Clinical trial NCT03774134: Five Year Oncological Outcome After CME for Sigmoid Colon Cancer
Official title: Five Year Oncological Outcome After Complete Mesocolic Excision for Sigmoid Colon Cancer: a Population-based Cohort Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Sigmoid Neoplasms
Keywords: Colon cancer
Surgery
Oncological outcome
Survival
Lead sponsor: Nordsjaellands Hospital
Sponsor class: OTHER
Collaborators: name: Bispebjerg Hospital
name: Herlev Hospital
name: Hvidovre University Hospital
name: Zealand University Hospital
First posted: 2018-12-12
Enrollment: 920
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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

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).

Eligibility criteria: 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)

Primary outcomes:
measure: Risk of recurrence
timeFrame: 5.2 years
Secondary outcomes:
measure: Overall survival
timeFrame: 5.2 years
measure: Short-term mortality
timeFrame: 30 and 90 days
measure: Rate of postoperative complications
timeFrame: 60 days
measure: Mesocolic lymph nodes yield
timeFrame: 1 day
Other outcomes:
Locations:
Study officials:
affiliation: Department of Surgery, Nordsjaellands Hospital Hillerød
name: Claus A Bertelsen, PhD, MD
role: STUDY_CHAIR
References:
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citation: Bertelsen CA, Neuenschwander AU, Jansen JE, Kirkegaard-Klitbo A, Tenma JR, Wilhelmsen M, Rasmussen LA, Jepsen LV, Kristensen B, Gogenur I; Copenhagen Complete Mesocolic Excision Study (COMES); Danish Colorectal Cancer Group (DCCG). Short-term outcomes after complete mesocolic excision compared with 'conventional' colonic cancer surgery. Br J Surg. 2016 Apr;103(5):581-9. doi: 10.1002/bjs.10083. Epub 2016 Jan 18.
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