gevolgen van path project voor nsclc - zorg … van path project voor nsclc hoe tillen we...
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10de avondsymposiumGroningen, 1 november 2017
Nieuwe ontwikkelingen in de behandeling van NSCLCGevolgen van PATH project voor NSCLC
Hoe tillen we Moleculaire Diagnostiek van NSCLC naa r hoger plan ?
Ed Schuuring
KMBP (Klinisch Moleculair Bioloog in de Pathologie) voor Pathologie van UMCG, Friesland, Hoogeveen, Zwolle en Martini/Winschoten
Head Laboratory Molecular Pathology, UMCG Groningen
DisclosuresConsultant/Advisory Board:
AstraZeneca, Roche, Pfizer, Novartis, Amgen, BioCartis, QCMD, ESP, IQNPATH, Cancer-ID
Speaker’s fee:Abbott, Novartis, Roche, Biocartis, Illumina
Grants/Sponsoring:Pfizer, Biocartis, BMS, Roche, Boehringer Ingelheim
Stock/Royalties:None
All transferred to UMCG-account
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Molecular profiling of lung cancer in 2017Molecular Pathology
Li JCO 2013
To define which patients for what drug benefit most (personalised therapy)
Wild type
del746-750
Traditional histopathological classification
>2009: Molecular Tumor Profiling
“1st”
“last”
5% neoplastic cells
>50% neoplastic cells
Images with courtesy of Erik Thunnissen, VUMC
This example represents a typical biopsyin our clinical practice (lung cancer)
NGS analysisToday’s tissue-management lung cancer (2017)
Presentation Ed Schuuring, 1 November 2017, Hoogkerk
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More analysis from one biopsy?Today’s tissue-management lung cancer (2017)
HE first
HE last
Diagnostic stain TTF1
DNA isolation NGS mutation analysis
RNA isolation MET exon skipping
Diagnostic stain mucin
Diagnostic stain P63/p40
ALK IHCNTRK FISH
ROS1 FISHRET FISH
MET FISHNGR1 FISH
Presentation Ed Schuuring, 1 November 2017, Hoogkerk
Turn-around-time (TAT) and hands-on-time
PD-L1 IHC
Molecular Pathology of lung cancer:
Optimal molecular testing
In Northern part of the Netherlands
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Next Generation Sequencing: Ion Torrent Personal Genome Machine (PGM)
• >50 hotspot regions in 24 genes (83 amplicons) (UMCG-PGM-v02b panel) for mutation screening in lung cancer, melanoom, colon carcinoma, GIST
• TAT: ~4-5 days (2 runs per week)
Molecular Oncological Pathology at UMCG: www.MolOncoPath.nl
AKT1_17 ESR1_534-537 KIT_exon11 MET exon 14-intron 14
ALK_1151-1156 GNA11_183 KIT_exon13 MET intron 13-exon 14
ALK_1174-1206 GNA11_209 KIT_exon14 NRAS_117-146
ALK_1269-1275 GNAQ_183 KIT_exon17 NRAS_12-13
BRAF_600 GNAQ_209 KIT_exon18 NRAS_61
BRAF_exon11 GNAS_201 KIT_exon8 PDGFRA_exon12
EGFR_492 GNAS_227 KIT_exon9 PDGFRA_exon14
EGFR_exon18 H3F3A_27-36 KRAS_117-146 PDGFRA_exon18
EGFR_exon19 H3F3B_35-37 KRAS_1213 PIK3CA_1047
EGFR_exon20 HRAS_117-146 KRAS_61 PIK3CA_542-549
EGFR_exon21 HRAS_1213 MAP2K1_111-124 POLE_286
ERBB2_exon19 HRAS_61 MAP2K1_203 POLE_411
ERBB2_exon20 IDH1_132 MAP2K1_264 ROS1_2032
ERBB2_exon21 IDH2_140-172 MAP2K1_382 ROS1_2155
ESR1_463 JAK2_617 MAP2K1_53
(inclusief MET-exon14-skipping en gatekeeper ROS/ALK mutatie)
