DNAMMR: Predictive Value of DNA Mismatch Repair System in Colorectal Cancers

Sponsor

University of Campania "Luigi Vanvitelli" (Other)

Overall Status

Completed

CT.gov ID

NCT05871567

Collaborator

(none)

403

Enrollment

110.9

Actual Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
MSI-H Colorectal Cancer	Procedure: colorectal resection

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 Design

Study Type:

Observational [Patient Registry]

Actual Enrollment :

403 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Jan 1, 2014

Actual Primary Completion Date :

Dec 31, 2021

Actual Study Completion Date :

Mar 31, 2023

Arms and Interventions

Arm	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

Arm

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

Outcome Measures

Primary Outcome Measures

survival rate ["From date of surgical operation until the date of death from any cause assessed up to 60 months"]
overall survival

Secondary Outcome Measures

recurrence rate ["From date of surgical operation until the date of documented tumor recurrence assessed up to 60 months"]
disease-free survival

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 86 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

University of Campania "Luigi Vanvitelli"

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Gennaro Galizia, Full Professor of Surgery, University of Campania "Luigi Vanvitelli"

ClinicalTrials.gov Identifier:

NCT05871567

Other Study ID Numbers:

Università Vanvitelli Napoli

First Posted:

May 23, 2023

Last Update Posted:

May 24, 2023

Last Verified:

May 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Gennaro Galizia, Full Professor of Surgery, University of Campania "Luigi Vanvitelli"

Colorectal cancers;

DNA mismatch repair;

Win ratio

Additional relevant MeSH terms:

Colorectal Neoplasms

Study Results

No Results Posted as of May 24, 2023