MRI for identifying the high risk rectal cancer

Gina BrownRoyal Marsden and Imperial

College, London, UKGina.Brown@rmh.nhs.uk

Teaching Resources: www.slideshare.net/ ginabrown3

No disclosures

Colorectal MRI Specialist Radiologist

can help improve surgical outcomes

By identifying the high risk rectal cancer

#1. Identifying patients at risk of Local Recurrence

First description of the mesorectal fascia using MRI. Brown G, Radiology 1999

Hazard ratio3.8 (95%CI: 1.7 -8.5)

#2. Identifying patients who require surgery beyond TME

C. Post anterior exenteration appearance

3. Anatomic Surgical and Therapeutic Road Map

#3. Identifying mucinous tumours

MRI more accurate compared with initial biopsy in diagnosing mucinous cancers

• In patients with locally advanced rectal cancer, the proportion of mucinous tumours diagnosed on MRI was 18%, compared with only 5% on initial biopsy.

• All 60 patients undergoing surgery for mrMucinous tumours were confirmed as such on final histopathology.

• The diagnostic odds for detection of mucinous subtype on preoperative MRI compared histopathological biopsy assessment = 4.67 (95% CI: 2.61–8.35).

Three year DFS for patients for mrMucinous tumours was significantly worse than mrNon-mucinous tumours: 48% (95% confidence interval = 33–62%) versus 71% (95% confidence interval = 65–77%) respectively, p = 0.006

23 DFS events18/23 (78%) developedmetastatic disease 5/23 (22%) developed localrecurrence.

Significantly less likely to achieve T downstaging, and N downstaging Almost four fold higher risk of CRM involvement

Lack of downstaging in a mucinous tumour deposit

Before treatment After treatment

4. Staging and assessment of low rectal cancer

Battersby, N. J., How, P., Moran, B., Stelzner, S., West, N. P., Branagan, G. et al. MERCURY II Study Group. (2015). Prospective Validation of a Low Rectal Cancer Magnetic Resonance Imaging Staging System and Development of a Local Recurrence Risk Stratification Model: The MERCURY II Study. Ann Surg. 2015

#4. Staging and assessment of low rectal cancer

Low Rectal Carcinoma: The T staging is less relevant than the fact that less than

1mm of muscularis is preserved at invasive border of the tumour at the top of the

sphincter complex, the TME plane CRM is at risk

MRI prediction of outcome for low rectal cancer

Salerno et al, Diseases Of The Colon & Rectum Volume 52: 4 (2009)

Tumour classification for low rectal cancers

1. MRI Low Rectal Stage 1: tumour on MRI images appears confined to bowel wall butnot through full thickness (intact muscularis propria of the internal sphincter).

2. MRI Low Rectal Stage 2: tumour on MRI replaces the muscle coat of the internalsphincter but does not extend into the intersphincteric plane. Above the level of thesphincter it is confined to the mesorectum.

3. MRI Low Rectal Stage 3: tumour on MRI invading into the intersphincteric plane orlying within 1mm of levator muscle above the level of the sphincter complex.

4. MRI Low Rectal Stage 4: tumour invading into the external anal sphincter andinfiltrating/ extending beyond the levators +/- invading adjacent organ. Above thesphincter tumour invades the levator muscles.

Endpoints:• Reduction in CRM positive rate from 30% to <15%• Sample Size

Reduce pCRM involvement from to <15% 90% power, 20% drop out – 271 patients

• Validate MRI based staging system for low rectal cancers in predicting the plane of surgery

• Map the preoperatively defined planes –surgical outcomes

MERCURY II: low rectal studyAshford St Peters Hospital, EnglandEpsom & St Helier, EnglandFrimley Park Hospital, EnglandMayday University Hospital, EnglandSalisbury Hospital, EnglandRoyal Marsden Hospital, EnglandDresden, GermanyKrankenhaus Friedrichshain, GermanyNorth Hampshire Hospital, EnglandAarhus DenmarkBelgradeEast Surrey

