Five Year Oncological Outcome After CME for Sigmoid Colon Cancer

Sponsor

Nordsjaellands Hospital (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03774134

Collaborator

Bispebjerg Hospital (Other), Herlev Hospital (Other), Hvidovre University Hospital (Other), Zealand University Hospital (Other)

920

Enrollment

190

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Study based in existing databases investigating the causal oncological treatment effects of complete mesocolic excision on UICC stage I-III sigmoid colon cancer

Condition or Disease	Intervention/Treatment	Phase
Sigmoid Neoplasms	Procedure: Complete mesocolic excision Procedure: Conventional colon resection

Detailed Description

Population-based cohort study, predominantly prospective based, on the same population as our previously study comparing short-term outcome after CME with conventional colon resections. The COMES database combines the prospectively registered colon cancer database in Hillerød (CME data), and data from the national database of the Danish Colorectal Cancer Group (DCCG) covering patients undergoing conventional resection (non-CME) in the other three centers. The medical records of all the patients in the non-CME group (control group) were reviewed by colorectal surgeons from Hillerød. Data audit for all CME patients was performed by various co-authors employed at the other centers. A similar audit of data for non-CME patients having postoperative complications or recurrence was performed by the co-author representing the department treating the specific patients. Follow-up data were registered prospectively in the medical records of the participating departments during patient follow-up.

Continuous data are presented as median and interquartile ranges, and categorical data as frequencies and proportions. Kruskal-Wallis test and Fisher's exact test were used as appropriate. Death is a competing risk to recurrence and time-to-event analyses were performed as competing risk analyses obtaining the cumulative incidences for recurrence or death using the "cmprsk" R-package.

Unbiased estimation of marginal or population-averaged treatment effects in observational and non-randomized studies can be obtained through different propensity score methods. Inverse Probability of Treatment Weighting (IPTW) uses the propensity score to weight each patient's data based on the inverse probability of receiving the treatment actually received. IPTW gives unbiased estimates of average treatment effects in time-to-event analyses if no differences in observed baseline covariates exist between the treatment groups. To account for baseline differences between patients in the two groups, stabilized weights truncated at the 0.99 interval were calculated using the "IPW" R-package. The following baseline covariates will be used: age, sex, ASA score, neoadjuvant chemotherapy, tumor morphology, perineural invasion, extramural venous invasion, tumor stage, and serosal invasion. All covariates used and UICC stage, two-way interactions, and squared terms of continuous covariates will be assessed for balance between the CME and the non-CME group after IPTW using the "cobalt" R-package. Absolute mean differences in mean (using standardized mean difference) and proportions (using raw mean difference) below 0.1, and variance ratios between 0.5 and 2 will be accepted. Graphical inspection of the distribution of covariates will be also performed.

The cause-specific hazards and overall survival will be analyzed using Cox regression. Binary outcomes were analyzed using logistic regression. Lymph node yield will be analyzed using linear regression after logarithmic transformation. Number of metastatic lymph nodes will be analyzed using negative binominal regression. All analyses of primary and secondary outcomes will be performed after IPTW. The 95% confidence intervals for the estimates from the original Cox regression IPTW analyses will be constructed after 1000 bootstraps with replacement, and a robust sandwich estimator will be used for the logistic regression analyses in order to ensure correct variance estimation.

All available data will be used. Model assumptions will be checked. A p-value below or equal to 0.05 will be considered significant. All analyses will be performed using R statistical software, version 3.5.1 (R Foundation for Statistical Computing, Vienna, Austria).

