the role of biomolecular analysis to determine glioma ... · c-d. he infiltrasi leptomening dan...
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The Role of GliomaBiomolecular Analysis to Determine Diagnosis and
Prognosis
Muhammad Kamil MD PhD
BRAIN TUMOR
SEL SARAF + SEL SEL PENYANGGA (GLIA)
NEURON
ASTROSIT
OLIGODENDROSIT
MIKROGLIA
SEL SARAF + SEL SEL PENYANGGA (GLIA)
NEURON
ASTROSIT
OLIGODENDROSITMIKROGLIA
NEOPLASIA
TUMORGLIA
Key Points
bull Klasifikasi WHO terbaru untukTumor Saraf Pusat (2016)
bull Penegakan diagnosis klinis
bull Future direction
Klasifikasi WHO untukTumor Saraf Pusat
2016
Klasifikasi WHO untuk Tumor Otak 2016
19791988
19932007
2016
2007
2016
IDH
2007 2016
80rsquos 90rsquos
= BIOLOGY MOLECULAR ANALYSIS
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final
lengkap2 berdasar histologi3 grading 4 molecular
characteristicsActa Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final lengkap2 berdasar histologi3 grading 4 molecular characteristics
Contoh
Anaplastic astrocytoma WHO grade III IDH-wild type
1
2 3 4
( 2007 Anaplastic astrocytoma WHO grIII )
Diffuse infiltrating glioma
bull Diffuse astrocytoma Diffuse astrocytoma WHO grade II
IDH-mutantGemistocytic astrocytoma WHO grade II IDH-mutant
Diffuse astrocytoma WHO grade II IDH-wild type
Diffuse astrocytoma WHO grade II NOS
Anaplastic astrocytoma WHO grade III IDH-mutant
Anaplastic astrocytoma WHO grade III IDH-wild type
Oligodendroglioma Oligodendroglioma WHO grade II
IDH-mutant and 1p19q-codeletion Oligodendroglioma WHO grade II
NOS
Anaplastic Oligodendroglioma WHO grade III IDH-mutant and 1p19q-codeletion
Anaplastic Oligodendroglioma WHO grade III NOS
Oligoastrocytoma NOS Anaplastic Oligoastrocytoma NOS
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Diffuse infiltrating glioma (2)
bull Glioblastomasbull Glioblastoma IDH-wild type
Giant cell glioblastoma
Gliosarcoma
Epithelioid glioblastoma
bull Glioblastoma IDH mutant
bull Glioblastoma NOS
bull Diffuse midline Glioma H3 K27M-mutant
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
IDH
Deregulation of IDH enzymatic activity is associated with human disease
Serena Tommasini-Ghelfi et al Sci Adv 20195eaaw4543
Copyright copy 2019 The Authors some rights reserved exclusive licensee American Association
for the Advancement of Science No claim to original US Government Works Distributed
under a Creative Commons Attribution NonCommercial License 40 (CC BY-NC)
IDH MUTATION VS IDH WILD TYPE
GLIOMA
Science 2008An integrated genomic analysis of human glioblastoma multiformeParsons DW1 Jones S Zhang X Lin JC Leary RJ Angenendt P Mankoo P Carter H Siu IM Gallia GL Olivi A McLendon R Rasheed BA Keir S Nikolskaya T Nikolsky Y Busam DA Tekleab H Diaz LA Jr Hartigan J Smith DR Strausberg RL Marie SK Shinjo SM Yan H Riggins GJ Bigner DD Karchin R Papadopoulos N Parmigiani G Vogelstein B Velculescu VE Kinzler KW
IDH1 amp IDH2
J NeurosurgTumor cell-specific chromosomal abnormality in the vascular endothelial cells of anaplastic oligodendrogliomaJiang H1 Zhang Z1 Ren X1 Zeng W1 Wang J2 Lin S1
1p19q co-deletion
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what else
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what to check
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
BRAIN TUMOR
SEL SARAF + SEL SEL PENYANGGA (GLIA)
NEURON
ASTROSIT
OLIGODENDROSIT
MIKROGLIA
SEL SARAF + SEL SEL PENYANGGA (GLIA)
NEURON
ASTROSIT
OLIGODENDROSITMIKROGLIA
NEOPLASIA
TUMORGLIA
Key Points
bull Klasifikasi WHO terbaru untukTumor Saraf Pusat (2016)
bull Penegakan diagnosis klinis
bull Future direction
Klasifikasi WHO untukTumor Saraf Pusat
2016
Klasifikasi WHO untuk Tumor Otak 2016
19791988
19932007
2016
2007
2016
IDH
2007 2016
80rsquos 90rsquos
= BIOLOGY MOLECULAR ANALYSIS
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final
lengkap2 berdasar histologi3 grading 4 molecular
characteristicsActa Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final lengkap2 berdasar histologi3 grading 4 molecular characteristics
Contoh
Anaplastic astrocytoma WHO grade III IDH-wild type
1
2 3 4
( 2007 Anaplastic astrocytoma WHO grIII )
Diffuse infiltrating glioma
bull Diffuse astrocytoma Diffuse astrocytoma WHO grade II
IDH-mutantGemistocytic astrocytoma WHO grade II IDH-mutant
Diffuse astrocytoma WHO grade II IDH-wild type
Diffuse astrocytoma WHO grade II NOS
Anaplastic astrocytoma WHO grade III IDH-mutant
Anaplastic astrocytoma WHO grade III IDH-wild type
Oligodendroglioma Oligodendroglioma WHO grade II
IDH-mutant and 1p19q-codeletion Oligodendroglioma WHO grade II
NOS
Anaplastic Oligodendroglioma WHO grade III IDH-mutant and 1p19q-codeletion
Anaplastic Oligodendroglioma WHO grade III NOS
Oligoastrocytoma NOS Anaplastic Oligoastrocytoma NOS
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Diffuse infiltrating glioma (2)
bull Glioblastomasbull Glioblastoma IDH-wild type
Giant cell glioblastoma
Gliosarcoma
Epithelioid glioblastoma
bull Glioblastoma IDH mutant
bull Glioblastoma NOS
bull Diffuse midline Glioma H3 K27M-mutant
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
IDH
Deregulation of IDH enzymatic activity is associated with human disease
Serena Tommasini-Ghelfi et al Sci Adv 20195eaaw4543
Copyright copy 2019 The Authors some rights reserved exclusive licensee American Association
for the Advancement of Science No claim to original US Government Works Distributed
under a Creative Commons Attribution NonCommercial License 40 (CC BY-NC)
IDH MUTATION VS IDH WILD TYPE
GLIOMA
Science 2008An integrated genomic analysis of human glioblastoma multiformeParsons DW1 Jones S Zhang X Lin JC Leary RJ Angenendt P Mankoo P Carter H Siu IM Gallia GL Olivi A McLendon R Rasheed BA Keir S Nikolskaya T Nikolsky Y Busam DA Tekleab H Diaz LA Jr Hartigan J Smith DR Strausberg RL Marie SK Shinjo SM Yan H Riggins GJ Bigner DD Karchin R Papadopoulos N Parmigiani G Vogelstein B Velculescu VE Kinzler KW
