collision xl: unresectable colorectal liver metastases (3-5cm): stereotactic body radiotherapy vs. microwave ablation

Conditions: Colorectal Cancer Metastatic; Liver Metastasis Colon Cancer

Summary: 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).

Eligibility criteria:
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.