Predictive Value of DNA Mismatch Repair System in Colorectal Cancers (DNAMMR)

May 22, 2023 updated by: Gennaro Galizia, University of Campania "Luigi Vanvitelli"

Assessment of the DNA Mismatch Repair System is Crucial in Colorectal Cancers Necessitating Adjuvant Treatment: a Propensity Score-matched and Win Ratio Analysis

  • Microsatellite instable (MSI) tumors represent almost the 15% of all sporadic colorectal cancers (CRCs).
  • Literature data show that this unique tumor population appears to be poorly responsive to conventional chemotherapy and conversely reveals excellent results to immunotherapy.
  • Our data, as demonstrated by propensity score-matched and win ratio analysis, show that there are no substantial differences between MSI and MSS tumors in early CRC stages treated with surgery alone.
  • On the contrary, stable tumors (MSS) did much better than MSI tumors in advanced CRC stages undergoing conventional adjuvant treatment.
  • Determination of status of DNA mismatch repair system is crucial in high-risk CRCs to optimize treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Colorectal cancers (CRCs) with deficient DNA mismatch repair (MMR) system (so called dMMR or MSI tumors) represent a no-negligible part of sporadic CRCs. Prognostic value of this unique cell population remains controversial, but undoubtedly these tumors are characterized by poor response to conventional chemotherapy, an high tumor mutational burden resulting in a brisk immuno response, and, as recently observed, excellent results to the immunotherapy. The aim of this study was to evaluate, by using sophisticated statistical analyses, the predictive value of MSI status and its optimal treatment.

A series of 403 consecutive CRC patients treated by the same oncological team from 2014 to 2021 entered the study. No patients underwent immunotherapy. Immunohistochemistry, integrated by polymerase chain reaction if appropriate, was used to categorize specimens in microsatellite stable (MSS) and instable (MSI) tumors. The win ratio (WR) approach was utilized to compare composite outcomes of MSS and MSI tumors while controlling for radical versus no radical resection, propensity score-matched analysis, and reversing primary endpoint.

Study Type

Observational

Enrollment (Actual)

403

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

CRC patients undergoing surgery

Description

Inclusion Criteria:

  • all consecutive CRC patients observed from January 2014 to December 2021

Exclusion Criteria:

  • Patients with suspected or confirmed Lynch's syndrome (12 patients) and rectal cancers (98 patients) undergoing neoadjuvant treatment

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
group 1 or MSS
colorectal cancers (CRCs) with stable microsatellite
Procedure: colorectal resection
potential resective surgery
group 2 or MSI
colorectal cancers (CRCs) with unstable microsatellite
Procedure: colorectal resection
potential resective surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
survival rate
Time Frame: "From date of surgical operation until the date of death from any cause assessed up to 60 months"
overall survival
"From date of surgical operation until the date of death from any cause assessed up to 60 months"

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
recurrence rate
Time Frame: "From date of surgical operation until the date of documented tumor recurrence assessed up to 60 months"
disease-free survival
"From date of surgical operation until the date of documented tumor recurrence assessed up to 60 months"

Collaborators and Investigators

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

Sponsor

University of Campania "Luigi Vanvitelli"

Investigators

  • Study Director: Gennaro Galizia, MD, University of Campania 'Luigi Vanvitelli'

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)

January 1, 2014

Primary Completion (Actual)

December 31, 2021

Study Completion (Actual)

March 31, 2023

Study Registration Dates

First Submitted

May 4, 2023

First Submitted That Met QC Criteria

May 12, 2023

First Posted (Actual)

May 23, 2023

Study Record Updates

Last Update Posted (Actual)

May 24, 2023

Last Update Submitted That Met QC Criteria

May 22, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Università Vanvitelli Napoli

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All data will be made available by contacting the principal investigator

IPD Sharing Time Frame

data will become available after conclusion of the trial and publication of the results. After that data will be available for two years.

IPD Sharing Access Criteria

gennaro.galizia@unicampania.it

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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