The advent of digital microscopy Yves Sucaet, Wim Waelput, Peter In’t Veld Biology edition
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The advent of digital
microscopy
Yves Sucaet, Wim Waelput,
Peter In’t Veld
Biology edition
02-05-2023 pag. 2
Financial disclosure
• Yves Sucaet and Wim Waelput are co-founders and shareholders in Pathomation, an innovative company founded in 2012. The company strives to offer the most comprehensive software platform for digital pathology possible. The focus is on integration, scalability, and user-friendliness. Pathomation implements digital pathology in a variety of use cases and scenarios.
02-05-2023 pag. 3
Prelude
• In October 2016, I was honored at Troy University as one of its 2016 “alumni of the year” during the annual homecoming activities.
• In the following week, I gave several guest lectures in various departments across campus.
• This is the lecture as presented for the biology department on Monday, October 17, 2016.
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Topics for today
• How did I get here?• Digital microscopy• Digital pathology• Companion diagnostics
PERSONAL BACKGROUND
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Who am I (education)?
• 1998-2000: Hogeschool Gent (BE)– BS Computer Sciences
• 2001-2005: Troy State University (US)– Exchange program
• Developed an interest in using ComS to help (molecular) biologists
– MS Biological Sciences• Research in yeast genetics with Dr. Christi Magrath (NSF fellowship)
• 2005-2010: Iowa State University– PhD Bioinformatics & Computational Biology
Education
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Who am I (professional)
Professional
• 2000-2001: Becton Dickinson• 2010-2013: HistoGeneX
• Section head Data Management & Bioinformatics
• 2012-now: Pathomation• Chief Technology Officer
• 2014-Q1 2017: VUB• Digital Pathology Manager
• 2016-now: HistoGeneX• Data scientist
WHAT IS DIGITAL MICROSCOPY?
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This is not it
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Digital microscopy on a budget
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Add a camera “port”
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Add more automation
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Whole slide imaging (single slide)
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Whole slide imaging (clinical)
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WSI needs hardware and software
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Hardware
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Software
Very large
image!
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How big are these images?
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When you get someone to scan your slides…
Enhanced network infrastructure
I gave you slides; how do I get to
see these?
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You have a hard time getting them back!
• You go to a website• You download a .sis-file• Which is not recognized by your browser• Then you go to the scanner vendor’s website• You download their free (but proprietary) viewer• You install the viewer (do you have rights to do that?)• You re-download the .sis-file• You open the .sis-file in the locally installed viewer• Sometimes the viewer is unstable and crashes– that’s normal; just start over
• Re-do this procedure on every device that you use– You just can’t do it on a Mac!
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Confusing your end-users (customers)! NOT good!
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Confusing your end-users (customers)! NOT good!
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What’s the solution?
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Digital microscopy at the VUB
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What does the Pathomation software look like?
(DIGITAL) PATHOLOGY 101
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What does a pathologist do?
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Tools for pathologists
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Digital tools for pathologists
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Digital (r)evolution
COMPANION DIAGNOSTICS
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The cost of cancer drugs
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How do cancer drugs work?
• Rituximab, Rituxan: – monoclonal Ab that attacks CD20+ B cells– Leukemia, lymphoma
• Trastuzumab, Herceptin– Interferes with Her2/Neu receptor– Breast cancer
• Imatinib, Gleevec– Tyrosine Kinase Inhibitor– Chronic Myelogenous Leukemia (CML), Gastrointestinal
tumors (GITs)• Everolimus, Afinitor– HR+ (ER or PR), Her2 negative– Breast cancer
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To prescribe or not to prescribe?
• Expensive drugs only work in a subset of patients– Herceptin: 20-30% of early stage breast cancer
• Only to be used in HER2/Neu positive patients• Cost: $4,659 / month
– Affinitor: 35% of patients respond • Only to be used in Her2 negative, HR positive patients• Cost: $8,701 / month
– Ibrance: • Only to be used in ER positive, Her2 negative• Also for metastatic cancer• Cost: $10,677 / month
– Avastin + Erbitux• Triple Negative Breast Cancer (TNBC)• Cost: $5,551 + $11,862
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The need for personalized medicine
Cancer therapy
Resection
Radio therapy
Targeted
Immune therapy
Research
Chemotherapy
% patients responding: 25%
20-30% patients benefits from ipilimumab
EpigeneticsCombinations
Lung cancer :EGFR - gefitinibALK - crizotinib
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So what do you do?
• Companion diagnostics are tests that are administered to assess what treatment is suited for a particular patient– Can save lots of resources (time, money), and therefore
lives– cDX is usually done on a (liquid) biopsy or resection
• Which means a pathologist is involved– Allows clinician to take shortcuts!
• Sometimes a 3rd line treatment can be opted for directly as a 1st line treatment
– Paves the way for personalized medicine• Get the right drug to the right patient at the right time • (at the right price for the patient and for society)
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A breast cancer panel
• Immunohistochemical stains– Assess the presence of specific molecules (proteins) in
cells (see Dr. Cohen for more info )– E-CAD: loss of E-cadherin function is often associated with
tumor progression and transition to more invasive disease– Ki67: aggressiveness (assess speed of cell division)– Hormone Receptors (Progesterone, Estrogen)– HER2/Nue Receptor
• See http://histosrv.vub.ac.be/cases2/scen03/#0,3• See http://histosrv.vub.ac.be/cases2/scen03/#8,18 • Determine the therapy based on the outcome of the various
immunohistochemical stains
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How can digital microscopy help?
• In the future: Automatic assessment of stained slides– Decision support systems– Most importantly: help troubleshoot borderline
cases!• Today: Training the pathologist for make the right assessment– http://training.Pathomation.com
• Today: Facilitate discussion– Tumor boards, multidisciplinary oncological consults– Second opinions
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The stakes are high!
128B market cap / 83B market cap
IN CLOSING
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Conclusions
• Digital pathology is ready for prime time– Education and training, – Research (including biobanking)
• DIY digital pathology– Do your due diligence: hardware AND software– DON’T spend all your resources on “stuff”• Hire the right people to implement the right workflows
– Start with one use case, expand to others– Spread the word and share experiences• Digital Pathology Association, International Academy of
Digital Pathology, European Society of Pathology…
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Learn more about digital pathology
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