introduction - tumor otak, kanker otak, gejala tumor otak

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PowerPoint PresentationPresenter: Asadullah Advisor: Dr. dr. Joni Wahyuhadi, SpBS (K) Dr. dr. Rahadian Indarto S. SpBS (K) dr. Irwan Barlian I. H, SpBS (K) 0
Introduction
FK UNAIR – RSUD dr Soetomo
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Introduction
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20% dari seluruh kasus tumor susunan saraf pusat pada anak
Pertama kali diperkenalkan oleh Harvey Cushing dan Percival Bailey pada tahun 1925
Berpotensi untuk menyebar melalui celah sub arachnoid dan bahkan pada beberapa kasus
dapat bermetastasis keluar dari susunan saraf pusat
Epidemiologi
FK UNAIR – RSUD dr Soetomo
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Sales
• Central Brain Tumor Registry (CBTRUS) high grade glioma (secara total) > medulloblastoma
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
FK UNAIR – RSUD dr Soetomo
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History
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• Cushing mendeskripsikan medulloblastoma sebagai tumor yang tumbuh dari vermis cerebellum dan dapat bermetastasis ke lokasi yang jauh serta lebih cenderung terjadi pada laki-laki usia muda
History
• Based on histological similarity between medulloblastomas and other small round blue cell tumors arising in areas outside of the posterior fossa, it was proposed that these tumors be classified together under the umbrella group of primitive neuroectodermal tumors (PNETs)
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
FK UNAIR – RSUD dr Soetomo
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History
• We show further that the clinical outcome of children with medulloblastomas is highly predictable on the basis of the gene expression profiles of their tumours at diagnosis
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
FK UNAIR – RSUD dr Soetomo
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Etiology
• Non-fresh peaches and similar fruits (OR = 0.5, 95% CI: 0.3, 0.8), non- chocolate candy (OR = 1.7, 95% CI: 1.0, 3.0), french fries (OR = 2.4, 95% CI: 1.2, 4.9) and chili peppers (OR = 1.8, 95% CI: 1.0, 3.0) were associated with medulloblastoma/PNET.
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
FK UNAIR – RSUD dr Soetomo
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Etiology
• Neurotropic JC virus (JCV) is able to induce cerebellar neoplasms in rodents that exhibit a phenotype similar to that of human medulloblastomas
• By using PCR techniques we demonstrate that 11 of 23 samples of tumor tissue contain DNA sequences corresponding to three different regions of the JCV genome
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
FK UNAIR – RSUD dr Soetomo
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Etiology
• HCMV encodes proteins that provide immune evasion strategies and promote oncogenic transformation and oncomodulation
• HCMV induces COX-2 expression; STAT3 phosphorylation; production of PGE2, vascular endothelial growth factor, and IL-6; and tumor formation in vivo
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
FK UNAIR – RSUD dr Soetomo
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Etiology
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Histology
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• Klasik medulloblastoma (70%)
Sel pada tumor tampak sangat padat dengan nukleus berbentuk bulat atau oval dengan gambaran hiperkromatik
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
FK UNAIR – RSUD dr Soetomo
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Histology
• Tumor memiliki gambaran retikulen-free nodul dengan densitas lebih rendah pada daerah internodular. Desmoplasia terjadi pada daerah internodular.
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
FK UNAIR – RSUD dr Soetomo
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Histology
• Large-cell anaplastic (10%)
• Sel yang berukuran besar dengan nucleus bulat dan prominen serta proporsi sitoplasma yang lebih banyak dari jenis klasik
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
FK UNAIR – RSUD dr Soetomo
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Patofisiologi
• Cusing melihat adanya sel neural dan glia pada medulloblastoma yang mengesankan bahwa medulloblastoma berasal dari sel yang lebih primitif yaitu embryonic neuroepithelial cell yang kemudian dinamakan “medulloblast”
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
FK UNAIR – RSUD dr Soetomo
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Patofisiologi
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Patofisiologi
• Cerebellum berasal dari beberapa regio termasuk bagian atas rhombic lip dan zona ventricular di sekeliling ventrikel empat yang berkembang selama fase embrio dan mencapai maturase pada beberapa bulan setelah kelahiran
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
FK UNAIR – RSUD dr Soetomo
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Patofisiologi
• Transcriptional profiling studies of medulloblastoma cohorts from several research groups around the globe have suggested the existence of multiple distinct molecular subgroups that differ in their demographics, transcriptomes, somatic genetic events, and clinical outcomes
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
FK UNAIR – RSUD dr Soetomo
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FK UNAIR – RSUD dr Soetomo
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Sonic Hedgeog
• Gli1 dan Gli2 berperan penting pada pembentukan dan regulasi pembelahan sel pada cancer
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
FK UNAIR – RSUD dr Soetomo
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Wingless
• Adanya TCF menyebabkan aktivasi transkripsi gen c-myc dan Cylin D1 yang berperan dalam proliferasi gen dan bersifat proto-oncogenes
22 Ilmiah Divisi Neuro-Onkologi
Patofisiologi
• Aktivasi berlebihan pada kedua jalur diatas baik Shh dan Wnt dapat memicu terjadinya medulloblastoma akibat terbentuknya proto oncogene dan kegagalan sel untuk keluar dari kondisi proliferative dan masuk pada proses deferensiasi
23 Ilmiah Divisi Neuro-Onkologi
Classification (Histology)
• Their response to treatment is highly variable
• Histological classification may have limited prognostic value.
