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Rectal Diseases

Neoplasms, Cystic, Mucinous, and Serous

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Colonic Diseases

Patients with mrEMVI positive rectal cancer

Patients with mrEMVI negative rectal cancer

Gina Brown

Extramural venous invasion (EMVI) is the spread of microscopic tumour cells into the veins around the tumour. Rectal cancer treatment has improved greatly over recent years. However, it is important for us to learn as much about the tumours as possible in order to develop newer therapies. Current treatments may benefit from new genetic information relating to the cancer. We hope to identify genetic differences in certain types of rectal cancer which will allow future treatments.

Neoadjuvant chemoradiotherapy (CRT) is widely accepted as beneficial to selected patients in terms of decreased risk of local recurrence and overall survival. Current management of rectal cancer involves risk stratification through pre-operative staging leading to formulation of treatment strategy. Very little is known about the long-term outcomes and response to CRT on MRI detected extramural venous invasion (mrEMVI). Although mrEMVI is accepted as a marker of poor prognosis, whether it has a predictive value and should be specifically treated is not known.

Molecular and genetic profiling provides us with an opportunity to understand the underlying mechanisms which govern clinical behaviour in rectal cancer. Using high-throughput technology such as tissue microarray analysis allows large-scale analysis of specimens in a relatively short amount of time. It offers the ability to compare the molecular profiles of different subtypes of rectal cancer such as mrEMVI-positive and -negative tumours and whether any changes are observed following CRT. This can then be correlated with clinical behaviour over the medium and long-term with regards to local recurrence, distant metastases and overall survival.

This study will identify important differences between key rectal cancer tumour subtypes. Identification of reliable pathological markers of EMVI pathways (from both the primary tumour sample, but more importantly from the pre-operative biopsies) has real potential for taking us a step closer to more personalised management of rectal cancer by establishing prognostic biomarkers reflective of disease type, but also through the underlying biology that may be highlighted (with its promise of therapeutic translation).

Histopathology samples taken after rectal tumour removal surgery will be analysed using micrarray techniques. The pathological tissue microarrays (TMAs) will be generated using the Alphelys Tissue Arrayer Minicore®3 system. Markers that will be evaluated will be initially directed at epithelial to mesenchymal (EMT) transition pathways, as our preliminary studies suggest that this phylogenetically conserved molecular program has important roles in tumour dissemination and resistance to conventional chemotherapy.

Molecular, Pathologic and MRI Investigation of the Prognostic and Redictive Importance of Extramural Venous Invasion in Rectal Cancer (MARVEL) Trial

Molecular, Pathologic and MRI Investigation of the Prognostic and Redictive Importance of Extramural Venous Invasion in Rectal Cancer

mrEMVI Regression Grade Scoring Table: Grade 5 - No response (intermediate signal intensity, same appearances as original tumour) Grade 4 - Slight response (little areas of fibrosis or mucin but mostly tumour) Grade 3 - Moderate response (\>50% fibrosis or mucin, and visible intermediate signal) Grade 2 - Good response (dense fibrosis; no obvious residual tumour, signifying minimal residual disease or no tumour) Grade 1 - Radiological complete response (rCR) (linear/crescentic 1-2mm scar in mucosa or submucosa only.)

Pelican Cancer Foundation

Royal Marsden NHS Foundation Trust

Patients will be registered whose rectal tumours are mrEMVI positive (i.e. EMVI is present in baseline and post-chemoradiotherapy MRI scans).

Patients registered who were mrEMVI positive at baseline MRI but have become mrEMVI negative post-chemoradiotherapy.

Two blood samples are taken from each patient with mrEMVI positive tumours post chemoradiotherapy. One pre-surgery and one during surgery from a peripheral vein.

Blood sample (mrEMVI positive patient)

Blood sample (mrEMVI negative patient)

Caroline Martin

Syvella Ellis

Sharon Turney

Jess Evans

Afeez Adebesin

James Kinross

Cordelia Grant

Christos Kontovounisios, MD

Gina Brown, MD

This study does not involve randomization or treatment. Eligible patients have colorectal adenocarcinoma with no metastases eligible for curative surgery. A pre operative staging scan must have been completed within 6 weeks prior to surgery. Two x 20ml blood samples will be taken from each patient, one prior to and one during or within 24hrs after surgery. Patients are annually followed up to 3 years.

A multicentre observational study, ctDNA aims to provide the evidence base for metatstatic disease being caused by vascular methods of spread by determining if there is a link between EMVI status and ctDNA

Each patient will have two blood samples taken that will be analysed for ctDNA. One blood sample will be taken at the time of preoperative assessment, after chemoradiotherapy, and a further sample will be taken intraoperatively, from the peripheral vein of the patient's arm. For each of the blood samples the presence or absence of ctDNA mutations (kras and p53) will be identified.

Circulating Tumour DNA (ctDNA) in Patients With Colorectal Cancer and the Relationship to Imaging Features of Extramural Venous Invasion

Proportion of patients who are EMVI positive demonstrating higher % mutation frequency of circulating cell-free and tumour specific DNA compared with patients who are EMVI negative.

Measure the intraoperative % mutation frequency of ctDNA in EMVI positive compared with EMVI negative patients

Record survival outcomes of patients who are: EMVI negative with low ctDNA levels, EMVI negative with high ctDNA levels, EMVI positive with low ctDNA levels, EMVI positive with high ctDNA levels

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Molecular, Pathologic and MRI Investigation of the Prognostic and Redictive Importance of Extramural Venous Invasion in Rectal Cancer (MARVEL) Trial	NCT01995942	Adenocarcinoma Rectal Diseases Colorectal Neop... Adenocarcinoma,... Carcinoma Neoplasms, Glan... Neoplasms by Hi... Neoplasms Neoplasms, Cyst... Intestinal Neop... Gastrointestina... Digestive Syste... Neoplasms by Si... Digestive Syste... Gastrointestina... Intestinal Dise...		18 Years -	Royal Marsden NHS Foundation Trust
Circulating Tumour DNA (ctDNA) in Patients With Colorectal Cancer and the Relationship to Imaging Features of Extramural Venous Invasion	NCT02579278	Cancer Rectal Cancer	Blood sample (m... Blood sample (m...	16 Years -	Imperial College London

Spots Global Cancer Trial Database for emvi

Every month we try and update this database with for emvi cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for emvi

Every month we try and update this database with for emvi cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for emvi cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.