Gina Brown Pent Mon
Gina Brown Pent Mon
Gina Brown Pent Mon
gina.brown@rmh.nhs.uk
Advances in Imaging
Technology
Rectal Cancer
Professor Gina Brown
Royal Marsden Hospital
Imperial College
UK gina.brown@rmh.nhs.uk
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Quantitative Biomarkers in
Imaging
• Predicting prognosis – stage assessment
• Predicting response
• Assessing response
• Independent prognostic / predictive
imaging biomarkers to determine
treatment
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conc
SI/ Gd
Muscle
Permeability
Perfusion
Diffusion
Pre-treatment tumour
Permeability, Perfusion and
Diffusion predict response to George M, Dzik-Jurasz ASK et al, BJS 2001
Dzik-Jurasz ASK et al, Lancet 2002
chemoradiotherapy
“the mean is significantly higher
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for responders….”
What does data such as
this this mean for an
individual patient?
How can this be
translated to clinical
practice?
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“We used the ad-hoc analysis because when starting the study no earlier
data was available to set the cutoff value.”
Before clinical implementation of the DCE-MR for response assessment
a larger prospective multicenter study with a predefined cutoff value will
need to be performed…..
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Janssen et al
Int J Radio. Biol. Phys
2011
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Metabolic response
Post Radiotherapy
Acute inflammatory
changes
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of new technologies?
Method Prospectively validated against DFS
outcomes
MRI DWI No – many retrospective quantitative cut-offs and
qualitative assessments – none prospectively
validated
Checklist of Biomarker
Recommendations
1. Has the proposal laid out proof of a
clinical need i.e. proof of
outcomes/consequence.
2. What is the true degree of
error/deficiency and consequence in
current non-quantitative imaging or non
imaging test ?
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Checklist of Biomarker
Recommendations
3. Does the biomarker being tested have a
predefined threshold/criteria or range for
positive vs negative test or is it exploratory –
if exploratory (ie shown a correlation)
4. Have the authors then completed the study
by defining and then validating thresholds in
an independent dataset
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Checklist of Biomarker
Recommendations
5. Has the biomarker been tested
against other clinical variables and
other imaging methods of
assessment and found to be an
independent predictor compared with
the current best standards of care?
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Checklist of Biomarker
Recommendations
6. Has the imaging measure been
tested against PFS/DFS/survival
outcomes and shown to be
independent of existing clinical and
imaging non quantitative tests?
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MERCURY trial
• 2002-2003
• 11 international centres (30 radiologists)
• 295 patients undergoing primary surgery
• Policy to avoid pre and post operative radiotherapy
for mrCRM clear, mrEMVI negative, T3b or less
rectal cancers, regardless of N stage
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“Shihab et al: MRI staging of low rectal cancer." Eur Radiol 19(3): 643-650.
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MRI 31
UK Royal College of
Pathologists Guidelines 2014
• pEMVI detection rates should be
>30%
• For units with <30%, should use
elastin staining
• MRI is reliable as method of detecting
EMVI and can be used to audit
pathology
• Lone arteriole sign, to improve
detection of discontinuous vascular
deposits
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Characteristic features of
mrEMVI• Expansion of
extramural vessels
by tumour
• Serpiginous /
tubular extension
of tumour signal
MRI for detection of extramural vascular invasion
in rectal cancer.
AJR Am J Roentgenol 191(5): 1517-1522.
mrEMVI is associated with pelvic
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BJS. 2008
71%
60
40 p = 0·0015
free
32%
20
0
0 1 2 3 4 5 6
Time since operation (Years)
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Assessing response
Method Prospectively validated against DFS
outcomes
MRI DWI No – many retrospective quantitative cut-offs and
qualitative assessments – none prospectively
validated
MR TRG
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(Patel et al JCO 2011)
MRI TRG 1-3
72% at 5 yrs
p=0.001
HR 3.28 (95%CI; 1.22–8.80).
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after Chemo-Radiotherapy
in EXPERT-C trial (both arms)
mrTRG1-2
89.8%
67.5%
65.9%
mrTRG1-2, 39.8%
mrTRG3 , 29%
mrTRG4-5, 31%
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mrTRG is a prognostic
(and predictive) biomarker
– Shows good interobserver radiology agreement and
reproducibility
– MERCURY trial (JCO 2011 – multiple radiologists)
– EXPERT-C trial
– GEMCAD study (17 radiologists)
– CORE study (interobserver agreement)
– Identified 40% of patients with mrTRG1/2 – 89.8% overall
survival. Compared with only 8.8% patients with pathologic CR.
– Therefore mrTRG could be justified as a more clinically relevant
endpoint
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mrTRG is a prognostic
(and predictive) biomarker
• Shows good interobserver radiology agreement and reproducibility
● MERCURY trial (JCO 2011 – multiple radiologists)
● EXPERT-C trial
● GEMCAD study (17 radiologists)
● CORE study (interobserver agreement)
● MERCURY 2 trial – risk factor for CRM involvement
• In EXPERT C trial identified 40% of patients with mrTRG1/2 – 89.8% overall
survival. Compared with only 15% pathologic CR rate (90% survival).
