gina.brown@rmh.nhs.uk

Colorectal GI Cancer Imaging Trials

Recruiting

Contact details if interested in joining trials:Professor Gina Brown

Gina.brown@rmh.nhs.uk

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Notes for NHS Costings• Interventional and non internventional trials: attract Local Network CRN funding per

patient recruited to enable support payment of clinical research nurses/ local trial coordination/research radiographer (the PI or Trust receives the funding to pay such costs)

• The interventional trials eg SERENADE, Beyond TME, MINSTREL and IMPRESS will attract greater funding £600-700 per patient and TRIGGER a higher amount as an IMP trial

• Any imaging including any workshop training for trials is funded in accordance with the NHS Accord agreement as treatment costs or excess treatment costs– no additional funding is required to participate.

• No separate applications for funding approval are required as all trials listed here are on the national CSP portfolio and all treatment plus excess treatment costs must automatically attract the necessary funding.

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MRI criteria and clinical trials• Tumours extending to or beyond TME plane –

Beyond TME and TRIGGER trials• EMVI positive tumours for preoperative CRT:

Serenade, Marvel and TRIGGER trial• T3c/T3d/T4 tumours for preoperative CRT:

TRIGGER trial• >2cm and <5cm endoscopic benign

polyp/suspected polyp cancer: MINSTREL trial• Tumours above 15cm or pelvic sigmoid: IMPRESS

trial

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MRI Trials and the Colorectal Patient Pathway

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• Rectal polyps should be excised with clear margins where possible

• Currently there is no recognised, relatively user independent, readily available imaging tool that can reliably asses depth of invasion

• Such an imaging tool may standardise management and assist clinicians in choosing the appropriate excision technique

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• Prospective diagnostic accuracy study open on the UK CRN portfolio.

• Sponsored by RMH and supported with a grant from the Pelican Foundation

• Target recruitment 55 patients across more than 5 sites over 18 months

• Test utility of MRI in identifying levels of invasion in benign and malignant rectal polyps 20mm to 50mm in size up to 150mm from anal verge.

• Novel study population using a novel staging tool that highlights boundaries relevant to clinical practice

• We recruit from endoscopy and all patients sent for an MRI scan. Unlikely to change treatment pathway for the vast majority of participants.

The Royal Marsden• Inclusion

20mm to 50mm polyp within 150mm of anal verge

• Exclusion

Polyp excised before MRI

Multiple polyps fulfilling the criteria

Polyp recurrence

Non adenoma or carcinoma

Declines study consent

Prisoners

Contraindication to MRI

• Withdrawal

No Histopathology available / DXT

Cannot tolerate MRI

Withdraws consent

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Beyond TMEThe role of MRI in improving outcomes and surgical

approaches for locally extensive primary or recurrent rectal cancer

• (An interventional trial for patients with confirmed primary locally advanced or recurrent rectal cancer beyond the TME plane

• The primary endpoint is to demonstrate that a histopathological complete resection with clear margin rate (R0) of >greater than 67% can be achieved using MRI compartmental classification planned exenterative surgery.

• Prospective validation of published MRI compartment staging system• Evaluation of pathway healthcare costs and quality of life and survival

outcomes for all patients with colorectal cancers that extend beyond the TME plane

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Beyond TMEInclusion Criteria:• Male or female, 18 years of age or older• Patients with confirmed primary locally advanced or recurrent rectal

cancer who require surgery beyond the TME planes (ie multivisceral resection, sacrectomy etc)

Data to be collected:MRI assessmentSurgeryHistopathologyQuaity of lifeSurvival outcomes

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IMPRESSImproving radical treatment through MRI

evaluation of pelvic sigmoid cancers

• Randomises patients with Sigmoid Cancer to either have a preoperative MRI or not. The aim of the trial is to measure the difference in proportion of patients undergoing radical treatment between the two arms, as well as mortality/morbidity and Quality of Life

• Hypothesis: accurate preoperative imaging will improve recurrence rate and survival rates through:

Better surgical decision making Selective preoperative therapy (eg Foxtrot trial, or preop CRT) in

high risk patients to downsize tumour

High risk featuresHigh risk features• Tumour involving non Tumour involving non

peritonealised fascial marginperitonealised fascial margin• Tumour penetration of adjacent Tumour penetration of adjacent

organsorgans• 4 or more involved nodes4 or more involved nodes• Extramural venous invasionExtramural venous invasion• Depth of extramural spread Depth of extramural spread

>5mm>5mm

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IMPRESSInclusion Criteria:• All patients with pelvic sigmoid colon

adenocarcinoma (demonstrated on colonoscopy and biopsy) who are eligible for curative treatment.

• Patients can be selected at colonoscopy if the tumour is above 15cm or on CT if tumour is above 15cm from the anal verge and below the iliac crest.

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IMPRESS Flow Chart

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SERENADEScreening for synchronous metastases in colorectal cancer using Hepatic Diffusion

weighted MRI• Study aims to see whether a short pre-operative Diffusion

Weighted MRI of the liver finds more liver metastases than standard CT alone.

• Eligible patients have high risk colorectal cancer and a CT which is negative or does not confirm the presence of metastatic disease. The trial is not randomised – everyone who is in the trial gets the liver DW-MRI. Patients with rectal cancer who are having radiotherapy get the DWMRI as part of their post CRT MR Scan.

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SERENADE

Inclusion Criteria:• Patient aged over 18 years• High risk primary colorectal cancer as determined

by pre-operative staging (MRI/CT)• CT negative or no confirmatory evidence of

metastatic disease

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SERENADE Flow Charts

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TRIGGERMagnetic Resonance Tumour Regression Grade

(mrTRG) As A Novel Biomarker To Stratify Management Of Good And Poor Responders To

Chemoradiotherapy: A Rectal Cancer Multicentre Randomised Control Trial

• Current recommendations are not to use the post-treatment MRI for decision-making but to plan treatment using the baseline (pre-treatment) MRI

• TRIGGER uses the post-treatment MRI to stratify treatment

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TRIGGER• Recently an MRI based tumour regression grade

(mrTRG) has been shown to stratify between tumours that respond well and those that respond poorly to CRT.

• ‘Good responders’ (mrTRG1&2) appear to have an excellent prognosis and it may be possible to avoid surgery altogether in this group. ‘Poor responders’ (mrTRG3-5) are at high risk of a poor oncological outcomes and additional therapy before surgery may improve their prognosis.

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TRIGGER Flow Chart

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TRIGGER

• For sites wishing to run a ‘deferral of surgery’ protocol for patients with a complete response following CRT, the TRIGGER trial will provide the necessary radiological training and trial support to make this possible

• Currently in the process of being approved, we are seeking expressions of interest from sites, interested in taking part in the TRIGGER feasibility study so please get in touch

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Summary• All trials on the UKCRN Portfolio• All multi-centre • If you wish to join please contact: Lisa Scerri, Senior Trial Coordinator

lisa.scerri@rmh.nhs.uk and she will guide you through the next steps.