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MRI for identifying the high risk rectal cancer


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Identifying which patients should receive preoperative chemo-radiotherapy. MRI staging of prognostic factors in rectal cancer and prevention of local and distant recurrence in high risk patients.

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MRI for identifying the high risk rectal cancer

  1. 1. MRI for identifying the high risk rectal cancer Gina Brown Royal Marsden and Imperial College, London, UK Teaching Resources: ginabrown3
  2. 2. No disclosures
  3. 3. Colorectal MRI Specialist Radiologist can help improve surgical outcomes By identifying the high risk rectal cancer
  4. 4. #1. Identifying patients at risk of Local Recurrence First description of the mesorectal fascia using MRI. Brown G, Radiology 1999 Hazard ratio 3.8 (95%CI: 1.7 -8.5)
  5. 5. #2. Identifying patients who require surgery beyond TME C. Post anterior exenteration appearance
  6. 6. 3. Anatomic Surgical and Therapeutic Road Map #3. Identifying mucinous tumours
  7. 7. 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).
  8. 8. 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 events 18/23 (78%) developed metastatic disease 5/23 (22%) developed local recurrence.
  9. 9. Significantly less likely to achieve T downstaging, and N downstaging Almost four fold higher risk of CRM involvement
  10. 10. Lack of downstaging in a mucinous tumour deposit Before treatment After treatment
  11. 11. 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
  12. 12. 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
  13. 13. MRI prediction of outcome for low rectal cancer Salerno et al, Diseases Of The Colon & Rectum Volume 52: 4 (2009)
  14. 14. Tumour classification for low rectal cancers 1. MRI Low Rectal Stage 1: tumour on MRI images appears confined to bowel wall but not 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 internal sphincter but does not extend into the intersphincteric plane. Above the level of the sphincter it is confined to the mesorectum. 3. MRI Low Rectal Stage 3: tumour on MRI invading into the intersphincteric plane or lying 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 and infiltrating/ extending beyond the levators +/- invading adjacent organ. Above the sphincter tumour invades the levator muscles.
  15. 15. 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
  16. 16. MERCURY II: low rectal study Ashford St Peters Hospital, England Epsom & St Helier, England Frimley Park Hospital, England Mayday University Hospital, England Salisbury Hospital, England Royal Marsden Hospital, England Dresden, Germany Krankenhaus Friedrichshain, Germany North Hampshire Hospital, England Aarhus Denmark Belgrade East Surrey Birmingham Chichester Poole
  17. 17. 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 II 20% 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
  18. 18. 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
  19. 19. 53% MRI Height <4cm 26 31 25 31 12% 5% 4% 9% 4% 12% 5% 15% No Risk Factors 2% pCRM risk MRI Tool for predicting risk of pCRM involvement mr ‘Unsafe’ plane mrEMVI MRI invading edge Anterior
  20. 20. #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
  21. 21. 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
  22. 22. T2 or T3 tumour without adverse features
  23. 23. pT3<5mm, N any •T2 and T3 tumours <5mm have 85-90% 5 year cancer specific survival Merkel et al(2001).Int J Colorectal Dis 16(5): 298-304.
  24. 24. Outcomes for MRI good prognosis rectal cancers Taylor et al, MERCURY Annals of Surgery 2011
  25. 25. #6 An opportunity to identify Early Rectal Lesions suitable for local excision approach #6 An opportunity to prevent incorrect removal by local excision approach
  26. 26. A good prognosis tumour? Looks like a T1sm3
  27. 27. Discontinuous EMVI in low rectal cancer
  28. 28. Discontinuous EMVI in ERC And a pelvic sidewall deposit
  29. 29. #7 MRI identification of EMVI
  30. 30. #8.Lateral Pelvic Tumour Spread
  31. 31. #9 Reassessing after chemoradiotherapy - mrTRG
  32. 32. #10 Surveillance
  33. 33. The Royal Marsden TRIGGER trial
  34. 34. 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.
  35. 35. 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
  36. 36. 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.
  37. 37. 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
  38. 38. 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
  39. 39. 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
  40. 40. MRI Trials and the Colorectal Patient Pathway protocols from
  41. 41. 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 Registration Form Name: Position: Institution: The information above will appear on your badge for the course email: Tel: Address: I wish to register for (please tick as appropriate): Course Code M00117 30 th 31 st January 2017 Full 2 day course, 30 th 31 st January £550 early bird Booking after 29 th December: £650 Day One only, 30 th January £300 Day Two only, 31 st January £350 Course Code M0317 30 th 31 st March 2017 Full 2 day course, 30 th 31 st March £550 early bird Booking after 28 th February: £650 Day One only, 30 th March £300 Day Two only, 31 st March £350 Course Code M0617 8 th 9 th June 2017 Full 2 day course, 8 th 9 th June £550 early bird Booking after 7 th May: £650 Day One only, 8 th June £300 Day Two only, 9 th June £350 Course Code M0917 28 th 29 th September 2017 Full 2 day course, 28 th 29th September £550 early bird Booking after 27 th August: £650 Day One only, 28 th September £300 Day Two only, 29 th September £350 Please return registration form to 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