Anatomical Resection VS. Nonanatomical Resection for Colorectal Liver Metastases With Gene Mutation or Right-sidedness

Study Overview
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Brief Summary
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In this study, colorectal cancer patients with initially resectable liver-only metastases, as prospectively confirmed by a local multidisciplinary team (MDT) according to predefined criteria, will be tested for RAS and BRAF tumor mutation status. Patients with gene mutant or right-sidedness will be randomised between anatomical resection (AR) or nonanatomical resection (NAR). The primary end-point is the relapse-free survival.

Detailed Description
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This study is a prospective, single-center, randomized control trial. The major including criteria are (1) Histologically confirmed colorectal cancer initially resectable liver-only metastases ; (2) patient has the opportunity to perform either anatomical resection (AR) or nonanatomical resection (NAR) surgery; (3) the number of metastasis is 1-3; (4) KRAS/NRAS/BRAF mutation or right-sidedness. Patients will be randomised between AR or NAR. Patients will be stratified for gene mutation and right-sidedness. Based upon the segmental anatomy of the liver according to Couinaud system, AR is defined as the resection of one or more complete hepatic segments in our study, including bisegmentectomy, right hemihepatectomy, left hemihepatectomy, extended right hemihepatectomy, extended left hemihepatectomy, single segmentectomy, caudate lobectomy, or a combination thereof. NAR, also called as wedge resection, is defined as the resection of the tumor with a margin of normal parenchyma regardless of the hepatic anatomy. The primary end-point is the relapse-free survival. The secondary end-points are postoperative complication, postoperative mortality, hospital length of stay, and overall survival.

Official Title
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Anatomical Resection Versus Nonanatomical Resection for Colorectal Liver Metastases Patients With Gene Mutation or Right-sidedness: The ARCLAMP Randomized Controlled Trial

Conditions
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Colorectal Carcinoma, Liver Metastases

Intervention / Treatment
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* Procedure: anatomical liver resection
* Procedure: nonanatomical liver resection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 and ≤ 75 years; Histological proof of colorectal adenocarcinoma; Resectable colorectal liver metastasis without detectable extrahepatic distant metastatic disease (determined by a local MDT); Suitable for anatomical or nonanatomical liver resection (determined by a local MDT); Number of metastasis is 1 to 3; KRAS/NRAS/BRAF mutation or right-sidedness; Performance Status (ECOG) 0 1; Adequate hematological function: Neutrophils≥1.5 x109/l and platelet count≥100 x109/l; Hb ≥9g/dl (within 1 week prior to randomization); Adequate liver and renal function: total bilirubin ≤2.0 mg/dl, serum transaminases ≤ 5x upper limit of normal(ULN), and serum creatinine ≤ 1.5x ULN and creatinine clearance ≥ 30 ml/min; Written informed consent. Exclusion Criteria: Previous systemic treatment for metastatic disease; Previous surgery for metastatic disease; Extrahepatic metastases; Unresectable primary tumor; Major cardiovascular events (myocardial infarction, severe/unstable angina, congestive heart failure, CVA) within 12 months before randomisation; Second primary malignancy within the past 5 years; Acute or subacute intestinal obstruction; Drug or alcohol abuse; No legal capacity or limited legal capacity; Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: anatomical resection group<br>Based upon the segmental anatomy of the liver according to Couinaud system, anatomical resection (AR) is defined as the resection of one or more complete hepatic segments in our study, including bisegmentectomy, right hemihepatectomy, left hemihepatectomy, extended right hemihepatectomy, extended left hemihepatectomy, single segmentectomy, caudate lobectomy, or a combination thereof. | Procedure: anatomical liver resection<br>* Based upon the segmental anatomy of the liver according to Couinaud system, anatomical resection (AR) was defined as resection of 1 or more complete hepatic segments in our study, including bisegmentectomy, right hemihepatectomy, left hemihepatectomy, extended right hemihepatectomy, extended left hemihepatectomy, single segmentectomy, caudate lobectomy, or a combination of these.<br>|
| Active Comparator: nonanatomical resection group<br>nonanatomical resection (NAR), also called as wedge resection, is defined as the resection of the tumor with a margin of normal parenchyma regardless of the hepatic anatomy. | Procedure: nonanatomical liver resection<br>* Nonanatomical resection(NAR), known as wedge resection, was defined as resection of the tumor with a margin of normal parenchyma without regard to hepatic anatomy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| relapse-free survival | The relapse-free survival (PFS) was defined as the period from the start of initial liver resection to the date of tumor relapse or death | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | The overall survival (OS) was defined as the period from the start of initial liver resection until death from any cause, at which point the data was censored. | 5 years | 
| postoperative hospital stay | The postoperative hospital stay is defined as the number of date from the first day after operation to discharge. | 30 days post operatively | 
| postoperative complication | Patients will be evaluated for surgical morbidity during 1 month. Postoperative morbidity will be scored according 'Clavien-Dindo Grade'. | After surgery during one month | 
| postoperative mortality | any death occured within 90 days after the last resection of primary and metastatic lesions | After surgery during 90 days |