Predictive markers testing using in-situ-hybridization (FISH)ISH-based detection methods for rearrangements, deletions, CNV/amplication of clinical relevant targeted genes (UMCG/2016)
BRISH HER2
Polysomy ALK
Amplification HER2
Break-apart ALK
Polysomy MET
Amplification FGFR1
amplification MET
Break-apart ROS
Break-apart RET
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Long AJSP 2012
Predictive markers testing using immunohistchemistryAntibodies specific for clinical relevant proteins of mutated targeted genes (UMCG/2017)
Specifiek IHC tegen
BRAF-V600E
FISH-ALK-positief
FISH-ALK-negatief
Specifeke IHC voor ALK-breuk
Positieve NSCLC
1+ 2+ 3+
MET-IHC
0-3 score
Specifiek anti-
exon19-del IHC
Specifiek anti-
L858R-del IHC
Kozu Lung cancer 2011
Methods to detect predictive molecular aberrations in Molecular Pathology of lung cancer (2017)
NGS-mutation: EGFR, ALK, ROS, RET, KRAS, BRAF, PIK3CA, MET, KIT
FISH-rearrangement: ROS, RET, (ALK), NTRK1, NGR1
FISH-amplification/CNV: MET, HER2, FGFR1, EGFR1
IHC: HER2, ALK, ROS1, PD-L1
RTPCR: MET exon14-skipping
Molecular Oncological Pathology at UMCG: www.MolOncoPath.nl
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Molecular diagnostics of lung cancer for treatment planning using gene-targeted therapy in NL
dutch guidelines
In 2007: starting with EGFR-mutation screening
In 2013: Dutch guideline in NSCLCOnly EGFR-mutation analysis
In 2013: ALK-translocation (Registration crizotinib July 2012)
In July 2015: revisited Dutch guideline for NSCLC:(1) EGFR, ALK; (2) HER2, BRAF, RET and ROS1
Dutch Oncoline guideline for NSCLC (July 2015):(1) EGFR, ALK; (2) HER2, BRAF, RET and ROS1
CAP-IASLC-AMP guideline for NSCLC (Aug 2017) (Hanna JCO 2017)
EGFR, ALK, ROS and PD-L1 (recommendation HER2, BRAF and RET)
NCCN guideline for NSCLC (2016) for adca and never-smokers SCC
(1) EGFR, ALK; (2) as part of broad profiling (HER2, MET, BRAF, RET, ROS1)
ESMO guideline for NSCLC (2013/2016) (Kerr Ann Oncol 2013; Novello, 2016)
co-testing EGFR and ALK (recommend KRAS, BRAF, HER2 and ROS1)
Molecular diagnostics of lung cancer for treatment planning using gene-targeted therapy
international guidelines
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Studie Fase Type tumor Doel
NVALT 15 III plano - FGFR1 Stadium IIIB/IV met FGFR1 amp: nintedanib
NVALT-17 III adeno - EGFR mut 1e lijn intercalated vs erlotinib NVALT-19 II mesothelioom 1e lijn maintenance gemcitabine na chemotherapie (cis/pem)
IL-09 plano 1e lijn carbo/taxol/orale fosfoinositide 3-kinase remmer
LO-41 II plano HER3 remmer + carbo/taxol LO-45 I/II SCLC - Extensive disease PARP remmer + carbo/etoposide LO-24 II adeno - BRAF mutatie V600E 1e lijn stadium IV. BRAF/MEK remmer
LO-27 III adeno - ALK translocatie 1e lijn LDK of cisplatine/pemetrexed LO-36 II adeno - ALK translocatie LO-36 II adeno - ALK translocatie LO-40 II adeno –EGFR mutatie T790M+ 2e lijn: stadium IV bij EGFR resistentie: 3e generatie TKI
LO-48 Ib/II adeno - EGFR + c-MET amp.; geen T790M
2e/3e lijn: c-MET remmer + gefitinib
LO-54 III adeno - EGFR mutatie +/- T790M 3e en volgende lijnen; 3e generatie EGFR remmer vs chemotherapie, cross over mogelijk na chemotherapie
