Radiological Markers in Locally Advanced Rectal Cancer (LARC)

February 21, 2025 updated by: Francesco De Cobelli, IRCCS San Raffaele
The goal of this observational study is to evaluate the prognostic significance of radiological markers, including the Likert Score derived from diffusion-weighted MRI (DWI), in patients with locally advanced rectal cancer (LARC) treated with total neoadjuvant therapy (TNT). Specifically, the study investigates the association between the Likert Score on restaging MRI and key clinical outcomes, such as overall survival (OS) and time to progression (TTP). Furthermore, it examines the impact of other MRI-derived markers-extramural venous invasion (EMVI), tumor deposits (TDs), and mesorectal fascia invasion (MFI)-on disease progression and patient prognosis. This study retrospectively analyzes 179 patients who underwent TNT followed by surgery between 2009 and 2022. Participants were required to have pre- and post-treatment MRI scans. MRI imaging data and patient outcomes, including overall survival (OS) and time to progression (TTP), will be analyzed over a follow-up period extending until July 31, 2024. Findings from this study may help refine MRI-based prognostic tools for personalized treatment strategies in rectal cancer.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

This study investigates the prognostic role of diffusion-weighted MRI (DWI), using the Likert Score and other radiological markers, in patients with locally advanced rectal cancer (LARC) undergoing total neoadjuvant therapy (TNT) followed by radical surgery. The study cohort consists of 179 patients who received TNT between 2009 and 2022 at our institution. Inclusion criteria required patients to have biopsy-confirmed stage II-III LARC, available MRI at both staging and restaging time points, and completion of the TNT protocol.

The TNT regimen included up to three cycles of modified XELOX chemotherapy (oxaliplatin and capecitabine), with the first cycle administered as induction chemotherapy and the remaining two cycles administered concurrently with radiotherapy (total dose: 46.2 Gy in 18 fractions). Surgical resection was performed at a median of 11 weeks post-radiotherapy, with adjuvant chemotherapy administered based on histopathology findings.

MRI acquisition was standardized using a 1.5-T scanner, with DWI sequences applied to assess key prognostic markers, including extramural venous invasion (EMVI), tumor deposits (TDs), and mesorectal fascia invasion (MFI). The Likert Score, a five-point grading system based on DWI findings, was applied to restaging MRI to stratify treatment response, with scores of 0-2 indicating a favorable response and 3-4 indicating a poor response.

The study's primary objective is to evaluate the impact of the Likert Score on overall survival (OS) and time to progression (TTP). Secondary objectives include assessing the prognostic significance of EMVI, TDs, and MFI in predicting OS and TTP. The statistical analysis will include Kaplan-Meier survival curves to estimate OS and TTP, stratified according to the presence/score of radiological markers, Cox proportional hazards regression to assess the impact of prognostic factors on survival outcomes, Fisher's exact test to evaluate associations between categorical variables, and Cohen's Kappa to measure interobserver agreement in MRI assessments..

This study aims to refine MRI-based prognostic assessment tools to enhance personalized treatment strategies for rectal cancer. Findings from this research may support the integration of DWI-based Likert Score evaluation into clinical practice to improve risk stratification and treatment decision-making in patients with LARC undergoing TNT. The follow-up period extends until July 31, 2024, ensuring a comprehensive analysis of long-term outcomes.

Study Type

Observational

Enrollment (Estimated)

179

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy, 20132
        • Department of Radiology, IRCCS Ospedale San Raffaele
        • Contact:
        • Contact:
        • Contact:
          • Francesco De Cobelli, MD

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

The study includes patients with locally advanced rectal cancer (LARC) who underwent total neoadjuvant therapy (TNT) followed by surgery at our institution between 2009 and 2022. MRI imaging was performed both at initial staging and after TNT before surgery. The follow-up period extends until July 31, 2024, with survival outcomes being analyzed retrospectively.

Description

Inclusion Criteria:

  • Risonanza Magnetica informed consent signed
  • All patients that received total neoadjuvant therapy (TNT) (chemo/radiotherapy followed by surgery), between 2009 and 2022 at our institution
  • Staging and re-staging MRI available

Exclusion Criteria:

  • Staging and re-staging MRI not available

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time To Progression (TTP) Stratified by Likert Score
Time Frame: 5 years
TTP will be measured as the time from diagnosis to disease progression, as assessed through clinical, radiological, or pathological criteria. Patients will be stratified based on the Likert Score derived from diffusion-weighted MRI (DWI) at restaging. Kaplan-Meier survival curves will be used to estimate progression-free probabilities, with comparisons between groups performed using the log-rank test. Cox proportional hazards regression will be used to evaluate the prognostic significance of the Likert Score. TTP will be measured in months, defined as the time from diagnosis to documented disease progression based on clinical, radiological, or pathological criteria.
5 years
Overall Survival (OS) Stratified by Likert Score
Time Frame: 5 years
OS will be measured as the time from diagnosis to death from any cause in patients with locally advanced rectal cancer (LARC) treated with total neoadjuvant therapy (TNT). Patients will be stratified based on the Likert Score derived from diffusion-weighted MRI (DWI) at restaging. Kaplan-Meier survival curves will be used to estimate survival probabilities, and differences between groups will be compared using the log-rank test. Cox proportional hazards regression will be performed to assess the prognostic value of the Likert Score. OS will be measured in months, defined as the time from diagnosis to death. Patients alive at the end of the study period or lost to follow-up will be censored at their last recorded visit.
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prognostic Value of EMVI Score on Time to Progression (TTP)
Time Frame: 5 years
The study will evaluate the impact of extramural venous invasion (EMVI) on time to progression (TTP) in patients with locally advanced rectal cancer (LARC) undergoing total neoadjuvant therapy (TNT). TTP, measured in months, will be defined as the time from diagnosis to documented disease progression based on clinical, radiological, or pathological criteria. Patients will be stratified by EMVI Score, assessed on staging MRI. Progression-free probabilities will be estimated using Kaplan-Meier survival curves, with group comparisons performed via the log-rank test. The prognostic value of the EMVI Score will be examined through Cox proportional hazards regression.
5 years
Prognostic Value of Tumor Deposits on Time to Progression (TTP)
Time Frame: 5 years
The study will evaluate the impact of tumor deposits (TDs) on time to progression (TTP) in patients with locally advanced rectal cancer (LARC) undergoing total neoadjuvant therapy (TNT). TTP, measured in months, will be defined as the time from diagnosis to documented disease progression based on clinical, radiological, or pathological criteria. Patients will be stratified based on the presence of TDs, identified on staging MRI. Progression-free probabilities will be estimated using Kaplan-Meier survival curves, with group comparisons performed via the log-rank test. The prognostic significance of TDs will be analyzed using Cox proportional hazards regression.
5 years
Prognostic Value of Mesorectal Fascia Infiltration on Time to Progression (TTP)
Time Frame: 5 years
The study will evaluate the impact of mesorectal fascia infiltration (MFI) on time to progression (TTP) in patients with locally advanced rectal cancer (LARC) undergoing total neoadjuvant therapy (TNT). TTP, measured in months, will be defined as the time from diagnosis to documented disease progression based on clinical, radiological, or pathological criteria. Patients will be stratified based on the presence of MFI, identified on staging MRI. Progression-free probabilities will be estimated using Kaplan-Meier survival curves, with group comparisons performed via the log-rank test. The prognostic significance of MFI will be analyzed using Cox proportional hazards regression.
5 years
Prognostic Value of EMVI Score on Overall Survival (OS)
Time Frame: 5 years
The study will evaluate the impact of the EMVI Score on OS in patients with locally advanced rectal cancer (LARC) undergoing total neoadjuvant therapy (TNT). OS, measured in months, will be defined as the time from diagnosis to death. Patients will be stratified by EMVI Score, assessed on staging MRI. Survival probabilities will be estimated using Kaplan-Meier curves, with group comparisons performed via the log-rank test. The prognostic significance of the EMVI Score will be analyzed using Cox proportional hazards regression.
5 years
Prognostic Value of Tumor Deposits on Overall Survival (OS)
Time Frame: 5 years
The study will evaluate the impact of tumor deposits (TDs) on OS in patients with locally advanced rectal cancer (LARC) undergoing total neoadjuvant therapy (TNT). OS, measured in months, will be defined as the time from diagnosis to death. Patients will be stratified based on the presence of TDs, identified on staging MRI. Survival probabilities will be estimated using Kaplan-Meier curves, with group comparisons performed via the log-rank test. The prognostic significance of TDs will be analyzed using Cox proportional hazards regression.
5 years
Prognostic Value of Mesorectal Fascia Infiltration on Overall Survival (OS)
Time Frame: 5 years
The study will evaluate the impact of mesorectal fascia infiltration (MFI) on OS in patients with locally advanced rectal cancer (LARC) undergoing total neoadjuvant therapy (TNT). OS, measured in months, will be defined as the time from diagnosis to death. Patients will be stratified based on the presence of MFI, assesed on staging MRI. Survival probabilities will be estimated using Kaplan-Meier curves, with group comparisons performed via the log-rank test. The prognostic significance of MFI will be analyzed using Cox proportional hazards regression.
5 years

Collaborators and Investigators

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

Sponsor

IRCCS San Raffaele

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 (Estimated)

March 1, 2025

Primary Completion (Estimated)

July 31, 2025

Study Completion (Estimated)

August 15, 2025

Study Registration Dates

First Submitted

February 18, 2025

First Submitted That Met QC Criteria

February 21, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 21, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LARC Protocol

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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