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
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presence of metastatic disease
Other
Cure rates of average and high-risk patients are 85 and 70%
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
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Anamnesis
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Work-up
Imaging
Sitologi
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Imaging
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week post op
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• With the use of either CSF cytology or spinal MRI alone, LMD would be missed in up to 14% to 18% of patients with medulloblastoma or PNET
• 3:1 male/female ratio
• Bone was the most frequent site of metastases in adults (77%) and children (78%) Followed by lymph nodes (33%) in both children and adults. Lung metastases were more common in adults (17%), but liver metastases occurred more frequently in children (15%)
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
FK UNAIR – RSUD dr Soetomo
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High Risk (under 3 year)
Screening (ex. Bone Scan)
Management
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Surgery
RadiotherapyChemoterapy
Targetted ??
History
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
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• Prognosis pasien dengan medulloblastoma tetap buruk sampai diperkenalkannya radiasi kraniospinal oleh Paterson dan Farr pada tahun 1953 (survival rate 3th mencapai 65% )
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
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History
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Gangguan neurokognitif
Disfungsi endokrin
Tumor sekunder
Reduction in the IQ score as high as 40 points
Endocrine deficits occurred in 45%
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
FK UNAIR – RSUD dr Soetomo
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History
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Surgery
KemoterapiRadioterapi
History
• 5-year overall survival was 85% (95% CI 75-94) in patients in the average-risk group and 70% (54-84) in those in the high-risk group (p=0.04); 5-year event-free survival was 83% (73-93) and 70% (55-85)
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
FK UNAIR – RSUD dr Soetomo
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History
• 5-year overall survival ± SE and progression-free survival ± SE for M+ patients treated at the RP2D on regimen A was 82% ± 9% and 71% ± 11% versus 68% ± 10% and 59% ± 10% on regimen B (P = .36)
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
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History
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Surgery
Kemoterapi
Radioterapi
Targeted
History
• Despite the body of literature describing the molecular subgroups, these findings have yet to translate directly to the clinical realm. Standard of care treatment remains maximal up front surgical resection followed by radiation and chemotherapy.
Ilmiah Divisi Neuro-Onkologi Departemen Bedah Saraf
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Surgery
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High Risk
Surgical approach
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Transcortical
Cerebellum
Transvermian
Telovelar
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• Splitting the inferior vermis on the sub-occipital surface. The incision extends a variable distance through the uvula, pyramid, tuber, and folium of the vermis, depending on the location and size of the lesion
• Retracting the two halves of the lower vermis laterally, then opening the telachoroidea and the inferior medullary velum, exposing the full length of the floor from the aqueduct to the obex
Telovelar
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• Examine the access to the fourth ventricle achieved by opening the tela choroidea and inferior medullary velum without incising or removing part of the cerebellum.
Telovelar
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• The medullotonsillar space of the cerebellomedullary fissure and the uvulotonsillar space are sharply dissected to release the tonsils from the uvula and the medulla oblongata bilaterally.
• The two cerebellar tonsils are then retracted laterally to expose the floor of the fissure. The telachoroidea is incised from the foramen of the magendie and then followed laterally to the foramen of the luschka on both sides
Recommendation
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• The transvermian approach has a higher risk of postoperative cerebellar mutism syndrome particularly in children
Radioteraphy
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Radioteraphy
• Patient > 3th average-risk
36 Gy craniospinal irradiation (dose-reduction to 18 Gy in children aged 3 to 7 years), and a boost to the posterior fossa for a total dose of 54 G
• Patient > 3th high-risk
36 Gy craniospinal irradiation with a boost to both the posterior fossa and focal sites of metastatic disease to 55.8 Gy
52 Ilmiah Divisi Neuro-Onkologi
Chemoteraphy
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• Our findings suggest that norcantharidin has potential therapeutic applications in the treatment of medulloblastoma as a result of its ability to cross the blood-brain barrier and its impairment of Wnt-β- catenin signaling
Targetted terapy
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• Group 3 medulloblastomas are characterized by frequent amplifications of the oncogene MYC
• Genomic profiling of Group 3 medulloblastoma cells treated with alsterpaullone confirmed inhibition of cell cycle-related genes, and down-regulation of MYC.
Complication
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Complication
Surgery
RadiotherapyChemotherapy
Targeted
Surgery
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• Cerebellar mutism: decreased speech, hypotonia, ataxia and emotional instability
• First presented at the 13th Annual Meeting of Japanese Society for Paediatric
• Pathophysiology of cerebellar mutism has not been well clarified yet
• Incidence is 11%–29%
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• Ototoxicity
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• With current means of therapy, children with nondisseminated medulloblastoma 80% or more will be alive 5 years after diagnosis and treatment, with many free of the disease
Prognosis 5yr Survival
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Goal
New Improve Survival +
Quality of Life