IDH1 amp IDH2
J NeurosurgTumor cell-specific chromosomal abnormality in the vascular endothelial cells of anaplastic oligodendrogliomaJiang H1 Zhang Z1 Ren X1 Zeng W1 Wang J2 Lin S1
1p19q co-deletion
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what else
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what to check
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
SEL SARAF + SEL SEL PENYANGGA (GLIA)
NEURON
ASTROSIT
OLIGODENDROSIT
MIKROGLIA
SEL SARAF + SEL SEL PENYANGGA (GLIA)
NEURON
ASTROSIT
OLIGODENDROSITMIKROGLIA
NEOPLASIA
TUMORGLIA
Key Points
bull Klasifikasi WHO terbaru untukTumor Saraf Pusat (2016)
bull Penegakan diagnosis klinis
bull Future direction
Klasifikasi WHO untukTumor Saraf Pusat
2016
Klasifikasi WHO untuk Tumor Otak 2016
19791988
19932007
2016
2007
2016
IDH
2007 2016
80rsquos 90rsquos
= BIOLOGY MOLECULAR ANALYSIS
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final
lengkap2 berdasar histologi3 grading 4 molecular
characteristicsActa Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final lengkap2 berdasar histologi3 grading 4 molecular characteristics
Contoh
Anaplastic astrocytoma WHO grade III IDH-wild type
1
2 3 4
( 2007 Anaplastic astrocytoma WHO grIII )
Diffuse infiltrating glioma
bull Diffuse astrocytoma Diffuse astrocytoma WHO grade II
IDH-mutantGemistocytic astrocytoma WHO grade II IDH-mutant
Diffuse astrocytoma WHO grade II IDH-wild type
Diffuse astrocytoma WHO grade II NOS
Anaplastic astrocytoma WHO grade III IDH-mutant
Anaplastic astrocytoma WHO grade III IDH-wild type
Oligodendroglioma Oligodendroglioma WHO grade II
IDH-mutant and 1p19q-codeletion Oligodendroglioma WHO grade II
NOS
Anaplastic Oligodendroglioma WHO grade III IDH-mutant and 1p19q-codeletion
Anaplastic Oligodendroglioma WHO grade III NOS
Oligoastrocytoma NOS Anaplastic Oligoastrocytoma NOS
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Diffuse infiltrating glioma (2)
bull Glioblastomasbull Glioblastoma IDH-wild type
Giant cell glioblastoma
Gliosarcoma
Epithelioid glioblastoma
bull Glioblastoma IDH mutant
bull Glioblastoma NOS
bull Diffuse midline Glioma H3 K27M-mutant
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
IDH
Deregulation of IDH enzymatic activity is associated with human disease
Serena Tommasini-Ghelfi et al Sci Adv 20195eaaw4543
Copyright copy 2019 The Authors some rights reserved exclusive licensee American Association
for the Advancement of Science No claim to original US Government Works Distributed
under a Creative Commons Attribution NonCommercial License 40 (CC BY-NC)
IDH MUTATION VS IDH WILD TYPE
GLIOMA
Science 2008An integrated genomic analysis of human glioblastoma multiformeParsons DW1 Jones S Zhang X Lin JC Leary RJ Angenendt P Mankoo P Carter H Siu IM Gallia GL Olivi A McLendon R Rasheed BA Keir S Nikolskaya T Nikolsky Y Busam DA Tekleab H Diaz LA Jr Hartigan J Smith DR Strausberg RL Marie SK Shinjo SM Yan H Riggins GJ Bigner DD Karchin R Papadopoulos N Parmigiani G Vogelstein B Velculescu VE Kinzler KW
IDH1 amp IDH2
J NeurosurgTumor cell-specific chromosomal abnormality in the vascular endothelial cells of anaplastic oligodendrogliomaJiang H1 Zhang Z1 Ren X1 Zeng W1 Wang J2 Lin S1
1p19q co-deletion
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what else
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what to check
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
SEL SARAF + SEL SEL PENYANGGA (GLIA)
NEURON
ASTROSIT
OLIGODENDROSITMIKROGLIA
NEOPLASIA
TUMORGLIA
Key Points
bull Klasifikasi WHO terbaru untukTumor Saraf Pusat (2016)
bull Penegakan diagnosis klinis
bull Future direction
Klasifikasi WHO untukTumor Saraf Pusat
2016
Klasifikasi WHO untuk Tumor Otak 2016
19791988
19932007
2016
2007
2016
IDH
2007 2016
80rsquos 90rsquos
= BIOLOGY MOLECULAR ANALYSIS
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final
lengkap2 berdasar histologi3 grading 4 molecular
characteristicsActa Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final lengkap2 berdasar histologi3 grading 4 molecular characteristics
Contoh
Anaplastic astrocytoma WHO grade III IDH-wild type
1
2 3 4
( 2007 Anaplastic astrocytoma WHO grIII )
Diffuse infiltrating glioma
bull Diffuse astrocytoma Diffuse astrocytoma WHO grade II
IDH-mutantGemistocytic astrocytoma WHO grade II IDH-mutant
Diffuse astrocytoma WHO grade II IDH-wild type
Diffuse astrocytoma WHO grade II NOS
Anaplastic astrocytoma WHO grade III IDH-mutant
Anaplastic astrocytoma WHO grade III IDH-wild type
Oligodendroglioma Oligodendroglioma WHO grade II
IDH-mutant and 1p19q-codeletion Oligodendroglioma WHO grade II
NOS
Anaplastic Oligodendroglioma WHO grade III IDH-mutant and 1p19q-codeletion
Anaplastic Oligodendroglioma WHO grade III NOS
Oligoastrocytoma NOS Anaplastic Oligoastrocytoma NOS
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Diffuse infiltrating glioma (2)
bull Glioblastomasbull Glioblastoma IDH-wild type
Giant cell glioblastoma
Gliosarcoma
Epithelioid glioblastoma
bull Glioblastoma IDH mutant
bull Glioblastoma NOS
bull Diffuse midline Glioma H3 K27M-mutant
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
IDH
Deregulation of IDH enzymatic activity is associated with human disease
Serena Tommasini-Ghelfi et al Sci Adv 20195eaaw4543
Copyright copy 2019 The Authors some rights reserved exclusive licensee American Association
for the Advancement of Science No claim to original US Government Works Distributed
under a Creative Commons Attribution NonCommercial License 40 (CC BY-NC)
IDH MUTATION VS IDH WILD TYPE
GLIOMA
