Five Year Oncological Outcome After CME for Right-sided Colon Cancer

March 11, 2019 updated by: Claus Anders Bertelsen, PhD, MD, Nordsjaellands Hospital

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

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

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Population-based cohort study, predominantly prospective based, on the same population as the investigator's 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.

Statistical analysis plan

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 location, 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, variance ratios between 0.5 and 2, and Kolmogorov-Smirnov tests equal or below 0.05 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 will be 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 Type

Observational

Enrollment (Actual)

1069

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Data for all patients undergoing elective surgery for UICC stage I-III colonic adenocarcinoma in the Capital Region of Denmark. The population of this region is approximately 1⋅75 million, more than 30 per cent of the population of Denmark, and it is served by only four public university colorectal cancer centres.

Description

Inclusion Criteria:

  • Right-sided colon cancer was defined as primary adenocarcinomas located in the cecum, ascending colon hepatic flexure, right or mid third of the transverse colon.
  • UICC stage I-III - Gastroepiploic and infrapyloric lymph node metastases are not considered as distant metastases

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
CME group
The CME group consisted of patients, who underwent elective CME for right-sided colon adenocarcinoma at Nordsjaellands Hospital Hillerød from 1 June 2008 to 31 December 2013.
Procedure: Complete mesocolic excision
The resection was based on the principles of CME. The superior mesenteric vein was exposed to perform central vessel ligation and lymph nodes dissection. Extended right hemicolectomies for tumors located from the ascending colon close to the hepatic flexure and distally were performed openly as standard during the study period. These resections included the prepyloric and gastroepiploic lymph nodes dissection.
Non-CME group
The non-CME group comprised patients having a elective conventional colon cancer resection for right-sided adenocarcinoma at the other three colorectal centers in the Capital Region of Denmark from 1 June 2008 to 31 December 2013.
Procedure: Conventional colon resections
The patients underwent what was considered standard colon cancer resections in Denmark during the study period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Risk of recurrence
Time Frame: 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 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.
5.2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 5.2 years
Death by any cause
5.2 years
Short-term mortality
Time Frame: 30 and 90 days
Death from any cause within 30 and 90 days
30 and 90 days
Rate of postoperative complications
Time Frame: 60 days
Patients having surgical and non-surgical postoperative complications and with complications with Clavien-Dindo score of 3b or more
60 days
Number of mesocolic lymph nodes
Time Frame: 1 day
Median number and specimens with 22 or more lymph nodes detected
1 day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nordsjaellands Hospital

Collaborators

Zealand University Hospital
Hvidovre University Hospital
Bispebjerg Hospital
Herlev Hospital

Investigators

  • Principal Investigator: Claus A Bertelsen, PhD, MD, Nordsjaellands Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2008

Primary Completion (Actual)

January 31, 2019

Study Completion (Anticipated)

March 16, 2019

Study Registration Dates

First Submitted

November 22, 2018

First Submitted That Met QC Criteria

November 26, 2018

First Posted (Actual)

November 27, 2018

Study Record Updates

Last Update Posted (Actual)

March 13, 2019

Last Update Submitted That Met QC Criteria

March 11, 2019

Last Verified

December 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CMELoR2019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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