Metabolomic Phenotyping After Surgery for Colon Cancer: Study of Novel Predictive Biomarkers

Study Overview
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Brief Summary
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Predictive biomarkers are needed to identify those patients with higher risk of recurrence after surgery for colon cancer with curative intent. Our main objective is to determine a metabolite profile in blood plasma from patients operated from colorectal cancer that can be associated with the oncologic outcome and be validated as predictive biomarkers in future studies. A secondary objective is to study the glycolytic metabolism of colon cancer cell lines treated with plasma samples from the same patients. In particular, to validate the increased utilization of lactate by tumor cells as a metabolic substrate using postoperative human samples. Patients with colorectal cancer that have undergone surgical resection will be included. Plasma samples will be obtained before surgery and the 4th day and the 3rd, 6th, 12th, and 18th months after surgery. Metabolic profiles in plasma samples will be determined using a kit that allows the quantification of 180 metabolites by mass spectrometry. A clinical follow up will be maintained for at least 2 years to identify tumor recurrences.

Detailed Description
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Up to 30-40% of patients operated from colorectal cancer display tumor recurrence. Predictive biomarkers are needed to identify those patients with higher risk of recurrence. Our main objective is to determine a metabolite profile in blood plasma from patients operated from colorectal cancer that can be associated with the oncologic outcome and be validated as prognostic biomarkers in future studies. A secondary objective is to study the glycolytic metabolism of colon cancer cell lines treated with plasma samples from the same patients. In particular, to validate the increased utilization of lactate by tumor cells as a metabolic substrate using postoperative human samples, as it was previously observed by us in vitro using an inflammatory environment in conditions of hypoxia and lack of glucose. Patients with colorectal cancer that have undergone surgical resection will be included. Plasma samples will be obtained before surgery and the 4th day and the 3rd, 6th, 12th, and 18th months after surgery. Metabolic profiles in plasma samples will be determined using a kit that allows the quantification of 180 metabolites by mass spectrometry. Cellular assays will be performed on the SW620 and HT-29 colon cancer cell lines. Cells will be treated with plasma samples and the concentration of lactate and other metabolites will be analyzed in the medium supernatants. A clinical follow up will be maintained for at least 2 years to identify tumor recurrences.

Official Title
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Metabolomic Phenotyping After Surgery for Colon Cancer: Study of Novel Predictive Biomarkers

Conditions
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Colon Cancer

Intervention / Treatment
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* Procedure: Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-metastatic colon and rectal cancer undergoing surgery with curative intent Patients signed informed consent Exclusion Criteria: Patients undergoing preoperative chemotherapy and/or radiotherapy Emergency surgery Surgical resection R1 or R2 Patients presenting with other known malignancies for which they are receiving treatment

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Non metastatic colon cancer patients<br>Consecutive patients undergoing elective surgery for non-metastatic colon or rectal cancer with curative intent. | Procedure: Surgery<br>* Segmental resection for colon cancer and anterior resection in patients with rectal cancer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival | Time from the date of surgery to the date of first documentation of recurrence | 5 years from the date of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-specific survival | Time from the date of surgery to death by colon cancer | 5 years from the date of surgery | 
| Local recurrence | Tumor associated with surgical site (anastomosis, tumor bed, and mesentery) and confirmed histologically or by imaging. | 5 years from the date of surgery | 
| Systemic recurrence | Spread of the disease outside the surgical field to organs such as the liver, lungs, bones, or brain | 5 years from the date of surgery | 
| Postoperative intra-abdominal sepsis | Anastomotic leak or intra-abdominal abscess | 30 days from the date of surgery | 
| Postoperative mortality |  | 30 days from the date of surgery |