Ploidy and Stroma in Early Rectal Cancer

March 9, 2022 updated by: Chris Cunningham, Oxford University Hospitals NHS Trust

An Observational Study to Correlate the Results of Ploidy and Stroma Analysis With Prognosis in Early Rectal Cancer

Early rectal cancer can be removed by minimally-invasive surgery, and the standard pathological assessment of the removed tumour gives valuable information about how advanced the tumour is. This gives an indication of how likely the cancer is to recur, so doctors and patient can decide on the most appropriate further treatment and follow-up. However there is still much uncertainty in these predictions about recurrence. This study will assess two further pathology tests, ploidy and stroma ratio in the tumour, by correlating the results with outcome. This will determine whether these two tests provide additional value in predicting outcome. If so, clinicians would be better able to advise patients with early rectal cancer about their prognosis and further management.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Early rectal cancer can be removed by minimally-invasive surgery, and the standard pathological assessment of the removed tumour gives valuable information about how advanced the tumour is. This information is very important in indicating whether the cancer is likely to recur, and therefore in advising the patient after surgery whether further treatment is advisable, and if not, what is the most appropriate follow-up regime. However there is still a lot of uncertainty in these predictions about recurrence of the cancer, and better tests are being sought. This study aims to look at two further pathology tests, ploidy and stroma ratio in the tumour, and correlate these test results with outcome in patients who have had an early rectal cancer removed. This will allow the investigators to assess whether these two tests provide additional value in predicting outcome. If so, clinicians would be better able to advise patients with early rectal cancer about their prognosis and further management.

Routine histopathology analysis of a rectal cancer specimen removed at surgery includes assessment of tumour size, depth of invasion, vascular, lymphatic and perineural invasion, tumour involvement of resection margins and nodal involvement. This information is valuable in predicting outcome. For example, predicted rates of local recurrence at 36 months following local excision of rectal cancer by transanal endoscopic microsurgery (TEM) based on tumour size, depth of invasion and lymphatic invasion have been tabulated. However such models are not perfect, and leave room for improvement. Ploidy and stroma ratio are two further tests which have shown some promise in predicting outcome.

Ploidy refers to the number of sets of chromosomes in a cell nucleus. Most human cells are normally diploid, with two sets of 23 chromosomes. Abnormal tumour cells may have a different number of sets of chromosomes, or be aneuploid, having some replicated or deleted chromosomes. In general, aneuploidy in cancer cells is associated with a worse prognosis. An early study of DNA ploidy in rectal cancer using flow cytometry showed an independent but small predictive effective of aneuploidy on survival. Technological advances now allow more accurate and detailed assessment of ploidy. The DNA ploidy status of tumour cells in early ovarian cancer has been found to predict which patients will benefit from adjuvant chemotherapy after surgery to remove the ovarian tumour and is used routinely in some centres to aid in decision-making.

Stroma ratio refers to the tumour: stroma ratio. A lower proportion of tumour cells or, conversely, a higher percentage of stroma, in a cancer tends to be associated with a poorer prognosis. This ratio has been found to be strongly associated with tumour growth and invasion in colorectal cancers, and to independently predict survival in patients undergoing surgery to removal colorectal tumours. However previous studies have looked mainly at more advanced colon cancers, rather than early rectal cancers, and have used only cancer-related death as the endpoint, rather than looking at local recurrence and response to adjuvant treatments.

Study Type

Observational

Enrollment (Actual)

150

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

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Participants diagnosed with rectal cancer that is operable and patients who have already had rectal cancer removed by transanal endoscopic microsurgery (TEM) in Oxford since 2007.

Description

Inclusion Criteria:

  • Participant is willing and able to give informed consent (in English) for participation in the study, or gave informed consent for donation of tissue for research at the time of surgery
  • Male or Female, aged 18 years or above
  • Diagnosed with operable rectal cancer
  • Due to undergo, or has already undergone, TEM surgery to remove rectal cancer
  • A useable tissue sample has already been, or will be, taken as part of routine surgery

Exclusion Criteria:

  • Age less than 18
  • Adults who are not able to give consent or who are deemed vulnerable
  • Participants who do not have a useable tissue sample will be excluded

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
Correlation Between Ploidy Status With Local Recurrence of Cancer
Time Frame: a minimum of 6 months after surgery
Results of ploidy status will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation with local recurrence of the rectal cancer
a minimum of 6 months after surgery
Correlation Between Tumour: Stroma Ratio With Local Recurrence of Cancer
Time Frame: a minimum of 6 months after surgery
Results of tumour:stromal ratio (TSR) will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation with local recurrence of the rectal cancer. A 50% cut-off is used to define high TSR.
a minimum of 6 months after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation Between Ploidy Status and Overall Survival After TEM Surgery to Remove Rectal Cancer
Time Frame: a minimum of 6 months after surgery
Results of ploidy status will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation between the test results and overall survival
a minimum of 6 months after surgery
Correlation Between Tumour:Stroma Ratio and Overall Survival After TEM Surgery to Remove Rectal Cancer
Time Frame: a minimum of 6 months after surgery
Results of tumour:stromal ratio (TSR) will be correlated with patient follow-up information for between 6 months and 9 years following surgery, to look for any correlation between the test results and overall survival. High TSR is defined using a 50% cut-off.
a minimum of 6 months after surgery

Collaborators and Investigators

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

Sponsor

Oxford University Hospitals NHS Trust

Collaborators

Oslo University Hospital

Investigators

  • Principal Investigator: Chris Cunningham, MD, Employee

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

March 29, 2017

Primary Completion (Actual)

May 31, 2019

Study Completion (Actual)

July 31, 2019

Study Registration Dates

First Submitted

January 30, 2017

First Submitted That Met QC Criteria

January 30, 2017

First Posted (Estimate)

February 1, 2017

Study Record Updates

Last Update Posted (Actual)

June 9, 2022

Last Update Submitted That Met QC Criteria

March 9, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 11846

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No individual data will be made available

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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