% and 63.3%, respectively. There was no evidence of a difference between groups, with a hazard ratio of 0.91 and log-rank p = 0.80.
In the per-protocol population, 15 patients in the SBRT group and 20 patients in the MWA group had died, with no evidence of a difference between treatment groups.
Safety Findings
The safety findings favored SBRT for treatment-related toxicity. During treatment or within one month after treatment, any-grade toxicity occurred in 15 patients treated with SBRT and 37 patients treated with MWA. Grade 2 or higher treatment-related toxicity occurred in one patient in the SBRT group and 13 patients in the MWA group.
Grade 3 or higher treatment-related toxicity occurred only in the MWA group, affecting four patients. This included one treatment-related death. The patient was admitted with abdominal pain two days after percutaneous MWA; exploratory laparotomy revealed hepatic necrosis with capsular perforation, and the patient died the same day.
During follow-up, any-grade toxicity occurred in 23 patients in the SBRT group and 30 patients in the MWA group. Grade 3 adverse events during follow-up were observed in one patient in the SBRT group and three patients in the MWA group, but none were considered treatment related.
The 1-year cumulative incidence of grade 2 or higher toxicity during follow-up was 7.5% with SBRT and 20.7% with MWA. At three years, the cumulative incidence was 24.6% and 32.7%, respectively. There was no evidence of a difference between groups in this analysis.
Quality of Life
Health-related quality-of-life data were available for 89 patients, representing 98% of the study population. A total of 441 EORTC QLQ-C30 questionnaires were completed. There was no evidence of a difference between SBRT and MWA in the EORTC QLQ-C30 summary score during follow-up. No evidence of a difference was observed in individual functional or symptom scales.
The authors noted that long-term quality-of-life outcomes may be influenced by disease progression and systemic therapy, which could limit the ability to detect differences between local treatment modalities.
Interpretation and Limitations
LAVA-CRLM provides prospective randomized evidence comparing MWA and SBRT in patients with oligometastatic colorectal liver metastases selected for curative-intent local therapy and considered technically suitable for both approaches. The study found high local control with both modalities and no detected difference in freedom from local progression. However, SBRT showed a more favorable treatment-related safety profile, with fewer patients experiencing grade 2 or higher treatment-related toxicity and no grade 3 or higher treatment-related toxicity.
Several limitations are important. This was a phase 2 trial with a relatively small sample size and was not powered to establish equivalence or non-inferiority. The confidence intervals were wide and remain compatible with clinically relevant differences between treatments.
The study was conducted within a single institutional network in Denmark, which may limit generalizability to other settings with different patient populations, workflows, referral patterns, and technical expertise. Molecular profiling was not systematically available at enrollment, and KRAS-mutated tumors were numerically more frequent in the MWA group, which may have influenced local control estimates.
Although patients with lesions up to 4.0 cm were eligible, all treated metastases were 3.0 cm or smaller. As a result, evidence for intermediate-sized lesions remains limited.
Takeaway
In the randomized phase 2 LAVA-CRLM trial, SBRT and MWA showed no detected difference in freedom from local progression among selected patients with oligometastatic colorectal liver metastases measuring 3 cm or smaller. SBRT demonstrated a more favorable treatment-related safety profile, with no grade 3 or higher treatment-related toxicity reported.
The findings support consideration of SBRT as a non-invasive local treatment option alongside MWA in multidisciplinary treatment planning, while emphasizing the need for individualized decision-making based on patient characteristics, lesion location, technical feasibility, and institutional expertise.
The full article is available in The Lancet Regional Health – Europe.