CompassionateUse
Ceritinib NSCLC –EML4-ALK Bij resistentie voor crizotinib Alectinib NSCLC – EML4-ALK Bij geen behandelopties meer voor ALK+ patienten
Nivolumab NSCLC - plano & adenocarcinoom 2e lijns therapie na platinum doublet
Sunitinib NSCLC - PDGFR mutatie indien PDGFR mutatie aanwezig na platinum doublet
Sunitinib NSCLC - RET translocatie indien RET translocatie aanwezig na platinum doublet
Nieuwe predicitieve biomarkers in kader van klinische trials bij longkanker in umcg (www.moloncopath.nl/longziekten)
Bezocht op 24022017
Molecular Pathology of lung cancer in UMCG and North-Netherlands (2017)
NGS-mutation: EGFR, ALK, ROS, RET, KRAS, BRAF, PIK3CA, MET, KIT
FISH-rearrangement: ROS, RET, (ALK), NTRK1, NGR1
FISH-amplification/CNV: MET, HER2, FGFR1, EGFR1
IHC: HER2, ALK, ROS1, PD-L1
RTPCR: MET exon14-skipping
Molecular Oncological Pathology at UMCG: www.MolOncoPath.nl
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Uitdagingen mbt moleculaire pathologie in PA-labs in Nederland in 2017
• Verschillende moleculaire predictieve markers
• Verschillende moleculaire detectiemethoden
• Geen/weinig informatie over huidige behandelmethoden
• Geen gestandaardiseerde verslaglegging
• Kosten spelen rol bij keuze (uitgebreidheid) testen
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national consortium of >38 pathology-labs, medical oncologists, pulmonologists, NVALT, NVMO, NVVP, PALGA
Goal: To introduce a NGS assay to create optimal and equal access to targeted therapies for all (lung, melanoma, GIST, CRC) cancer patients in the Netherlands
Project PATH (Predictive Analysis for THerapy)
Optimizing access to personalized cancer therapy in the
Netherlands; from tissue to therapy.
CALL ZONMW GGG: PERSONALISED MEDICINE – ONCOLOGY
http://www.netwerk-path.nl
elke patiënt de juiste uitslag en advies
Project PATH (Predictive Analysis for THerapy)
Optimizing access to personalized cancer therapy in the
Netherlands; from tissue to therapy.
Het doel van het PATH-project:
• Optimalisatie van predictieve diagnostiek>> leren van best practices >> samen naar nog betere diagnostiek
• Standaardisatie van rapportage en interpretatie van moleculaire resultaten>> in PALGA >> allemaal dezelfde taal spreken
• Inrichten van multidisciplinair expertise netwerk van moleculaire tumorboards>> samen naar betere vertaling naar de kliniek >> therapie op maat
• Opzetten infrastructuur voor (toekomstig) Health Technology Assessment (HTA) onderzoek>> Effectiviteit organisatie van predictieve moleculaire diagnostiek>> Kosteneffectiviteit moleculaire testen
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WP 2Ed Schuuring , Petra Nederlof, Bastiaan Tops, Astrid Eijkelenboom
Veerle Coupé ; Eddy Adang; Erik Thunnissen
WP 3Harry Groen ;Hans Gelderblom; Katrien Grünberg
WP 4Stefan Willems ; Henk-Jan van Slooten; Paul Seegers
WP 1Marjolijn Ligtenberg ;Katrien Grünberg
Predictive gene Aberrations Cancer type Targeted agent
ALK SNVs, Fusion-transcript Lung Crizotinib, Ceritinib
BRAF SNVs Skin (melanoma) Vemurafenib
EGFR SNVs Lung Gefitinib, erlotinib
