COLLISION XL: Unresectable Colorectal Liver Metastases (3-5cm): Stereotactic Body Radiotherapy vs. Microwave Ablation

COLLISION XL: Unresectable Colorectal Liver Metastases: Stereotactic Body Radiotherapy vs. Microwave Ablation - a Phase II Prospective Randomized Controlled Trial for Intermediate-size (3 - 5 cm) Colorectal Liver Metastases

Multiple articles report that thermal ablation is a safe and effective treatment for unresectable colorectal liver metastases (CRLM) ≤3cm. However efficacy of thermal ablation decreases with increasing lesion size. Guidelines state that thermal ablation is the preferred option for unresectable CRLM ≤3cm and stereotactic body radiotherapy (SBRT) when thermal ablation is not possible. It remains uncertain what local treatment method should be recommended for unresectable CRLM of 3-5cm.

Objective: The primary objective of this study is to compare efficacy of MWA to the efficacy of SBRT with regards to the primary endpoint (local tumour progression free survival at 1 year [1-year LTPFS]) in patients with unresectable CRLM (3 - 5 cm) that are unsuitable for surgery due to either comorbidities, a history of extensive abdominal surgery, a poor performance status or due to a certain unfavourable anatomical location of the tumour.

Study design: COLLISION XL is a prospective multi-centre phase-II randomized controlled trial.

Study population: 68 patients with 1-3 unresectable lesions of 3 - 5cm, unsuitable for (further) chemotherapy regimens, suitable for both MWA and SBRT and no or limited extrahepatic disease (1 extrahepatic lesion is allowed, not including positive para-aortal lymph nodes, celiac lymph nodes, adrenal metastases, pleural carcinomatosis or peritoneal carcinomatosis) are considered eligible. Supplementary resections for resectable lesions and thermal ablations for unresectable CRLM ≤3cm are allowed. A maximum number of 10 CRLM are allowed for patients with no extrahepatic disease and a maximum number of 5 lesions are allowed for patients with limited extrahepatic disease.

Intervention: SBRT or MWA. The panel, consisting of at least two interventional radiologists, two hepatobiliary surgeons and two radiation oncologists, will appoint lesions of 3-5cm that are unresectable and suitable for both MWA and SBRT, as target lesions. All lesions that are not suitable for ablation should be resectable and all unresectable lesions <3cm should be suitable for thermal ablation.

Main study parameters/endpoints: Primary endpoint is local tumour progression free survival (LTPFS) at 1 year from randomization. Secondary endpoints are local tumour progression free survival time, OS, disease-free survival (DFS), time to progression (TTP), procedural morbidity/toxicity and mortality, assessment of pain and quality of life (QoL) and cost-effectiveness ratio (ICER).

Inclusion Criteria:

• 1-3 unresectable CRLM size 3-5 cm eligible for both MWA and SBRT (target lesions);
• Additional CRLM are allowed if considered either resectable or ablatable and <3cm
• No or limited extrahepatic disease (1 extrahepatic lesion is allowed, not including positive para-aortal lymph nodes, celiac lymph nodes, adrenal metastases, pleural carcinomatosis or peritoneal carcinomatosis);
• For subjects with liver only disease the maximum number of CRLM is 10; for subjects with limited extrahepatic disease the maximum number of CRLM is 5;
• Prior focal liver treatment is allowed
• Subjects without prior focal liver treatment should be either unsuitable for 1st line chemotherapy or have progressed under/after 1st-line chemotherapy;
• Subjects with recurrent (either local or distant-hepatic) CRLM after previous focal treatment should be unsuitable for (further) systemic therapy (further downsizing or conversion to resectable disease improbable).

Exclusion Criteria:

• Compromised liver function (e.g. signs of portal hypertension, INR > 1,5 without use of anticoagulants, ascites);
• Pregnant or breast-feeding subjects;
• Immunotherapy ≤ 6 weeks prior to the procedure;
• Chemotherapy ≤ 6 weeks prior to the procedure;
• Severe allergy to contrast media not controlled with premedication.