Ablation vs Resection of Colorectal Cancer Liver Metastases

Study Overview
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Brief Summary
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230 patients with colorectal cancer liver metastases will be randomly assigned to resection or thermal ablation.

Detailed Description
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Rationale: The use of thermal ablation of liver tumors is rapidly increasing. This is despite a lack of high-level evidence of the oncologic efficacy of ablation. Ablation is most often used in cases where resection is not possible, but as the technique has improved it is increasingly used as a substitute for resection. A majority of studies on ablation are hampered by selection bias. Selection bias can only be overcome in a randomized controlled trial. Primary objective: To compare rates of local tumor progression within 12 months in patients randomly assigned to thermal ablation or surgical resection of colorectal liver metastases. Secondary objectives: To establish a pipeline for immediate three-dimensional verification of the ablated zone following thermal ablation of liver metastases. To compare health related quality of life in patients randomly assigned to thermal ablation or surgical resection of colorectal liver metastases. To perform a cost-effectiveness analysis (Cost per quality adjusted life year) of thermal ablation and resection of colorectal liver metastases. To compare disease-free and overall survival in in patients randomly assigned to thermal ablation or surgical resection of colorectal liver metastases. To evaluate the hemodynamic response to thermal ablation and laparoscopic resection of liver tumors. Study design: A randomized, controlled, multicenter, double-blinded non-inferiority trial. Study population: Two groups of 115 patients (230 in total) with colorectal liver metastasis eligible for radical treatment using EITHER resection OR ablation (not a combination). Intervention: Ablation of colorectal liver metastases Control: Resection of colorectal liver metastases Main study parameters/endpoints: The primary endpoint of the study is local recurrence of cancer at 12 months. Secondary endpoints include overall survival, disease free survival, health related quality of life, postoperative pain, complications, hospital stay and cost-effectiveness.

Official Title
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A Randomized Controlled Trial of Needle Ablation With 3D Verification vs Surgical Resection of Colorectal Cancer Liver Metastases

Conditions
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Colorectal Cancer Metastatic

Intervention / Treatment
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* Procedure: Surgical resection
* Procedure: Thermal ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically verified colorectal cancer Colorectal liver metastases (proven or suspected) eligible for radical treatment using EITHER resection OR ablation (not a combination), as decided by the liver MDT meeting at the study center The patient is fit to undergo both resection and ablation of all liver metastases Size of largest lesion up to and including 30 mm In case of solitary metastasis, resection plan includes resection of ≤ 2 anatomical segments. In case of multiple metastases in one continuous resection, resection plan can include ≤ 4 anatomical segments (including hemihepatectomy) ≤ 5 tumors to be treated in one procedure Primary tumor either resected (primary first) or with a plan for curative treatment (liver first). Exclusion Criteria: • More than 3 lung metastases where 1 is >10mm, or 1 lung metastasis >15 mm (OR: unresectable lung metastases as decided by the lung MDT meeting) Presence of extrahepatic, extrapulmonary metastases. Surgical indication for removal of enlarged lymph nodes in the hepatic hilum. (Enlarged lymph nodes without indication of removal are not considered an exclusion criterium) Tumor closer than 10 mm to right/left main bile duct Suspected tumor infiltration to adjacent organs Progression (as of RECIST [18]) on 2nd line chemotherapy Previous inclusion in this trial Not eligible for workup according to study criteria Contraindication to contrast enhanced CT scan Manifest liver cirrhosis Pregnancy ECOG performance status ≥3 Simultaneous resection of primary tumor or any other concomitant surgical procedure Any other reason why, in the investigator's opinion, the patient should not be included.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Surgical resection<br>Liver resection | Procedure: Surgical resection<br>* Resection of metastasis<br>|
| Experimental: Thermal ablation<br>Thermal ablation (Microwave or radiofrequency) | Procedure: Thermal ablation<br>* Ablation of metastasis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local tumor progression | Local tumor progression at site of treatment | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival following treatment | 60 months | 
| Overall survival (secondary analysis) | A secondary analysis will be performed on a oncologically more homogenous group of patients that fulfil the following requirements: a) no previous surgical procedure on the liver, b) no extrahepatic metastases, and c) that had their primary tumor resected | 60 months | 
| Disease free survival | DFS | 60 months | 
| Postoperative complications | Morbidity | 30 days | 
| Health related quality of life | HRQoL is measured using SF-36 | 12 months | 
| Cost-Effectiveness | An analysis of cost will be performed to assess cost-effectiveness | 12 months | 
| Hemodynamic response | The hemodynamic response to the two interventions will be recorded and compared | 7 days | 
| Ventilation methods | The intraoperative movement of the liver will be measured using different ventilation methods (one lung ventilation, jet ventilation, gentle double lung ventilation). The movement of the liver during the different ventilation methods will be assessed in cm. | 1 day | 
| Cerebral flow | Intraoperative cerebral blood flow will be measured and related to cardiac output and other hemodynamic measures. Micro bubbles caused by the treatment will be visualized using ultrasonography. | 1 day | 
| Inflammatory response | The inflammatory response (cytokines, complement, catecholamines) will be compared. | 7 days |