ERBB2 (Her2) amplification Breast Trastuzumab
KIT SNVs GIST Imatinib, Sorafenib
KRAS SNVs Colon Cetuximab, Panitumumab
NRAS SNVs Colon Cetuximab, Panitumumab
PDGFRA SNVs GIST Imatinib, Sorafenib
ROS1 Fusion-transcript Lung Crizotinib, Ceritinib
BRCA1 SNVs, CNVs Ovary Olaparib
BRCA2 SNVs, CNVs Ovary Olaparib
List of predictive genetic biomarkers and accompanying
targeted agents that are currently (2017) approved for
treatment of solid tumours in The Netherlands
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PATH-WP2 task forcegene-panel (2017 – for implementation)
• Clinical relevant: direct impact on targeted therapy:> Dutch (concept) onco-guidelines> Ongoing Dutch clinical trials> Information from pharma (2017/drup-study)> literature
• Lung cancer, CRC, GIST and melanoma• Variants (mutations, deletions, fusions, CNV)
Design mutation/gene panel: Leon van Kempen, Leonie Kroeze, Bas Tops, Arja ter Elst, Ed SchuuringsmMIP-design/validation: Leonie Kroeze, Astrid Eijkelenboom, Marjolijn Ligtenberg
PATH-v02D DNA gene panel(Oct 2017: implementatie in 4 centers using smMIP-NGS)
Predictive gene Aberrations Predictive gene Aberrations
AKT1 SNV JAK2 SNV
AKT2 SNV KIT SNV + CNV
AKT3 SNV KRAS SNV + CNV
ALK SNV + CNV MAP2K1 SNV
ARAF SNV MDM2 CNV
BRAF SNV + CNV MET SNV + CNV
DDR2 SNV MTOR SNV
EGFR SNV + CNV NRAS SNV
ERBB2 SNV + CNV PDGFRA SNV + CNV
FGFR1 CNV PIK3CA SNV
FGFR2 CNV POLE SNV
FGFR3 CNV PTEN SNV
GNAS SNV RAF1 SNV
GNAQ SNV ROS1 SNV
GNA11 SNV TP53 SNV + CNV
HRAS SNV
IDH1 SNV MSI
IDH2 SNV AMELX/Y
Consortium (Dutch University Laboratories of Molecular Pathology)Consensus on NGS mutation panel > each patient in NL receives same opportunities for therapy
http://www.netwerk-path.nl
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Hiatt JB, et al. Genome Res. 2013 May;23(5):843-54
Single molecule Molecular Inversion Probes for NGS PATH-panel
single molecule tag
Single molecule tag to identify independent biological template molecules:Higher specificityHigher sensitivity
Molecular Pathology of lung cancer in UMCG and North-Netherlands (2017)
NGS-mutation: EGFR, ALK, ROS, RET, KRAS, BRAF, PIK3CA, MET, KIT
FISH-rearrangement: ROS, RET, (ALK), NTRK1, NGR1
FISH-amplification/CNV: MET, HER2, FGFR1, EGFR1
IHC: HER2, ALK, ROS1, PD-L1
RTPCR: MET exon14-skipping
Molecular Oncological Pathology at UMCG: www.MolOncoPath.nl
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PATH-RNA-gene panel: gene-composition (in development)
Predictive gene Aberrations
NTRK1 Fusion-transcript
MET Exon 8/14 skipping
EGFR Viii deletion
ALK Fusion-transcript
FGFR3 Fusion -transcript
BRAF Fusion-transcript
RET Fusion-transcript
ROS1 Fusion-transcript
PDGFRA Fusion-transcript
NRG1/FGFR1 ? Fusion-transcript
Consortium (Dutch University Laboratories of Molecular Pathology)Consensus on NGS mutation panel > each patient in NL receives same opportunities for therapy
http://www.netwerk-path.nl
RNA-based assays to detect fusionscommercial kits becoming available now