• Therefore mrTRG could be justified as a more clinically relevant endpoint
TRIGGER :
randomised
phase III trial
patients will be
randomised to
an mrTRG based
treatment
strategy
Training of
Radiologists to
undertake
mrTRG
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www.slideshare.net/ginabrown3
• MRI reporting templates
• MRI high resolution technique
• How to identify mrEMVI
• Details of workshops for surgeons
and radiologists
Reporting Minimum Standards
Baseline assessment of Rectal cancer MRI report
Primary tumour Lymph node assessment
The primary tumour is demonstrated as an [ Annular | Semi-annular | Ulcerating | | Polypoidal | Only benign reactive and no suspicious nodes shown [N0]
Mucinous] mass with a [nodular / smooth] infiltrating border. [ ] mixed signal/irregular border nodes [N1/N2]
Extramural venous invasion: [ No evidence ] [ Evidence]
The distal edge of the luminal tumour arises at a height of [ ] mm from anal verge: [ ] Small [ ]Medium [ ]Large vein invasion is present
The distal edge of the tumour lies [ ]mm [Above,at, below] the top of the puborectalis sling CRM
The tumour extends craniocaudally over a distance of [ ] mm The closest circumferential resection margin is at o’clock
The proximal edge of tumour lies [above at below] the peritoneal reflection The closest CRM is from [Direct spread of tumour] [Extramural venous invasion] [Tumour
deposit]
Invading edge of tumour extends from [ to ] O’clock
Minimum tumour distance to mesorectal fascia: mm [CRM clear ] [CRM involved]
Tumour is [confined to] [extends through] the muscularis propria:
Peritoneal deposits: [ No evidence] [ Evidence]
Extramural spread is [ ] mm Pelvic side wall lymph nodes:
mrT stage: [T1 ] [ T2 ] [ T3a] [ T3b ] [ T3c] [ T3d ] [T4visceral ] [T4 [ None] [ Benign] [ Malignant mixed signal/irreg border]
peritoneal] Location: [Obturator fossa • R •L ] . [External Iliac Nodes • R •L] .[ Internal iliac • R •L ]
Tumour is [present] [not present] the level of the puborectalis sling at this level: Summary: MRI Overall stage: T N M [CRM clear] , [ CRM involved ] , [ EMVI
[Tumour is confined to the submucosal layer/part thickness of muscularis propria indicating that the positive] [EMVI negative],[PSW positive ] [PSW negative]
intersphincteric plane/mesorectal plane is safe and intersphincteric APE or ultra low TME is No adverse features eligible for primary surgery
possible] High risk safe margins for preoperative therapy : eligible for Serenade, Marvel
[Tumour extends through the full thickness of the muscularis propria : intersphincteric Poor prognosis unsafe margins eligible for preoperative chemoradiotherapy: eligible for 6 vs 12
plane/mesorectal plane is unsafe, Extralevator APE. is indicated for radial clearance] trial
[Tumour extends into the intersphincteric plane : intersphincteric plane/mesorectal plane is unsafe, Low Rectal <6cm – eligible for the Low Rectal Study.
therefore an extralevator APE. is indicated for radial clearance]
[Tumour extends into the external sphincter : intersphincteric plane/mesorectal plane is unsafe.]
[ Tumour extends into adjacent [prostate/vagina/bladder/sacrum] : exenterative procedure will be
required
Additional comments:
.
Reporting Template Post Treatment
Post Treatment Assessment MRI Rectal Cancer Lymph nodes:
Comparison is made with the previous examination of: • None /Only benign reactive [N0]
• The treated tumour: shows no fibrosis,TRG5 • Present number mixed signal/irregular border [N1/N2]
• Less than <25% fibrosis, predominant tumour signal, TRG4
• 50% tumour/fibrosis, TRG 3 Extramural venous invasion: [• No evidence • Evidence]
•>75% fibrosis, minimal tumour signal intensity,TRG2 [• Small • Medium • Large]
•low signal fibrosis only no intermediate tumour signal TRG1 CRM
Closest circumferential resection margin: [ ]O’clock
The distal edge of the luminal tumour arises at a height of [ ] mm from anal verge: Closest CRM is from [ Direct spread of tumour • Extramural venous invasion • Tumour deposit]
The distal edge of the tumour lies [ ]mm [Above, at, below] the top of the puborectalis sling Minimum tumour distance to mesorectal fascia: [ ]mm [ • CRM clear • CRM involved]
compared with []mm previously
The tumour extends craniocaudally over a distance of [ ] mm compared with [ ]mm previously Peritoneal deposits: [• No evidence • Evidence ]
The proximal edge of tumour lies [above at below] the peritoneal reflection
The invading edge of treated tumour extends from [ to ] O’clock Pelvic side wall lymph nodes: • None • Benign • Malignant
Tumour signal is [Confined to / Extends through the muscularis propria.] [Location: Obturator fossa • R •L . External Iliac Nodes •R •L. Inf Hypogastric •R •L ]
Fibrotic signal is [ Confined to / Extends through muscularis propria.]
Extramural spread: [ ]mm for tumour signal [ ]for fibrotic stroma Summary: y MRI Overall stage ymrT ymr N M , TRG
• Low/intermediate risk, CRM clear, TRG 1-2, EMVI negative
yMR T stage: • T1 • T2 • T3a • T3b • T3c • T3d •T4 visceral •T4 peritoneal • High prognosis, CRM pos or TRG4/5 or EMVI positive
Treated tumour [is/ is not] present at or below the puborectalis sling TRG1-2 low tumour – eligible for consideration for deferral of surgery
• tumour signal/fibrosis extends into the submucosal layer/part thickness of muscularis propria :
intersphincteric plane/mesorectal plane is safe intersphincteric APE or ultra low TME possible, CRM
is safe
• tumour signal/fibrosis extends through the full thickness of muscularis propria : intersphincteric
plane/mesorectal plane is unsafe, for extralevator APE.
• tumour signal/fibrosis extends into external sphincter : intersphincteric plane/mesorectal plane is
unsafe:for extralevator APE
•tumour signal/fibrosis extends into beyond external sphincter into [prostate/vagina ] : intersphincteric
plane / mesorectal plane is unsafe, for extralevator APE.