BirminghamChichesterPoole

Results: pCRM Involvement MERCURY I v MERCURY II

Results

• Analysis of 158 Mercury I patients and 288 Mercury II patients

• All cause pCRM involvement in low rectal cancers from Mercury I v compared with MERCURY II20% to 8.7% (95% CI 5.5 – 12.0, p=0.001)

Due to implementation of staging system – selective use of preoperative therapy and ELAPE surgery for MRI defined high risk patients

MRI predictors of pCRM involvement Univariable Analysis Multivariable Analysis

Odd ratio (95% CI) p value Odd ratio (95% CI) p value

All Cause pCRM in all patients (Surgery with or without neoadjuvant therapy, n=288) All cause mrLRP

‘Safe’ ‘Unsafe’

1 5.3 (2.2 – 12.8)

0.001

1 3.5 (1.3 – 8.9)

0.011

MRI distal TME plane ‘Safe’ (mrLR 1&2) ‘Unsafe’ (mrLR 3&4)

1 5.6 (2.4 – 13.4)

0.001

MRI Mesorectal Fascia TME ‘Safe’ ‘Unsafe’

1 4.8 (1.9 – 11.6)

0.001

Tumour Site Other Anterior

1 2.8 (1.0* – 5.2) 0.052

1 2.57 (1.1-6.2) 0.037

MR Height (from the anal verge)

≥ 4cm < 4cm

1 3.2 (1.4-7.5) 0.008

1 2.5 (1.0-6.3) 0.047

mrT stage ≤mrT3b >mrT3b

1 4.4 (1.9 – 10.2)

0.001

MR Node Negative Positive

1 4.4 (1.2 – 17.6)

0.033

MR EMVI Negative Positive

1 4.5 (1.9 – 10.4)

0.001

1 3.3 (1.3 – 8.3)

0.012

53%MRIHeight <4cm 26 31

25

31

12%

5%

4%

9%

4%

12%

5%

15%

No Risk Factors2% pCRM risk

MRI Tool for predicting risk of pCRM involvement

mr ‘Unsafe’ plane

mrEMVI

MRI invading edgeAnterior

#5. MRI assessment of depth of tumour spread gives the most accurate prognostic information#5. MRI assessment of depth of tumour spread

gives the most accurate prognostic information

Measuring depth of extramural spread (Radiology 2007)

295/311 (95 %) patients who underwent primary surgery. The mean difference between MRI and histopathology assessment of tumor EMD was -0.046 mm, SD = 3.85 mm, the 95 % CI was -0.487 to 0.395 mm. MRI and histopathology assessment of tumor spread are considered equivalent to within 0.5 mm (R). Radiology 2007

T2 or T3 tumour without adverse features

MERKEL et al 2001

pT3<5mm, N any

•T2 and T3 tumours <5mm have 85-90% 5 year cancer specific survivalMerkel et al(2001).Int J Colorectal Dis 16(5): 298-304.

Outcomes for MRI good prognosis rectal cancers

Taylor et al, MERCURYAnnals of Surgery 2011

#6 An opportunity to identify Early Rectal Lesions suitable for local excision approach

#6 An opportunity to prevent incorrect removal by local

excision approach

A good prognosis tumour?Looks like a T1sm3

Discontinuous EMVI in low rectal cancer

Discontinuous EMVI in ERCAnd a pelvic sidewall deposit

#7 MRI identification of EMVI

#8.Lateral Pelvic Tumour Spread

#9 Reassessing after chemoradiotherapy - mrTRG

#10 Surveillance

The Royal Marsden

TRIGGER trial

Objectives of trial

• recruit patients and stratify treatment using mrTRG directed management. The ‘good responders’ (mrTRG1&2) often have no evidence of tumour and it may be possible to avoid surgery in this group (deferral of surgery).

• The ‘poor responders’ (mrTRG3-5) are at high risk of poor oncological outcomes and additional therapy before surgery may improve prognosis.

Phase III• the phase III trial will be designed to detect an

improvement in 3 year DFS in the intention to treat population from 74% to 82% (i.e. a hazard ratio of 0.66) with 80% power and a 5% 2- sided level of statistical significance.

• 633 patients over 3-5 years – recruitment rate 5-11 patients (total from all sites) randomised per month

Radiology support and training• To ensure consistency, a nominated study GI

radiologist will be asked to participate in an CME-accredited trial-specific MRI reporting workshop/webinar.