Science 2008An integrated genomic analysis of human glioblastoma multiformeParsons DW1 Jones S Zhang X Lin JC Leary RJ Angenendt P Mankoo P Carter H Siu IM Gallia GL Olivi A McLendon R Rasheed BA Keir S Nikolskaya T Nikolsky Y Busam DA Tekleab H Diaz LA Jr Hartigan J Smith DR Strausberg RL Marie SK Shinjo SM Yan H Riggins GJ Bigner DD Karchin R Papadopoulos N Parmigiani G Vogelstein B Velculescu VE Kinzler KW
IDH1 amp IDH2
J NeurosurgTumor cell-specific chromosomal abnormality in the vascular endothelial cells of anaplastic oligodendrogliomaJiang H1 Zhang Z1 Ren X1 Zeng W1 Wang J2 Lin S1
1p19q co-deletion
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what else
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what to check
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
NEOPLASIA
TUMORGLIA
Key Points
bull Klasifikasi WHO terbaru untukTumor Saraf Pusat (2016)
bull Penegakan diagnosis klinis
bull Future direction
Klasifikasi WHO untukTumor Saraf Pusat
2016
Klasifikasi WHO untuk Tumor Otak 2016
19791988
19932007
2016
2007
2016
IDH
2007 2016
80rsquos 90rsquos
= BIOLOGY MOLECULAR ANALYSIS
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final
lengkap2 berdasar histologi3 grading 4 molecular
characteristicsActa Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final lengkap2 berdasar histologi3 grading 4 molecular characteristics
Contoh
Anaplastic astrocytoma WHO grade III IDH-wild type
1
2 3 4
( 2007 Anaplastic astrocytoma WHO grIII )
Diffuse infiltrating glioma
bull Diffuse astrocytoma Diffuse astrocytoma WHO grade II
IDH-mutantGemistocytic astrocytoma WHO grade II IDH-mutant
Diffuse astrocytoma WHO grade II IDH-wild type
Diffuse astrocytoma WHO grade II NOS
Anaplastic astrocytoma WHO grade III IDH-mutant
Anaplastic astrocytoma WHO grade III IDH-wild type
Oligodendroglioma Oligodendroglioma WHO grade II
IDH-mutant and 1p19q-codeletion Oligodendroglioma WHO grade II
NOS
Anaplastic Oligodendroglioma WHO grade III IDH-mutant and 1p19q-codeletion
Anaplastic Oligodendroglioma WHO grade III NOS
Oligoastrocytoma NOS Anaplastic Oligoastrocytoma NOS
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Diffuse infiltrating glioma (2)
bull Glioblastomasbull Glioblastoma IDH-wild type
Giant cell glioblastoma
Gliosarcoma
Epithelioid glioblastoma
bull Glioblastoma IDH mutant
bull Glioblastoma NOS
bull Diffuse midline Glioma H3 K27M-mutant
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
IDH
Deregulation of IDH enzymatic activity is associated with human disease
Serena Tommasini-Ghelfi et al Sci Adv 20195eaaw4543
Copyright copy 2019 The Authors some rights reserved exclusive licensee American Association
for the Advancement of Science No claim to original US Government Works Distributed
under a Creative Commons Attribution NonCommercial License 40 (CC BY-NC)
IDH MUTATION VS IDH WILD TYPE
GLIOMA
Science 2008An integrated genomic analysis of human glioblastoma multiformeParsons DW1 Jones S Zhang X Lin JC Leary RJ Angenendt P Mankoo P Carter H Siu IM Gallia GL Olivi A McLendon R Rasheed BA Keir S Nikolskaya T Nikolsky Y Busam DA Tekleab H Diaz LA Jr Hartigan J Smith DR Strausberg RL Marie SK Shinjo SM Yan H Riggins GJ Bigner DD Karchin R Papadopoulos N Parmigiani G Vogelstein B Velculescu VE Kinzler KW
IDH1 amp IDH2
J NeurosurgTumor cell-specific chromosomal abnormality in the vascular endothelial cells of anaplastic oligodendrogliomaJiang H1 Zhang Z1 Ren X1 Zeng W1 Wang J2 Lin S1
1p19q co-deletion
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what else
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what to check
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
Key Points
bull Klasifikasi WHO terbaru untukTumor Saraf Pusat (2016)
bull Penegakan diagnosis klinis
bull Future direction
Klasifikasi WHO untukTumor Saraf Pusat
2016
Klasifikasi WHO untuk Tumor Otak 2016
19791988
19932007
2016
2007
2016
IDH
2007 2016
80rsquos 90rsquos
= BIOLOGY MOLECULAR ANALYSIS
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final
lengkap2 berdasar histologi3 grading 4 molecular
characteristicsActa Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final lengkap2 berdasar histologi3 grading 4 molecular characteristics
Contoh
Anaplastic astrocytoma WHO grade III IDH-wild type
1
2 3 4
( 2007 Anaplastic astrocytoma WHO grIII )
Diffuse infiltrating glioma
bull Diffuse astrocytoma Diffuse astrocytoma WHO grade II
IDH-mutantGemistocytic astrocytoma WHO grade II IDH-mutant
Diffuse astrocytoma WHO grade II IDH-wild type
Diffuse astrocytoma WHO grade II NOS
Anaplastic astrocytoma WHO grade III IDH-mutant
Anaplastic astrocytoma WHO grade III IDH-wild type
Oligodendroglioma Oligodendroglioma WHO grade II
IDH-mutant and 1p19q-codeletion Oligodendroglioma WHO grade II
NOS
Anaplastic Oligodendroglioma WHO grade III IDH-mutant and 1p19q-codeletion
Anaplastic Oligodendroglioma WHO grade III NOS
Oligoastrocytoma NOS Anaplastic Oligoastrocytoma NOS
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Diffuse infiltrating glioma (2)
bull Glioblastomasbull Glioblastoma IDH-wild type
Giant cell glioblastoma
Gliosarcoma
Epithelioid glioblastoma
bull Glioblastoma IDH mutant
bull Glioblastoma NOS
bull Diffuse midline Glioma H3 K27M-mutant
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
IDH
Deregulation of IDH enzymatic activity is associated with human disease
Serena Tommasini-Ghelfi et al Sci Adv 20195eaaw4543
Copyright copy 2019 The Authors some rights reserved exclusive licensee American Association
for the Advancement of Science No claim to original US Government Works Distributed
under a Creative Commons Attribution NonCommercial License 40 (CC BY-NC)
IDH MUTATION VS IDH WILD TYPE
GLIOMA
