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Predictive Value of DNA Mismatch Repair System in Colorectal Cancers

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

Status
Completed
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT05871567
Acronym
DNAMMR
Enrollment
403
Registered
2023-05-23
Start date
2014-01-01
Completion date
2023-03-31
Last updated
2023-05-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

MSI-H Colorectal Cancer

Keywords

Colorectal cancers;, DNA mismatch repair;, Win ratio

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.

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.

Interventions

potential resective surgery

Sponsors

University of Campania Luigi Vanvitelli
Lead SponsorOTHER

Study design

Observational model
COHORT
Time perspective
PROSPECTIVE

Eligibility

Sex/Gender
ALL
Age
18 Years to 86 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
survival rateFrom date of surgical operation until the date of death from any cause assessed up to 60 monthsoverall survival

Secondary

MeasureTime frameDescription
recurrence rateFrom date of surgical operation until the date of documented tumor recurrence assessed up to 60 monthsdisease-free survival

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026