• A site will not be able to open until the allocated radiologist has achieved mrTRG competency (mrTRG kappa ≥ 0.7). But training and support will be available to enable all radiologists to achieve this.

Feasibility secondary endpoints• Assess response rates by comparing the reported

mrTRG in the control and intervention arm• Evaluate the reproducibility of mrTRG by recruiting

radiologists• To evaluate safety by assessing acute drug toxicity and

30 day surgical morbidity• pCRM involvement rate in the control versus intervention

arm• Quality of surgery in control vs intervention arms

restaging MRI – prognostic/predictive imaging biomarkers for DFS

• mrTRG 1-2 has similar DFS and OS as pCR but seen 4 times more frequently than pCR (prospective randomised trial data) – expecting 30-40% of all enrolled to defer surgery

• mrTRG1-2 represents a population of patients highly likely to have no viable tumour hence suitable for MRI monitoring in deferral of surgery trial

What resources needed to implement this

• Dedicated MDT radiologists 2 per colorectal surgical team – gain volume/experience

• Workshop training >1000 radiologists trained by this method, training 1 radiologist costs less than the price of 1 MRI scan

• Synoptic reporting• MDT administrators to ensure cases are available to be read by

Radiologist prior to MDT meeting• Participation in clinical trials – mandates good practice

MRI Trials and the Colorectal Patient Pathway

protocols from gina.brown@rmh.nhs.uk

RECTAL MRI INTENSIVE TWO DAY WORKSHOP

WITH HANDS ON WORKSTATION PRACTICE FOR RADIOLOGISTS, SURGEONS AND ONCOLOGISTS

Euston House

24 Eversholt Street London NW1 1AD

Aims: This course enable will equip you to ensure high quality MRI in your institution and to be able to evaluate baseline and post treatment MRI assessment of rectal cancer and pelvic anatomy with confidence for your daily practice.

Day One Will provide you with essential knowledge for MDT working and MRI assessment in different clinical scenarios with details revision of anatomy and interpretation criteria as a preparation for Day Two.

Day Two Will give you hands on workstation practice for assessing rectal cancer cases and pelvic anatomy and how this is applied to treatment planning. For teams participating in MINSTREL, TRIGGER AND STARTREC trials, you will be certified as having sufficient training to take delegated responsibility for trial participation.

PROFESSOR GINA BROWN

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Course Code M00117 30th 31st January 2017 Full 2 day course, 30th 31st January £550 early bird

Booking after 29th December: £650 Day One only, 30th January £300 Day Two only, 31st January £350

Course Code M0317 30th 31st March 2017

Full 2 day course, 30th 31st March £550 early bird Booking after 28th February: £650

Day One only, 30th March £300 Day Two only, 31st March £350

Course Code M0617 8th 9th June 2017

Full 2 day course, 8th 9th June £550 early bird Booking after 7th May: £650

Day One only, 8th June £300 Day Two only, 9th June £350

Course Code M0917 28th 29th September 2017

Full 2 day course, 28th 29th September £550 early bird Booking after 27th August: £650

Day One only, 28th September £300 Day Two only, 29th September £350

Please return registration form to Gina.Brown@rmh.nhs.uk or Fax: + 44 (0) 20 8915 6721 You will receive confirmation of your registration within 2 working days together with an invoice and instructions for payment. Without written confirmation your booking is not valid, without payment your place is not guaranteed.

Please contact +44 (0) 20 8661 3964 if you have any queries

REVISE TIPS AND TRICKS FOR:

Pelvic applied anatomy assessment skills

MDT based working

MRI rectal cancer interpretation skills

Case discussions and controversies

Rectal cancer scanning standards

Hands on workstation cases with live feedback and

course booklet

Registration

Two day workshop combined cost (early bird)) £550 Day One only MDT working and revising the MRI interpretation £300

Day Two only Workstation practice, self-testing with answer booklet and notes £350 Price includes lunch and refreshments for each delegate on both days. Capacity is limited so to guarantee your place, please complete the registration section of this flyer and return as soon as possible

11 CPD points applied for