Science 2008An integrated genomic analysis of human glioblastoma multiformeParsons DW1 Jones S Zhang X Lin JC Leary RJ Angenendt P Mankoo P Carter H Siu IM Gallia GL Olivi A McLendon R Rasheed BA Keir S Nikolskaya T Nikolsky Y Busam DA Tekleab H Diaz LA Jr Hartigan J Smith DR Strausberg RL Marie SK Shinjo SM Yan H Riggins GJ Bigner DD Karchin R Papadopoulos N Parmigiani G Vogelstein B Velculescu VE Kinzler KW
IDH1 amp IDH2
J NeurosurgTumor cell-specific chromosomal abnormality in the vascular endothelial cells of anaplastic oligodendrogliomaJiang H1 Zhang Z1 Ren X1 Zeng W1 Wang J2 Lin S1
1p19q co-deletion
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what else
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what to check
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
Klasifikasi WHO untukTumor Saraf Pusat
2016
Klasifikasi WHO untuk Tumor Otak 2016
19791988
19932007
2016
2007
2016
IDH
2007 2016
80rsquos 90rsquos
= BIOLOGY MOLECULAR ANALYSIS
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final
lengkap2 berdasar histologi3 grading 4 molecular
characteristicsActa Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final lengkap2 berdasar histologi3 grading 4 molecular characteristics
Contoh
Anaplastic astrocytoma WHO grade III IDH-wild type
1
2 3 4
( 2007 Anaplastic astrocytoma WHO grIII )
Diffuse infiltrating glioma
bull Diffuse astrocytoma Diffuse astrocytoma WHO grade II
IDH-mutantGemistocytic astrocytoma WHO grade II IDH-mutant
Diffuse astrocytoma WHO grade II IDH-wild type
Diffuse astrocytoma WHO grade II NOS
Anaplastic astrocytoma WHO grade III IDH-mutant
Anaplastic astrocytoma WHO grade III IDH-wild type
Oligodendroglioma Oligodendroglioma WHO grade II
IDH-mutant and 1p19q-codeletion Oligodendroglioma WHO grade II
NOS
Anaplastic Oligodendroglioma WHO grade III IDH-mutant and 1p19q-codeletion
Anaplastic Oligodendroglioma WHO grade III NOS
Oligoastrocytoma NOS Anaplastic Oligoastrocytoma NOS
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Diffuse infiltrating glioma (2)
bull Glioblastomasbull Glioblastoma IDH-wild type
Giant cell glioblastoma
Gliosarcoma
Epithelioid glioblastoma
bull Glioblastoma IDH mutant
bull Glioblastoma NOS
bull Diffuse midline Glioma H3 K27M-mutant
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
IDH
Deregulation of IDH enzymatic activity is associated with human disease
Serena Tommasini-Ghelfi et al Sci Adv 20195eaaw4543
Copyright copy 2019 The Authors some rights reserved exclusive licensee American Association
for the Advancement of Science No claim to original US Government Works Distributed
under a Creative Commons Attribution NonCommercial License 40 (CC BY-NC)
IDH MUTATION VS IDH WILD TYPE
GLIOMA
Science 2008An integrated genomic analysis of human glioblastoma multiformeParsons DW1 Jones S Zhang X Lin JC Leary RJ Angenendt P Mankoo P Carter H Siu IM Gallia GL Olivi A McLendon R Rasheed BA Keir S Nikolskaya T Nikolsky Y Busam DA Tekleab H Diaz LA Jr Hartigan J Smith DR Strausberg RL Marie SK Shinjo SM Yan H Riggins GJ Bigner DD Karchin R Papadopoulos N Parmigiani G Vogelstein B Velculescu VE Kinzler KW
IDH1 amp IDH2
J NeurosurgTumor cell-specific chromosomal abnormality in the vascular endothelial cells of anaplastic oligodendrogliomaJiang H1 Zhang Z1 Ren X1 Zeng W1 Wang J2 Lin S1
1p19q co-deletion
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what else
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what to check
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
Klasifikasi WHO untuk Tumor Otak 2016
19791988
19932007
2016
2007
2016
IDH
2007 2016
80rsquos 90rsquos
= BIOLOGY MOLECULAR ANALYSIS
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final
lengkap2 berdasar histologi3 grading 4 molecular
characteristicsActa Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final lengkap2 berdasar histologi3 grading 4 molecular characteristics
Contoh
Anaplastic astrocytoma WHO grade III IDH-wild type
1
2 3 4
( 2007 Anaplastic astrocytoma WHO grIII )
Diffuse infiltrating glioma
bull Diffuse astrocytoma Diffuse astrocytoma WHO grade II
IDH-mutantGemistocytic astrocytoma WHO grade II IDH-mutant
Diffuse astrocytoma WHO grade II IDH-wild type
Diffuse astrocytoma WHO grade II NOS
Anaplastic astrocytoma WHO grade III IDH-mutant
Anaplastic astrocytoma WHO grade III IDH-wild type
Oligodendroglioma Oligodendroglioma WHO grade II
IDH-mutant and 1p19q-codeletion Oligodendroglioma WHO grade II
NOS
Anaplastic Oligodendroglioma WHO grade III IDH-mutant and 1p19q-codeletion
Anaplastic Oligodendroglioma WHO grade III NOS
Oligoastrocytoma NOS Anaplastic Oligoastrocytoma NOS
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Diffuse infiltrating glioma (2)
bull Glioblastomasbull Glioblastoma IDH-wild type
Giant cell glioblastoma
Gliosarcoma
Epithelioid glioblastoma
bull Glioblastoma IDH mutant
bull Glioblastoma NOS
bull Diffuse midline Glioma H3 K27M-mutant
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
IDH
Deregulation of IDH enzymatic activity is associated with human disease
Serena Tommasini-Ghelfi et al Sci Adv 20195eaaw4543
Copyright copy 2019 The Authors some rights reserved exclusive licensee American Association
for the Advancement of Science No claim to original US Government Works Distributed
under a Creative Commons Attribution NonCommercial License 40 (CC BY-NC)
IDH MUTATION VS IDH WILD TYPE
GLIOMA
Science 2008An integrated genomic analysis of human glioblastoma multiformeParsons DW1 Jones S Zhang X Lin JC Leary RJ Angenendt P Mankoo P Carter H Siu IM Gallia GL Olivi A McLendon R Rasheed BA Keir S Nikolskaya T Nikolsky Y Busam DA Tekleab H Diaz LA Jr Hartigan J Smith DR Strausberg RL Marie SK Shinjo SM Yan H Riggins GJ Bigner DD Karchin R Papadopoulos N Parmigiani G Vogelstein B Velculescu VE Kinzler KW
IDH1 amp IDH2