• ALK RGQ RT-PCR kit (Qiagen)• Ion AmpliSeq RNA fusion Lung Cancer Panel (Life Techn) (RUMC, DNA, LUMC)• EML4-ALK Fusion Gene Detection Kit (Amoy Diagnostics)• EML4-ALK Fusion Gene Detection Kit (Entrogen)• RNA-seq (NGS-approach; ???)• nCounter Nanostring Lung Panel (UMCG/NKB)• RNA SPET Panel Nugen (UMCG/NKB)• Archer Fusionplex CTL Panel (NKI, Erasmus, LUMC)Lung Cancer• Lung Cancer Qiaseq Targeted RNAscan panel (RadboudMC)
� Validated in 4 PATH-labs on same samples (what test should we use ?)� in single run “all” fusions tested (cost-effective)� possibility to add targets (NGR1, MET-skipping)� Validate predictive value to select good responders� RNA vs DNA from FFPE-tissue
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RNA-based assays to detect fusionsfor ALK, RET, NTRK AND ROS
nanostring UMCG (first data)
2/2 RET-fusions; 3/3 ALK-fusions; 3/3 ROS-fusions; 4/4 negative controls
Next-step: ad NGR1 and MET-exon14 skipping
University of Alabama Comprehensive Cancer Center R esearch Retreat, Birmingham, AL, October 6, 2014
Molecular results might as well be ……hieroglyphs
ALK, APC, ASXL1, ATM, BAP1, BCR-ABL, BRAF, BRCA1, BRCA2, CEBPA, CRAF (RAF1), CSF1R, CTLA4,CTNNB1, DDR1, DNMT3A, ERBB1 (EGFR), ERBB2 (HER2), ESR1, FGFR4, FLT3, IDH1, IDH2, JAK2, KIT, KRAS, MAP2K1 (MEK1), MAP2K2 (MEK2), MAPK3 (ERK1), MET, MLL (KMT2A), MPL (TPOR), MYC, MYD88, NOTCH1, NPM1, NRAS, PARP1, PDGFRA, PDGFRB, PIK3CA, PML, PTEN, PTPN11, RARA, RB1, RET (MEN2), RUNX1, TET2, TP53, VEGFA, VEGFR1 (FLT1), VEGFR2 (KDR), VEGFR3 (FLT4), VHL, WT1, mTOR
List of actionable
cancer biomarkers, 2015 AD
Hieroglyphs on stone
tablet, 5000 BC
Courtesy of Mark Bogulski, MD, Genome Health Solutions
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Nation wide Digital Pathology Database (since 1991)
Courtesy of S. Willems, UMCU
Standarization of molecular data (NGS) reporting> launching first molecular-module (KRAS, EGFR, BRAF) (dec 2015)
> launching molecular-module for NGS data (oct 2017)> linking to clinical databases and registries (2018)
Options for Quality-control, TAT, identifying rare mutation, etc
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• Example: NSCLC with EGFR: c.2281G>A; p.(D761N)
• Example: NSCLC with PIK3CA: c.3140A>G; p.(H1047R)
• Example: NSCLC with PIK3CA: c.3140A>G; p.(H1047R) 80% and p(L858R) 35%
• Example: AKT3 amplificatie 80%, EGFR amplificatie 50%, KRAS amplificatie 20%, TSC1 A944T mutatie 10%, MDM2 amplificatie 7%, MCL1 amplificatie 3%, TP53 Y234C mutatie 2%, EPHA5 A454N mutaties 1%, MYST3 amplificatie 1%
Reporting Mutation Analysis dataHandling of unexpected, difficult, rare mutations?
Treatment options ?
Btumortype
genenset
NGS analyse
moleculaire tumor board
tumorspecifieke verandering
gen a gen b gen c, mut X gen b
analyse en moleculaire interpretatie
A C DC D
A B C D
behandelingop maat
analyse en moleculaire interpretatie
Regulier MDO
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Btumortype
genenset
NGS analyse
Moleculaire Tumor Board
tumorspecifieke verandering
gen a gen b gen c, mut X
analyse en moleculaire interpretatie
A C DC D
A B C D
behandeling op maat
gen b
Regulier MDO
Interpretation of Mutation Analysis DataHandling of unexpected, difficult, rare mutations?
Treatment options/advice ?
