Five Year Oncological Outcome After CME for Sigmoid Colon Cancer

NCT ID: NCT03774134

Last Updated: 2024-06-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

920 participants

Study Classification

OBSERVATIONAL

Study Start Date

2008-06-01

Study Completion Date

2025-12-31

Brief Summary

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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

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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).

Conditions

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Sigmoid Neoplasms

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

Complete mesocolic excision

Intervention Type PROCEDURE

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.

Conventional colon resection

Intervention Type PROCEDURE

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

Interventions

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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.

Intervention Type PROCEDURE

Conventional colon resection

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

Intervention Type PROCEDURE

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bispebjerg Hospital

OTHER

Sponsor Role collaborator

Herlev Hospital

OTHER

Sponsor Role collaborator

Hvidovre University Hospital

OTHER

Sponsor Role collaborator

Zealand University Hospital

OTHER

Sponsor Role collaborator

Nordsjaellands Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Claus A Bertelsen, PhD, MD

Role: STUDY_CHAIR

Department of Surgery, Nordsjaellands Hospital Hillerød

References

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Rosenberg J, Fischer A, Haglind E; Scandinavian Surgical Outcomes Research Group. Current controversies in colorectal surgery: the way to resolve uncertainty and move forward. Colorectal Dis. 2012 Mar;14(3):266-9. doi: 10.1111/j.1463-1318.2011.02896.x.

Reference Type BACKGROUND
PMID: 22122825 (View on PubMed)

West NP, Sutton KM, Ingeholm P, Hagemann-Madsen RH, Hohenberger W, Quirke P. Improving the quality of colon cancer surgery through a surgical education program. Dis Colon Rectum. 2010 Dec;53(12):1594-603. doi: 10.1007/DCR.0b013e3181f433e3.

Reference Type BACKGROUND
PMID: 21178852 (View on PubMed)

Hohenberger W, Weber K, Matzel K, Papadopoulos T, Merkel S. Standardized surgery for colonic cancer: complete mesocolic excision and central ligation--technical notes and outcome. Colorectal Dis. 2009 May;11(4):354-64; discussion 364-5. doi: 10.1111/j.1463-1318.2008.01735.x. Epub 2009 Nov 5.

Reference Type BACKGROUND
PMID: 19016817 (View on PubMed)

Bokey L, Chapuis PH, Chan C, Stewart P, Rickard MJ, Keshava A, Dent OF. Long-term results following an anatomically based surgical technique for resection of colon cancer: a comparison with results from complete mesocolic excision. Colorectal Dis. 2016 Jul;18(7):676-83. doi: 10.1111/codi.13159.

Reference Type BACKGROUND
PMID: 26476136 (View on PubMed)

Bertelsen CA, Neuenschwander AU, Jansen JE, Wilhelmsen M, Kirkegaard-Klitbo A, Tenma JR, Bols B, Ingeholm P, Rasmussen LA, Jepsen LV, Iversen ER, Kristensen B, Gogenur I; Danish Colorectal Cancer Group. Disease-free survival after complete mesocolic excision compared with conventional colon cancer surgery: a retrospective, population-based study. Lancet Oncol. 2015 Feb;16(2):161-8. doi: 10.1016/S1470-2045(14)71168-4. Epub 2014 Dec 31.

Reference Type BACKGROUND
PMID: 25555421 (View on PubMed)

Kotake K, Mizuguchi T, Moritani K, Wada O, Ozawa H, Oki I, Sugihara K. Impact of D3 lymph node dissection on survival for patients with T3 and T4 colon cancer. Int J Colorectal Dis. 2014 Jul;29(7):847-52. doi: 10.1007/s00384-014-1885-z. Epub 2014 May 6.

Reference Type BACKGROUND
PMID: 24798631 (View on PubMed)

Olofsson F, Buchwald P, Elmstahl S, Syk I. High Tie or not in Resection for Cancer in the Sigmoid Colon? Scand J Surg. 2019 Sep;108(3):227-232. doi: 10.1177/1457496918812198. Epub 2018 Nov 21.

Reference Type BACKGROUND
PMID: 30458672 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26780563 (View on PubMed)

Austin PC. An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies. Multivariate Behav Res. 2011 May;46(3):399-424. doi: 10.1080/00273171.2011.568786. Epub 2011 Jun 8.

Reference Type BACKGROUND
PMID: 21818162 (View on PubMed)

Austin PC, Stuart EA. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med. 2015 Dec 10;34(28):3661-79. doi: 10.1002/sim.6607. Epub 2015 Aug 3.

Reference Type BACKGROUND
PMID: 26238958 (View on PubMed)

Other Identifiers

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CMELoS2019

Identifier Type: -

Identifier Source: org_study_id

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