- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03039595
Ploidy and Stroma in Early Rectal Cancer
An Observational Study to Correlate the Results of Ploidy and Stroma Analysis With Prognosis in Early Rectal Cancer
Study Overview
Status
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
Enrollment (Actual)
Contacts and Locations
Study Locations
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Oxford, United Kingdom, OX3 7LE
- Churchill Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
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
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
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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
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a minimum of 6 months after surgery
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Correlation Between Tumour: Stroma Ratio With Local Recurrence of Cancer
Time Frame: a minimum of 6 months after surgery
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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.
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a minimum of 6 months after surgery
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Correlation Between Ploidy Status and Overall Survival After TEM Surgery to Remove Rectal Cancer
Time Frame: a minimum of 6 months after surgery
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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
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a minimum of 6 months after surgery
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Correlation Between Tumour:Stroma Ratio and Overall Survival After TEM Surgery to Remove Rectal Cancer
Time Frame: a minimum of 6 months after surgery
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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.
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a minimum of 6 months after surgery
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Chris Cunningham, MD, employee
Publications and helpful links
General Publications
- Bach SP, Hill J, Monson JR, Simson JN, Lane L, Merrie A, Warren B, Mortensen NJ; Association of Coloproctology of Great Britain and Ireland Transanal Endoscopic Microsurgery (TEM) Collaboration. A predictive model for local recurrence after transanal endoscopic microsurgery for rectal cancer. Br J Surg. 2009 Mar;96(3):280-90. doi: 10.1002/bjs.6456.
- Goh HS, Jass JR, Atkin WS, Cuzick J, Northover JM. Value of flow cytometric determination of ploidy as a guide to prognosis in operable rectal cancer: a multivariate analysis. Int J Colorectal Dis. 1987 Feb;2(1):17-21. doi: 10.1007/BF01648992.
- Kristensen GB, Kildal W, Abeler VM, Kaern J, Vergote I, Trope CG, Danielsen HE. Large-scale genomic instability predicts long-term outcome for women with invasive stage I ovarian cancer. Ann Oncol. 2003 Oct;14(10):1494-500. doi: 10.1093/annonc/mdg403.
- Park JH, Richards CH, McMillan DC, Horgan PG, Roxburgh CSD. The relationship between tumour stroma percentage, the tumour microenvironment and survival in patients with primary operable colorectal cancer. Ann Oncol. 2014 Mar;25(3):644-651. doi: 10.1093/annonc/mdt593. Epub 2014 Jan 23.
- Downey CL, Simpkins SA, White J, Holliday DL, Jones JL, Jordan LB, Kulka J, Pollock S, Rajan SS, Thygesen HH, Hanby AM, Speirs V. The prognostic significance of tumour-stroma ratio in oestrogen receptor-positive breast cancer. Br J Cancer. 2014 Apr 2;110(7):1744-7. doi: 10.1038/bjc.2014.69. Epub 2014 Feb 18.
- West NP, Dattani M, McShane P, Hutchins G, Grabsch J, Mueller W, Treanor D, Quirke P, Grabsch H. The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients. Br J Cancer. 2010 May 11;102(10):1519-23. doi: 10.1038/sj.bjc.6605674. Epub 2010 Apr 20.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
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)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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