Using 3D-modeling, drug designand predicting interaction
Groningen Research Institutefor Pharmacy (drug design)
(1) KMBP/pathologist search for information on general treatment advice and interpretation in PA-report(2) assistance with specific treatment advice via the Molecular Tumor Board Groningen (every Friday MTB-meeting)(3) Using databases, variant calling, 3-D modelling
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Every Friday from 1400-1500 hrs we discuss requests for advice (since Nov 2014)
www.moloncopath.nl
Molecular Tumor Board Groningen (in dutch)
Prof dr Ed Schuuring, KMBPDr Arja ter Elst, KMBPProf dr Anke van den Berg, KMBPDr Nils ’t Hart, lungpathologistProf dr Wim Timens, lungpathologistProf dr Harry Groen, pulmonologistDr Jeroen Hiltermann, pulmonologistDr Anthonie van der Wekken, pulmonologistProf dr Geke Hospers, medical oncologistDr Hilde Jalving, medical oncologistDr Matthew Grover, drug-design pharmocologistDr Leon van Kempen, KMBP-traineeDr Maarten Niemantsverdriet, KMBP-trainee
This expert forum combines the expertise of clinical molecular biologists in pathology, pathologists, medical oncologists, molecular pharmacologist and pulmonologists
Verslaglegging mutatieanalysemoleculaire interpretatie
Materiaal (FFPE-blokje) ontvangen voor consult van MZH (MZH:T00-0000-II1).
Moleculaire interpretatie (UMCG):Er is een mutatie aangetoond in EGFR: c.2573T>G; p.(L858R).Er zijn geen mutaties waargenomen in de andere mutatie-hotspots in EGFR, BRAF, KRAS, ERBB2 (HER2), KIT, ALK, NRAS, PDGFRA en PIK3CA.
Klinische interpretatie:Longcarcinomen (met name NSCLC) met een activerende mutatie in EGFR reageren in het algemeen goed op therapie gericht tegen EGFR. Indien u een behandeladvies of informatie wenst over lopende trials, kunt u contact opnemen met onze Moleculaire Tumor Board via [email protected] (zie www.MolOncoPath.nl).
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Moleculaire Tumor Board in UMCG en regio-Noord
Jos Stigt, Saskia Offermans, Clemens Prinsen (Isala, Zwolle)
PATH Expert netwerk• Netwerk van Moleculaire Tumorboards (MTBs)
• Vertaling moleculaire info naar behandeladviezen
• Terugkoppeling naar moleculaire database
• Faciliteert toegang tot klinische trials
• Nationaal expert platform
• Casusoverleg
• ICT infrastructuur voor delen van informatie en decision support tools
• Contact met farma, CPCT, gezondheidsautoriteiten, etc
� Harmonisatie mbt interpretatie, advies en rapportage� Gedeelde database (variant/advies/respons)� Landelijke database (overview observed variants and biology)
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Landelijkplatform
predictievediagnostie
k
Hub
Noordoost
Hub
Noordwest
Hub
Midden
Hub Zuidwest Hub
Middenwest
Hub
Zuid
Hub
Oost
CMDP
NVALT
BOM
CPCTFarma
Path
Path
Path
Path
Path
Path
Path
Path
Path
Path
Path Path PathPathPath Path
Path Path
Path
Path
Path
Path
Path
Path
Path
Path
Path
Path
PALGA
Trial alert
Pharma Scientific socsCPCT
Proposal to organise national program for optimal targeted treatmentTo exchange info on experience, training, education, ongoing trials
All hospitalsRegional hubsInteraction with important stakeholders
Regional Molecular Tumor BoardsNational tumor board ForumLinking PA with clinical databases
Noord-oost
HUB
management UMCG
PA
UMCG
Groningen
PA
Martini Groningen
PA
Isala
Zwolle
PA
Enschede
PA
TREANT
Hoogeveen
PA
Friesland
Leeuwarden
Moleculaire Pathologie in de regio Noord
Project PATH (Predictive Analysis for THerapy)
Optimizing access to personalized cancer therapy in
the Netherlands; from tissue to therapy.
