21st century clinical trials a multidisciplinary approach

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21st century clinical trials - a
multidisciplinary approach

• Phil Quirke
• Pathology and tumour biology
• Leeds institute of Molecular Medicine

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Contributors

• Leeds Pathology Team Dr Fraser Lewis, Martin
  Waterhouse
• Oxford Sir Mike Brady and Prof David Gavaghan
• Marsden Dr Gina Brown
• Data team Prof Forman, Dr Eva Morris , Dr Brian
  Cottier
• Mercury,Core,Clasicc,Quasar,Focus, Aristotle,
  MAPE,Foxtrot,SCOT trial groups

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Contents

• Vision
• Background rectal cancer
• Current platform
• Possible future platform

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• Digital spectrum for trials
• Patient ---- radiology ---- pathology---- biology

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Why digital radiology pathology?

• Access original material
• Review
• Reclassification
• Quality assurance
• Further questions
• Link to clinical and biological information
• New freedoms
• Performed anywhere at any time
• Immediate access to data at the touch of a mouse

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Background

• Colorectal cancer management is multidisciplinary
• Management dependant on radiology/pathology
• Currently collect proforma clinical data but
  unable to centrally review/QA/study pathology and
  radiology
• Unable to add value from other databases

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NCRI Mercury study BMJ on line

• 354 of the 408 patients had a clear
  circumferential resection margin (87, 95
  confidence interval 83 to 90).
• Specificity for prediction of a clear margin by
  magnetic resonance imaging was 92 (327/354, 90
  to 95).

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MRC CR07 Quality of surgery-3 year LR rates (NCRI
ASCO plenary sessions 2006)
Local recurrence is reduced by good surgery and
further reduced by 5x5 radiotherapy
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Current systems and data

• Leeds - www.virtualpathology.leeds.ac.uk
• 5 Aperio scanners
• 15 terrabyte server
• High resolution digital slides mag x200-800
• MRI digital files
• Macroscopic digital/scanned photographs
• Oxford E-Diamond

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Current platform
Pathology Macroscopic photographs Histology
slides Special stains Tissue microarrays
Leeds
Mercury Clasicc Core Quasar Focus
Radiology MRI images Pre therapy Post therapy
Analysis
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HOME PAGE
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MRC CLASICC
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CORE STUDY
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Next platform
Other sites
Leeds

Mercury Clasicc Core Quasar Focus
Pathology Macroscopic photographs Histology
slides Special stains Tissue microarrays
Oxford

E- Diamond

Radiology MRI images Pre therapy Post therapy
Mercury Core

Marsden
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Next generation of colorectal trials

• Aristotle - chemoradiotherapy
• MAPE - low rectal cancer
• Foxtrot- chemotherapy in colon
• Enrol - early mobilisation
• SCOT - 3 vs 6 months therapy

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New linkages for added value

• Available in Leeds but unlinked
• Cancer Registries colorectal cancer data
• Colorectal cancer Health Episode Statistics
• Chemotherapy episode statistics
• Radiotherapy episode statistics
• Can we get added value to trials from data from
  other sources
• Automatic follow up and resource usage

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Future platform
Other sites
National data Via NHS number/D.O.B Colorectal
cancer registry data/link Secondary users spine
link Health episode statistics data/link Chemother
apy episode statistics/link Radiotherapy episode
statistics/link
Leeds


Aristotle MAPE Foxtrot Enrol SCOT
Oxford

Macroscopic photographs Histology slides Special
stains Pathology report Tissue microarrays
E- Diamond


Aristotle MAPE Foxtrot
MRI images Pre therapy Post therapy Recurrence Rad
iology report

Marsden
Informatics hub
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Summary

• Informatics platforms are essential for 21st
  century trials
• Add value
• Help answer important questions in colorectal
  cancer
• The UK can build a unique facility
• Can be delivered now with investment

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Thanks to

• Funders
• Department of Health
• NCRI, Wellcome, MRC CRUK
• CRUK

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New questions

• Aristotle
• Comparison of chemoradiotheray regimens in
  advanced rectal cancer
• Accuracy of prediction of post chemoradiotherapy
  complete surgical resection by MRI
• Is circumferential margin status an immediate
  predictor of disease free survival
• How good is surgery and what is the impact of
  poor quality of surgery post chemoradiotherapy
• Importance of pathology regression grading and
  its MRI prediction post chemoradiotherapy
• Real vs potential surgical planes

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New questions

• Foxtrot
• Chemotherapy vs no chemotherapy pre-surgery for
  colon cancer
• Accuracy of MRI staging of the colon
• Accuracy of prediction of downstaging of MRI
• Value of regression grading
• Does the quality of surgery matter in colon
  cancer?
• ENROL
• Enhanced recovery in open vs laparoscopic surgery
• Quality of laparoscopic surgery vs open

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New questions

• MAPE
• Investigating primary perineal approach to low
  rectal cancer
• Radiology/pathology correlations and questions
• SCOT
• 6 months vs 3 months treatment adjuvant therapy
• Identification of low/high risk Bs
• Tissue microarrays for profiling