J NeurosurgTumor cell-specific chromosomal abnormality in the vascular endothelial cells of anaplastic oligodendrogliomaJiang H1 Zhang Z1 Ren X1 Zeng W1 Wang J2 Lin S1
1p19q co-deletion
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what else
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what to check
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
2007
2016
IDH
2007 2016
80rsquos 90rsquos
= BIOLOGY MOLECULAR ANALYSIS
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final
lengkap2 berdasar histologi3 grading 4 molecular
characteristicsActa Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final lengkap2 berdasar histologi3 grading 4 molecular characteristics
Contoh
Anaplastic astrocytoma WHO grade III IDH-wild type
1
2 3 4
( 2007 Anaplastic astrocytoma WHO grIII )
Diffuse infiltrating glioma
bull Diffuse astrocytoma Diffuse astrocytoma WHO grade II
IDH-mutantGemistocytic astrocytoma WHO grade II IDH-mutant
Diffuse astrocytoma WHO grade II IDH-wild type
Diffuse astrocytoma WHO grade II NOS
Anaplastic astrocytoma WHO grade III IDH-mutant
Anaplastic astrocytoma WHO grade III IDH-wild type
Oligodendroglioma Oligodendroglioma WHO grade II
IDH-mutant and 1p19q-codeletion Oligodendroglioma WHO grade II
NOS
Anaplastic Oligodendroglioma WHO grade III IDH-mutant and 1p19q-codeletion
Anaplastic Oligodendroglioma WHO grade III NOS
Oligoastrocytoma NOS Anaplastic Oligoastrocytoma NOS
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Diffuse infiltrating glioma (2)
bull Glioblastomasbull Glioblastoma IDH-wild type
Giant cell glioblastoma
Gliosarcoma
Epithelioid glioblastoma
bull Glioblastoma IDH mutant
bull Glioblastoma NOS
bull Diffuse midline Glioma H3 K27M-mutant
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
IDH
Deregulation of IDH enzymatic activity is associated with human disease
Serena Tommasini-Ghelfi et al Sci Adv 20195eaaw4543
Copyright copy 2019 The Authors some rights reserved exclusive licensee American Association
for the Advancement of Science No claim to original US Government Works Distributed
under a Creative Commons Attribution NonCommercial License 40 (CC BY-NC)
IDH MUTATION VS IDH WILD TYPE
GLIOMA
Science 2008An integrated genomic analysis of human glioblastoma multiformeParsons DW1 Jones S Zhang X Lin JC Leary RJ Angenendt P Mankoo P Carter H Siu IM Gallia GL Olivi A McLendon R Rasheed BA Keir S Nikolskaya T Nikolsky Y Busam DA Tekleab H Diaz LA Jr Hartigan J Smith DR Strausberg RL Marie SK Shinjo SM Yan H Riggins GJ Bigner DD Karchin R Papadopoulos N Parmigiani G Vogelstein B Velculescu VE Kinzler KW
IDH1 amp IDH2
J NeurosurgTumor cell-specific chromosomal abnormality in the vascular endothelial cells of anaplastic oligodendrogliomaJiang H1 Zhang Z1 Ren X1 Zeng W1 Wang J2 Lin S1
1p19q co-deletion
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what else
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what to check
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
2007 2016
80rsquos 90rsquos
= BIOLOGY MOLECULAR ANALYSIS
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final
lengkap2 berdasar histologi3 grading 4 molecular
characteristicsActa Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final lengkap2 berdasar histologi3 grading 4 molecular characteristics
Contoh
Anaplastic astrocytoma WHO grade III IDH-wild type
1
2 3 4
( 2007 Anaplastic astrocytoma WHO grIII )
Diffuse infiltrating glioma
bull Diffuse astrocytoma Diffuse astrocytoma WHO grade II
IDH-mutantGemistocytic astrocytoma WHO grade II IDH-mutant
Diffuse astrocytoma WHO grade II IDH-wild type
Diffuse astrocytoma WHO grade II NOS
Anaplastic astrocytoma WHO grade III IDH-mutant
Anaplastic astrocytoma WHO grade III IDH-wild type
Oligodendroglioma Oligodendroglioma WHO grade II
IDH-mutant and 1p19q-codeletion Oligodendroglioma WHO grade II
NOS
Anaplastic Oligodendroglioma WHO grade III IDH-mutant and 1p19q-codeletion
Anaplastic Oligodendroglioma WHO grade III NOS
Oligoastrocytoma NOS Anaplastic Oligoastrocytoma NOS
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Diffuse infiltrating glioma (2)
bull Glioblastomasbull Glioblastoma IDH-wild type
Giant cell glioblastoma
Gliosarcoma
Epithelioid glioblastoma
bull Glioblastoma IDH mutant
bull Glioblastoma NOS
bull Diffuse midline Glioma H3 K27M-mutant
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
IDH
Deregulation of IDH enzymatic activity is associated with human disease
Serena Tommasini-Ghelfi et al Sci Adv 20195eaaw4543
Copyright copy 2019 The Authors some rights reserved exclusive licensee American Association
for the Advancement of Science No claim to original US Government Works Distributed
under a Creative Commons Attribution NonCommercial License 40 (CC BY-NC)
IDH MUTATION VS IDH WILD TYPE
GLIOMA
Science 2008An integrated genomic analysis of human glioblastoma multiformeParsons DW1 Jones S Zhang X Lin JC Leary RJ Angenendt P Mankoo P Carter H Siu IM Gallia GL Olivi A McLendon R Rasheed BA Keir S Nikolskaya T Nikolsky Y Busam DA Tekleab H Diaz LA Jr Hartigan J Smith DR Strausberg RL Marie SK Shinjo SM Yan H Riggins GJ Bigner DD Karchin R Papadopoulos N Parmigiani G Vogelstein B Velculescu VE Kinzler KW
IDH1 amp IDH2
J NeurosurgTumor cell-specific chromosomal abnormality in the vascular endothelial cells of anaplastic oligodendrogliomaJiang H1 Zhang Z1 Ren X1 Zeng W1 Wang J2 Lin S1
1p19q co-deletion
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what else
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what to check
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final
lengkap2 berdasar histologi3 grading 4 molecular
characteristicsActa Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final lengkap2 berdasar histologi3 grading 4 molecular characteristics
Contoh
Anaplastic astrocytoma WHO grade III IDH-wild type
1
2 3 4