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Noord-oost
HUB
Coordination UMCG
PA
UMCG
Groningen
PA
Martini Groningen
PA
Isala
Zwolle
PA
Enschede
PA
TREANT
Hoogeveen
PA
Friesland
Leeuwarden
Moleculaire Pathologie in de regio Noord
Noordelijk Netwerk voor Moleculaire Pathologie:
• Afstemming met pathologen en oncologen• Zelfde pakket aan MD-testen• Vergelijkbare zorg voor elke patient• Centrale MD-testen (complexe assays)• Lokale testen (voor lage TAT)• Kosten-effectiviteit• Kwaliteit• Regionaal overleg, bijscholing met oncologen• Scholing voor AIOS
2017:• UMCG centrale Moleculaire Tumor Board (nov 2014)• Lokale boards binnen netwerk• Bij-/nascholing pathologen/oncologen
Predictive molecular testing anno 2017
Patient with cancer ?
liquidbiopsy
Molecularprofiling
diagnosis
Molecularprofiling
diagnosis
tissuebiopsy
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Can peripheral blood be used to determine the presence of the tumor ?
Plasma:
* DNA and circulating tumor DNA (ctDNA)* RNA and circulating tumor RNA (ctRNA)* Proteomic/immunological tumor markers* Pharmacokinetics ([drug])
Leukocytes and circulating tumor cells (CTC) Platelets and tumor RNA
Mutatie testen UMCGFFPE-biopten met >2% neoplastische cellenCirculerend tumor DNA in celvrij plasma
EGFR-T790M bij resistentie TKI (tagrisso/osimertinib)
• FDA-approved for EGFR-T790M-positive cases ( nov 2015)
• EU-approved for EGFR-T790M-positive cases (feb 2016)
• FDA-approved T790M-test cobas-EGFR-mutation test v2 (nov 2015; UMCG ref-lab for NL)
EGFR-del19/L858R voor behandelkeuze
• Dutch onco-guideline (july 2015)
• UMCG-ISO15189-validated ddPCR EGFR mutation test
BRAF-V600E voor behandelkeuze/monitorig melanoom
KRAS-common voor behandelkeuze/monitoring CRC
KIT-exon 11 voor behandelkeuze/monitoring GIST
extra kosten, snellere TAT, meer biopten met uitslag (beperkt genen), andere logistiek
EGFR-plasmatest: logistiek aanvragen op www.moloncopath.nlVia apart extern plasma-aanvraagformulier
Op verzoek versturen we pakket met info, formulier en bloedbuizen)
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Molecular Pathologie UMCG-teamMD-technicians:• Ingrid de Boer-Huitema• Annelies ten Caat• Erik Nijboer• Paskal van Norel• Rianne Pelgrim• Inge Platteel• Martin Schipper• Jantine Sietzema• Tom Artz• Frank Scherpen• Klaas Kooistra
Molecular Tumor Board Groningen (in dutch)Ed Schuuring, KMBPArja ter Elst, KMBPAnke van den Berg, KMBPNils ’t Hart, lungpatholoogWim Timens, lungpatholoogHarry Groen, pulmonologistJeroen Hiltermann, pulmonologistAnthonie van der Wekken, pulmonologistGeke Hospers, medisch oncologistLucy Hijmering-Kappelle, pulmonologistHilde Jalving, medisch oncoloogSjoukje Oosting, medisch oncoloogMathew Glover, drug-design (GRI of Pharmacy)Maarten Niemantsverdriet, KMBPioLeon van Kempen, KMBPio
Saskia Offermans, pathologist IsalaClemens Prinsen, KMBP IsalaJos Stigt, pulmonologist Isala
Gallop-studie: Pieter Boonstra, Marco Tibbesma, Arja ter Elst, Ed Schuuring, An ReynersPATH-consortiumNVALT-plasma-studies: Lisestte Bosman, Arja ter Elst, Harry Groen, Ed Schuuring
KMBP:•Elise van der Logt (PAF, UMCG)•Arja ter Elst•Anke van den Berg•Ed Schuuring (UMCG, HGV, MZH, PAF, Isala)•Maarten Niemantsverdriet (KMBPio 2016-2020) (Isala, UMCG)•Leon van Kempen (KMBPio 2016-2018)
Pathologists:•Wim Timens•Nils ‘t Hart•Arjan Diepstra (moleculaire patholoog)