Study Design

Study Type:

Observational

Actual Enrollment :

920 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Five Year Oncological Outcome After Complete Mesocolic Excision for Sigmoid Colon Cancer: a Population-based Cohort Study

Actual Study Start Date :

Jun 1, 2008

Actual Primary Completion Date :

Jan 31, 2019

Anticipated Study Completion Date :

Mar 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
CME group The CME group consisted of patients, who underwent elective CME for sigmoid colon adenocarcinoma at Nordsjaellands Hospital Hillerød from 1 June 2008 to 31 December 2014.	Procedure: Complete mesocolic excision Based on the principles of CME. The inferior mesenteric artery (IMA) was divided at its origin from the aorta to perform central lymph nodes dissection along the IMA between the aorta and the branching of the left colic artery. Sigmoid resection included the complete sigmoid colon and resection of the upper part of the rectum to ensure sufficient perfusion of the colo-rectal anastomosis. To achieve sufficient distance at the proximal bowel resection margin, parts of the descending colon or even left hemicolectomy were performed at the surgeon's discretion.
Non-CME group The non-CME group comprised patients having a elective conventional colon cancer resection for sigmoid adenocarcinoma at the other three colorectal centers in the Capital Region of Denmark from 1 June 2008 to 31 December 2013.	Procedure: Conventional colon resection The patients underwent what was considered standard colon cancer resections in Denmark during the study period.

Arm

Intervention/Treatment

CME group

The CME group consisted of patients, who underwent elective CME for sigmoid colon adenocarcinoma at Nordsjaellands Hospital Hillerød from 1 June 2008 to 31 December 2014.

Procedure: Complete mesocolic excision

Based on the principles of CME. The inferior mesenteric artery (IMA) was divided at its origin from the aorta to perform central lymph nodes dissection along the IMA between the aorta and the branching of the left colic artery. Sigmoid resection included the complete sigmoid colon and resection of the upper part of the rectum to ensure sufficient perfusion of the colo-rectal anastomosis. To achieve sufficient distance at the proximal bowel resection margin, parts of the descending colon or even left hemicolectomy were performed at the surgeon's discretion.

Non-CME group

The non-CME group comprised patients having a elective conventional colon cancer resection for sigmoid adenocarcinoma at the other three colorectal centers in the Capital Region of Denmark from 1 June 2008 to 31 December 2013.

Procedure: Conventional colon resection

The patients underwent what was considered standard colon cancer resections in Denmark during the study period.

Outcome Measures

Primary Outcome Measures

Risk of recurrence [5.2 years]
Recurrence diagnosed by CT or positron emission tomography (PET)/CT of thorax and abdomen, chest radiograph and contrast-enhanced ultrasound of the liver, or laparotomy in case of suspicion of recurrence. Histological - Page 4 of 6 - verification of radiological findings of metastases during follow-up is not needed if the local multidisciplinary team conference deemed the finding as a recurrence. Metachronous colon tumors diagnosed during follow-up are considered as recurrences only if located in the anastomosis and with the same morphology as the primary tumor.

Secondary Outcome Measures

Overall survival [5.2 years]
Death by any cause
Short-term mortality [30 and 90 days]
Death from any cause within 30 and 90 days
Rate of postoperative complications [60 days]
Patients having surgical and non-surgical postoperative complications and with complications with Clavien-Dindo score of 3b or more
Mesocolic lymph nodes yield [1 day]
Median number of lymph nodes detected in the specimens and proportion of specimens with 22 or more lymph nodes detected

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Sigmoid colon cancer was defined as primary adenocarcinomas located in the sigmoid colon (more than 15 cm from the anal verge)
UICC stage I-III

Exclusion Criteria:

Synchronous colorectal cancer - even in the sigmoid colon
No residual tumor in the specimen after neoadjuvant chemotherapy
Metachronous colorectal cancer
Resections in Hillerød not performed according to the principles of CME
Non-macroradical (R2) resections (peroperative assessment)

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Nordsjaellands Hospital
Bispebjerg Hospital
Herlev Hospital
Hvidovre University Hospital
Zealand University Hospital

Investigators

Study Chair: Claus A Bertelsen, PhD, MD, Department of Surgery, Nordsjaellands Hospital Hillerød

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Nordsjaellands Hospital

ClinicalTrials.gov Identifier:

NCT03774134

Other Study ID Numbers:

CMELoS2019

First Posted:

Dec 12, 2018

Last Update Posted:

Apr 26, 2022

Last Verified:

Apr 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Nordsjaellands Hospital

Additional relevant MeSH terms:

Colonic Neoplasms

Sigmoid Neoplasms

Study Results

No Results Posted as of Apr 26, 2022