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

NCT ID: NCT03754075

Last Updated: 2019-03-13

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

UNKNOWN

Total Enrollment

1069 participants

Study Classification

OBSERVATIONAL

Study Start Date

2008-06-01

Study Completion Date

2019-03-16

Brief Summary

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

Detailed Description

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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).

Conditions

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Colonic 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 right-sided colon adenocarcinoma at Nordsjaellands Hospital Hillerød from 1 June 2008 to 31 December 2013.

Complete mesocolic excision

Intervention Type PROCEDURE

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.

Conventional colon resections

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

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.

Intervention Type PROCEDURE

Conventional colon resections

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

* 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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bispebjerg Hospital

OTHER

Sponsor Role collaborator

Hvidovre University Hospital

OTHER

Sponsor Role collaborator

Herlev Hospital

OTHER

Sponsor Role collaborator

Zealand University Hospital

OTHER

Sponsor Role collaborator

Nordsjaellands Hospital

OTHER

Sponsor Role lead

Responsible Party

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Claus Anders Bertelsen, PhD, MD

Consultant Colorectal Surgeon, Head of Research

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Claus A Bertelsen, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Nordsjaellands Hospital

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)

Lee L, Erkan A, Alhassan N, Kelly JJ, Nassif GJ, Albert MR, Rt Monson J. Lower survival after right-sided versus left-sided colon cancers: Is an extended lymphadenectomy the answer? Surg Oncol. 2018 Sep;27(3):449-455. doi: 10.1016/j.suronc.2018.05.031. Epub 2018 May 29.

Reference Type BACKGROUND
PMID: 30217301 (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)

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)

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)

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)

Wal WM van der, Geskus RB. ipw : An R Package for Inverse Probability Weighting. J Stat Softw 43(13):1-23, 2011.

Reference Type BACKGROUND

Bernhoff R. Colon cancer aspects on surgical treatment and complete mesocolic excision. PhD thesis. Stockholm 2018. ISBN 978-91-7676-919-5.

Reference Type BACKGROUND

Bertelsen CA, Neuenschwander AU, Jansen JE, Tenma JR, Wilhelmsen M, Kirkegaard-Klitbo A, Iversen ER, Bols B, Ingeholm P, Rasmussen LA, Jepsen LV, Born PW, Kristensen B, Kleif J. 5-year outcome after complete mesocolic excision for right-sided colon cancer: a population-based cohort study. Lancet Oncol. 2019 Nov;20(11):1556-1565. doi: 10.1016/S1470-2045(19)30485-1. Epub 2019 Sep 13.

Reference Type DERIVED
PMID: 31526695 (View on PubMed)

Other Identifiers

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CMELoR2019

Identifier Type: -

Identifier Source: org_study_id

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