( 2007 Anaplastic astrocytoma WHO grIII )
Diffuse infiltrating glioma
bull Diffuse astrocytoma Diffuse astrocytoma WHO grade II
IDH-mutantGemistocytic astrocytoma WHO grade II IDH-mutant
Diffuse astrocytoma WHO grade II IDH-wild type
Diffuse astrocytoma WHO grade II NOS
Anaplastic astrocytoma WHO grade III IDH-mutant
Anaplastic astrocytoma WHO grade III IDH-wild type
Oligodendroglioma Oligodendroglioma WHO grade II
IDH-mutant and 1p19q-codeletion Oligodendroglioma WHO grade II
NOS
Anaplastic Oligodendroglioma WHO grade III IDH-mutant and 1p19q-codeletion
Anaplastic Oligodendroglioma WHO grade III NOS
Oligoastrocytoma NOS Anaplastic Oligoastrocytoma NOS
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Diffuse infiltrating glioma (2)
bull Glioblastomasbull Glioblastoma IDH-wild type
Giant cell glioblastoma
Gliosarcoma
Epithelioid glioblastoma
bull Glioblastoma IDH mutant
bull Glioblastoma NOS
bull Diffuse midline Glioma H3 K27M-mutant
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
IDH
Deregulation of IDH enzymatic activity is associated with human disease
Serena Tommasini-Ghelfi et al Sci Adv 20195eaaw4543
Copyright copy 2019 The Authors some rights reserved exclusive licensee American Association
for the Advancement of Science No claim to original US Government Works Distributed
under a Creative Commons Attribution NonCommercial License 40 (CC BY-NC)
IDH MUTATION VS IDH WILD TYPE
GLIOMA
Science 2008An integrated genomic analysis of human glioblastoma multiformeParsons DW1 Jones S Zhang X Lin JC Leary RJ Angenendt P Mankoo P Carter H Siu IM Gallia GL Olivi A McLendon R Rasheed BA Keir S Nikolskaya T Nikolsky Y Busam DA Tekleab H Diaz LA Jr Hartigan J Smith DR Strausberg RL Marie SK Shinjo SM Yan H Riggins GJ Bigner DD Karchin R Papadopoulos N Parmigiani G Vogelstein B Velculescu VE Kinzler KW
IDH1 amp IDH2
J NeurosurgTumor cell-specific chromosomal abnormality in the vascular endothelial cells of anaplastic oligodendrogliomaJiang H1 Zhang Z1 Ren X1 Zeng W1 Wang J2 Lin S1
1p19q co-deletion
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what else
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what to check
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
Nomenklatur
Metode penamaan dengan Layered diagnosis1 diagnosis final lengkap2 berdasar histologi3 grading 4 molecular characteristics
Contoh
Anaplastic astrocytoma WHO grade III IDH-wild type
1
2 3 4
( 2007 Anaplastic astrocytoma WHO grIII )
Diffuse infiltrating glioma
bull Diffuse astrocytoma Diffuse astrocytoma WHO grade II
IDH-mutantGemistocytic astrocytoma WHO grade II IDH-mutant
Diffuse astrocytoma WHO grade II IDH-wild type
Diffuse astrocytoma WHO grade II NOS
Anaplastic astrocytoma WHO grade III IDH-mutant
Anaplastic astrocytoma WHO grade III IDH-wild type
Oligodendroglioma Oligodendroglioma WHO grade II
IDH-mutant and 1p19q-codeletion Oligodendroglioma WHO grade II
NOS
Anaplastic Oligodendroglioma WHO grade III IDH-mutant and 1p19q-codeletion
Anaplastic Oligodendroglioma WHO grade III NOS
Oligoastrocytoma NOS Anaplastic Oligoastrocytoma NOS
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Diffuse infiltrating glioma (2)
bull Glioblastomasbull Glioblastoma IDH-wild type
Giant cell glioblastoma
Gliosarcoma
Epithelioid glioblastoma
bull Glioblastoma IDH mutant
bull Glioblastoma NOS
bull Diffuse midline Glioma H3 K27M-mutant
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
IDH
Deregulation of IDH enzymatic activity is associated with human disease
Serena Tommasini-Ghelfi et al Sci Adv 20195eaaw4543
Copyright copy 2019 The Authors some rights reserved exclusive licensee American Association
for the Advancement of Science No claim to original US Government Works Distributed
under a Creative Commons Attribution NonCommercial License 40 (CC BY-NC)
IDH MUTATION VS IDH WILD TYPE
GLIOMA
Science 2008An integrated genomic analysis of human glioblastoma multiformeParsons DW1 Jones S Zhang X Lin JC Leary RJ Angenendt P Mankoo P Carter H Siu IM Gallia GL Olivi A McLendon R Rasheed BA Keir S Nikolskaya T Nikolsky Y Busam DA Tekleab H Diaz LA Jr Hartigan J Smith DR Strausberg RL Marie SK Shinjo SM Yan H Riggins GJ Bigner DD Karchin R Papadopoulos N Parmigiani G Vogelstein B Velculescu VE Kinzler KW
IDH1 amp IDH2
J NeurosurgTumor cell-specific chromosomal abnormality in the vascular endothelial cells of anaplastic oligodendrogliomaJiang H1 Zhang Z1 Ren X1 Zeng W1 Wang J2 Lin S1
1p19q co-deletion
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what else
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what to check
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
Diffuse infiltrating glioma
bull Diffuse astrocytoma Diffuse astrocytoma WHO grade II
IDH-mutantGemistocytic astrocytoma WHO grade II IDH-mutant
Diffuse astrocytoma WHO grade II IDH-wild type
Diffuse astrocytoma WHO grade II NOS
Anaplastic astrocytoma WHO grade III IDH-mutant
Anaplastic astrocytoma WHO grade III IDH-wild type
Oligodendroglioma Oligodendroglioma WHO grade II
IDH-mutant and 1p19q-codeletion Oligodendroglioma WHO grade II
NOS
Anaplastic Oligodendroglioma WHO grade III IDH-mutant and 1p19q-codeletion
Anaplastic Oligodendroglioma WHO grade III NOS
Oligoastrocytoma NOS Anaplastic Oligoastrocytoma NOS
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
Diffuse infiltrating glioma (2)
bull Glioblastomasbull Glioblastoma IDH-wild type
Giant cell glioblastoma
Gliosarcoma
Epithelioid glioblastoma
bull Glioblastoma IDH mutant
bull Glioblastoma NOS
bull Diffuse midline Glioma H3 K27M-mutant
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
IDH
Deregulation of IDH enzymatic activity is associated with human disease
Serena Tommasini-Ghelfi et al Sci Adv 20195eaaw4543
