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Glioblastoma - Diffuse guerilla war by Dr Paloma Jimenez Arribas
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Glioblastoma - Diffuse guerilla war by Dr Paloma Jimenez Arribas

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A fascinating presentation about Glioblastoma, comparing it to …

A fascinating presentation about Glioblastoma, comparing it to
Guerrila warfare by Dr Paloma Jimenez Arribas , a resident Neurosurgeon at Son Espases Hospital in Palma de Mallorca

Published in: Health & Medicine

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  • 1. DIFFUSE GLIOMA GROWTH: a guerrilla war. Dr JiménezArribas, Paloma NSG 3st year resident. May, 2014.
  • 2. Glioblastoma (GBM)  The most common and most aggressive malignant primary brain tumor in humans.  Astrocitoma grade IVWHO.  Incidence of 2–3 cases per 100,000 in Europe and North America Primary glioblastoma: the majority of GBMs. - Arise without evidence of a less malignant precursor. - Mean age 55 years. - Short clinical history (<3 months) Secondary glioblastoma: - Develops by malignant degeneration of low grade (II, III) astrocitomas. - Younger patients (mean age 40). - Slower clinical course.
  • 3. Histological findings:  Nuclear atypia  Mitosis  Neovascularization with endothelial proliferation  Areas of necrosis  “Pseudopalisading cells” • Overexpress hypoxia-inducible factor (HIF-1), and secrete proangiogenic factors. • Around areas of necrosis. • Wave of tumor cells actively migrating away from central hypoxia
  • 4. Special growth pattern:  In contrast to almost all other brain tumors, they infiltrate extensively in the neuropil (network of neuronal and glial cell processes)  This growth pattern is:  Almost unique in this kind of tumors.  A major factor in therapeutic failure.
  • 5. Special growth pattern (trough white matter): Uncinate fasciculus (simultaneous frontal and temporal lobe tumors) Corpus callosum (butterfly glioma)
  • 6. Radiological findings: Ring-enhancing lesions  Central necrotic área  Enhancing rim (active tumoral cells)  Severe perilesional edema  Radiological visualization of the invasive front is difficult  Tend to underestimate the extent of diffuse inflitrative glioma growth.
  • 7. Radiological findings:  Multifocal gliomas: multiple lesions that come from an original lesion. Usually located in the same brain hemisphere.  Multicentric gliomas: multiple lesions not originated from the same lesion.Widely separated.
  • 8. To understand the growth pattern of these tumors…. Guerrilla war metaphor
  • 9. Like guerrilla warriors….  Tumors cells tend to invade individually or in small groups in foreign territory and to abuse pre-existent supply lines.  Visualization of the invasive front is problematic.
  • 10. Like guerrilla warriors….  Glioma cells have specific qualities that allow a diffuse infiltration (Molecular background)
  • 11. Internal system that coordinates inputs and outputs (membrane receptors).
  • 12. Locomotor apparatus (dynamic remodeling of the cytoskeleton) Trails to travel (myelinated fibers migration trough white matter tracts)
  • 13. Tools to remove obstacles (proteases that degrade the ECM, cytokines that evade immune response)
  • 14. Interactions between the cells and their microenvironment that guide the way
  • 15. Like guerrilla warriors….  Conventional methods to fight glioma cells have limited effect or cause too much collateral damage (they tend to blend with normal brain), and a “search and destroy” tactic may be needed.  Treatment involves surgery, chemotherapy and radiation.  Surgery makes impossible a complete tumor removal in high grade gliomas.
  • 16. No current treatment is curative. Standard treatment consists of the following: Maximal surgical resection Radiotherapy Chemotherapy The surgical goals are:  To establish a pathologic diagnosis  To relieve any mass effect  To facilitate adjuvant therapy Maximum tumor resection, without affecting the vital brain structures and minimizing the risk of postoperative neurological deficits. Surgical options: Gross total resection (better survival) Subtotal resection Biopsy (for patients with a tumor located in an eloquent area of the brain, patients whose tumors have minimal mass effect, and patients in poor medical condition who cannot undergo general anesthesia)
  • 17. Outcome The median survival time from the time of diagnosis without any treatment is 3 months Factors affecting outcome: Patient age (the most significant prognosticator) Performance status (Karnofsky score) The extent of surgery (gross total / subtotal / biopsy) Tumor size and location
  • 18. Outcome The median survival time from the time of diagnosis without any treatment is 3 months Factors affecting outcome: Patient age (the most significant prognosticator) Performance status (Karnofsky score) The extent of surgery (gross total / subtotal / biopsy) Tumor size and location Surgery + XRT + Chemoterapy Median survival (weeks) Estimated 2-year survival < 40, frontal tumor (GTR) 132 (2,5 years) 65% < 40, Not frontal tumor (GTR) 71 (1,3 years) 35% 40<age<65 KPS > 70 GTR/STR 63 (1,2 years) 17% >65 40< age<65 + KPS <80 40<age<65 + KPS >80 + BIOPSY 37 (5 months) 4%
  • 19. Conclusions  The special growth pattern of high grade gliomas has important diagnostic, prognostic and therapeutic implications.  Diffuse gliomas are unlikely to be cured by techniques that cannot selectively destroy neoplastic cells.  Knowing the mechanisms that allow glioma cells to difussely infiltrate in the neuropil may provide new therapeutic targets for recognizing, attacking and killing these cells.  The future…. Investigational therapies (gene therapy, peptide and dendritic cell vaccines, synthetic chlorotoxins and antibodies)