Copyright copy 2019 The Authors some rights reserved exclusive licensee American Association
for the Advancement of Science No claim to original US Government Works Distributed
under a Creative Commons Attribution NonCommercial License 40 (CC BY-NC)
IDH MUTATION VS IDH WILD TYPE
GLIOMA
Science 2008An integrated genomic analysis of human glioblastoma multiformeParsons DW1 Jones S Zhang X Lin JC Leary RJ Angenendt P Mankoo P Carter H Siu IM Gallia GL Olivi A McLendon R Rasheed BA Keir S Nikolskaya T Nikolsky Y Busam DA Tekleab H Diaz LA Jr Hartigan J Smith DR Strausberg RL Marie SK Shinjo SM Yan H Riggins GJ Bigner DD Karchin R Papadopoulos N Parmigiani G Vogelstein B Velculescu VE Kinzler KW
IDH1 amp IDH2
J NeurosurgTumor cell-specific chromosomal abnormality in the vascular endothelial cells of anaplastic oligodendrogliomaJiang H1 Zhang Z1 Ren X1 Zeng W1 Wang J2 Lin S1
1p19q co-deletion
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what else
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what to check
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
Diffuse infiltrating glioma (2)
bull Glioblastomasbull Glioblastoma IDH-wild type
Giant cell glioblastoma
Gliosarcoma
Epithelioid glioblastoma
bull Glioblastoma IDH mutant
bull Glioblastoma NOS
bull Diffuse midline Glioma H3 K27M-mutant
Acta Neurochir (Wien) 2017 The new WHO 2016 classification of brain tumors-what neurosurgeons need to knowBanan R1 Hartmann C2
IDH
Deregulation of IDH enzymatic activity is associated with human disease
Serena Tommasini-Ghelfi et al Sci Adv 20195eaaw4543
Copyright copy 2019 The Authors some rights reserved exclusive licensee American Association
for the Advancement of Science No claim to original US Government Works Distributed
under a Creative Commons Attribution NonCommercial License 40 (CC BY-NC)
IDH MUTATION VS IDH WILD TYPE
GLIOMA
Science 2008An integrated genomic analysis of human glioblastoma multiformeParsons DW1 Jones S Zhang X Lin JC Leary RJ Angenendt P Mankoo P Carter H Siu IM Gallia GL Olivi A McLendon R Rasheed BA Keir S Nikolskaya T Nikolsky Y Busam DA Tekleab H Diaz LA Jr Hartigan J Smith DR Strausberg RL Marie SK Shinjo SM Yan H Riggins GJ Bigner DD Karchin R Papadopoulos N Parmigiani G Vogelstein B Velculescu VE Kinzler KW
IDH1 amp IDH2
J NeurosurgTumor cell-specific chromosomal abnormality in the vascular endothelial cells of anaplastic oligodendrogliomaJiang H1 Zhang Z1 Ren X1 Zeng W1 Wang J2 Lin S1
1p19q co-deletion
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what else
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what to check
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
IDH
Deregulation of IDH enzymatic activity is associated with human disease
Serena Tommasini-Ghelfi et al Sci Adv 20195eaaw4543
Copyright copy 2019 The Authors some rights reserved exclusive licensee American Association
for the Advancement of Science No claim to original US Government Works Distributed
under a Creative Commons Attribution NonCommercial License 40 (CC BY-NC)
IDH MUTATION VS IDH WILD TYPE
GLIOMA
Science 2008An integrated genomic analysis of human glioblastoma multiformeParsons DW1 Jones S Zhang X Lin JC Leary RJ Angenendt P Mankoo P Carter H Siu IM Gallia GL Olivi A McLendon R Rasheed BA Keir S Nikolskaya T Nikolsky Y Busam DA Tekleab H Diaz LA Jr Hartigan J Smith DR Strausberg RL Marie SK Shinjo SM Yan H Riggins GJ Bigner DD Karchin R Papadopoulos N Parmigiani G Vogelstein B Velculescu VE Kinzler KW
IDH1 amp IDH2
J NeurosurgTumor cell-specific chromosomal abnormality in the vascular endothelial cells of anaplastic oligodendrogliomaJiang H1 Zhang Z1 Ren X1 Zeng W1 Wang J2 Lin S1
1p19q co-deletion
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what else
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what to check
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
Deregulation of IDH enzymatic activity is associated with human disease
Serena Tommasini-Ghelfi et al Sci Adv 20195eaaw4543
Copyright copy 2019 The Authors some rights reserved exclusive licensee American Association
for the Advancement of Science No claim to original US Government Works Distributed
under a Creative Commons Attribution NonCommercial License 40 (CC BY-NC)
IDH MUTATION VS IDH WILD TYPE
GLIOMA
Science 2008An integrated genomic analysis of human glioblastoma multiformeParsons DW1 Jones S Zhang X Lin JC Leary RJ Angenendt P Mankoo P Carter H Siu IM Gallia GL Olivi A McLendon R Rasheed BA Keir S Nikolskaya T Nikolsky Y Busam DA Tekleab H Diaz LA Jr Hartigan J Smith DR Strausberg RL Marie SK Shinjo SM Yan H Riggins GJ Bigner DD Karchin R Papadopoulos N Parmigiani G Vogelstein B Velculescu VE Kinzler KW
IDH1 amp IDH2
J NeurosurgTumor cell-specific chromosomal abnormality in the vascular endothelial cells of anaplastic oligodendrogliomaJiang H1 Zhang Z1 Ren X1 Zeng W1 Wang J2 Lin S1
1p19q co-deletion
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what else
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what to check
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
IDH MUTATION VS IDH WILD TYPE
GLIOMA
Science 2008An integrated genomic analysis of human glioblastoma multiformeParsons DW1 Jones S Zhang X Lin JC Leary RJ Angenendt P Mankoo P Carter H Siu IM Gallia GL Olivi A McLendon R Rasheed BA Keir S Nikolskaya T Nikolsky Y Busam DA Tekleab H Diaz LA Jr Hartigan J Smith DR Strausberg RL Marie SK Shinjo SM Yan H Riggins GJ Bigner DD Karchin R Papadopoulos N Parmigiani G Vogelstein B Velculescu VE Kinzler KW
IDH1 amp IDH2
J NeurosurgTumor cell-specific chromosomal abnormality in the vascular endothelial cells of anaplastic oligodendrogliomaJiang H1 Zhang Z1 Ren X1 Zeng W1 Wang J2 Lin S1
1p19q co-deletion
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what else
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what to check
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
Science 2008An integrated genomic analysis of human glioblastoma multiformeParsons DW1 Jones S Zhang X Lin JC Leary RJ Angenendt P Mankoo P Carter H Siu IM Gallia GL Olivi A McLendon R Rasheed BA Keir S Nikolskaya T Nikolsky Y Busam DA Tekleab H Diaz LA Jr Hartigan J Smith DR Strausberg RL Marie SK Shinjo SM Yan H Riggins GJ Bigner DD Karchin R Papadopoulos N Parmigiani G Vogelstein B Velculescu VE Kinzler KW
IDH1 amp IDH2
J NeurosurgTumor cell-specific chromosomal abnormality in the vascular endothelial cells of anaplastic oligodendrogliomaJiang H1 Zhang Z1 Ren X1 Zeng W1 Wang J2 Lin S1
1p19q co-deletion
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what else
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what to check
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
J NeurosurgTumor cell-specific chromosomal abnormality in the vascular endothelial cells of anaplastic oligodendrogliomaJiang H1 Zhang Z1 Ren X1 Zeng W1 Wang J2 Lin S1
1p19q co-deletion
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what else
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what to check
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what else
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what to check
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
Neuro Oncol 2019
The medical necessity of advanced molecular testing in the diagnosis and treatment of brain tumor patients
Horbinski C12 Ligon KL34 Brastianos P5 Huse JT67 Venere M8 Chang S9 Buckner J10 Cloughesy T11 Jenkins
RB12 Giannini C12 Stupp R213 Nabors LB14 Wen PY1516 Aldape KJ17 Lukas RV13 Galanis E10 Eberhart
CG131819 Brat DJ1 Sarkaria JN20
what to check
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
HOW TO
PREDICT
PROGNOSIS
Nature 2018 Breaking down the epidemiology of brain cancer
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
HOW TO
PREDICT
PROGNOSIS
Ann Transl Med 2019
Clinical prognostic value of isocitrate dehydrogenase mutation O-6-methylguanine-DNA
methyltransferase promoter methylation and 1p19q co-deletion in glioma patients Chen X12 Yan Y12 Zhou J3 Huo L4 Qian L12 Zeng S12 Li Z5 Wei J12 Xu Z3 Gong Z12
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
Take home message
Revisi WHO 2016 untuk glioma
1 Status mutasi IDH1 dan IDH22 Kodelesi 1p19q
3 Perubahan pohon klasifikasi4 Penghapusan beberap diagnosis
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
Take home message
bull WHO tidak memberi standar metode pemeriksaanuntuk penegakan status molekulerKeuntungan
Memberi kesempatan semua pusat studi untuk mencarimetode yang paling ideal
Tata laksana pasien bisa tetap berjalan dengan diagnosis NOS
Kerugian
Terjadi bias data
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
Penegakan
diagnosis
klinis
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
Penegakan diagnosis
a MRI b-c-d HE Glioblastoma with Primitive neural componente GFAP f synaptophysin (IHC) confirm glial marker expressiong IDH1 R132H mutant (IHC) secondary GBMh FISH (fluorescence in situ hybridization) MYCN gene amplification (confirm primitive foci gene)
Contoh kasus 1 GBM with PNC
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
Penegakan diagnosis
a-b autopsyc-d HE infiltrasi leptomening dan gambaran sel oligodenroglial tumore OLIG2 (IHC) f synaptophysin confirm oligodendroglial componentg-h FISH 1p 19q labelling amp BRAF labelling (confirm oligodendroglial)
Contoh kasus 2 Diffuse leptomeningeal glioneuronal tumors (DLGNT)
Acta Neuropathol 2016The 2016 World Health Organization Classification of Tumors of the Central Nervous System a summaryLouis DN1 Perry A2 Reifenberger G34 von Deimling A45 Figarella-Branger D6 Cavenee WK7 Ohgaki H8 Wiestler OD9 Kleihues P10 Ellison DW11
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
Operasi bedah
radiasi
temozolamide
RESISTEN EFEKTIF
1 tahun 5 tahun2 tahun 5 bulan
CONVENTIONAL
THERAPY
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
ID MUTANT IDH WILD TYPE
1p19q codeletion TP53 mutation
MGMT UNMETILATED EGFR Amplification
(Ex) ANAPLASTIC ASTROCYTOMA WHO GRADE III
SURGERY GOAL
ldquoPERSONALIZED THERAPYrdquo
DETERMINED PROGNOSIS
BIOMOL
ANALYSIS
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
Take home message
INDONESIA
Diagnosis
Terapi
Prognosis
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
FUTURE
DIRECTION
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
Testing Method
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
FUTURE GLIOMA THERAPY
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
Proposed intraoperative workflow for genotype-targeted therapy of glioma
Ganesh M Shankar et al PNAS 201811536E8388-E8394
copy2018 by National Academy of Sciences
FUTURE GLIOMA THERAPY
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
FUTURE DIRECTION
prognosis
diagnosis
therapy
databaseNeuroscience
Neuroimaging
Neurophatology
Neurobehaviour
Etc
Neurologist
Neurosurgeon
Radiologist
Oncologist
Bioengineer
Etc
Registry
Research
Bioinformatics
Insurance system
governance
Education
Etc
= Biomolecular analysis
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
FUTURE DIRECTION
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
TAKE HOME MESSAGE
bull Umum
bull Pasien dan keluarga
bull Nakes
bull PPDS
bull Dokter spesialis
bull Lintas bidang
KOLABORASI
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
SUMMARY
bull Standar diagnosis tumor saraf pusat = ldquoTRANSISIrdquo
bull Tata laksana pada tumor saraf pusat belumsepenuhnya berubah saat ini
modifikasi terapi konvensional
targeted therapy
personalized therapy
bull Tantangan untuk klinisi
di masa depan
