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Glioblastoma multiforme
4	 week	 history	 of	 67	 years-old	 caucasian	                       headache	 “especially	 male	 patient,	 no	          ...
The	 most	 common	 primary	 brain	 tumors	 are	 the	            gliomas	 (approximately	 60%)Among	 all	 gliomas,	 Gliobla...
Classification        Pilocytic	 astrocytoma	 (WHO	 I)                Diffuse	 astrocytoma	 (WHO	 II)                Anapl...
EpidemiologyMost	 common	 primary	 brain	 tumor	 (15%)        2-3	 new	 cases	 per	 100.000	 people/y                   It...
Rarely,	 glioblastomas	 presents	 with	 meningeal	 dissemination,	 causing	 meningeal	 gliomatosis	 symptoms
Prognostic  factors
Prognostic  factors Tumor grade
Prognostic  factors Tumor grade    Age
Prognostic  factors Tumor grade    Age  Extent of   surgery
Prognostic  factors Tumor grade     Age  Extent of   surgery Karnofsky PS
Prognostic	 factors	 for	 survival	 of	 patients	 with	 glioblastoma:	 Recursive	 partitioning	 analysis.	 Neuro-	 oncolog...
CT scan results	 provide	 a	    high	 degree	 of	 confidence	 for	 this	 type	 of	 tumor	 but	   it	 is	 not	 usually	    ...
MRI is	 the	 most	 useful	 technique
MRI is	 the	 most	 useful	 technique                       low signal                          area
MRI is	 the	 most	 useful	 technique                       low signal                          area    cystic areas
MRI is	 the	 most	 useful	 technique                       low signal                          area    cystic areas intern...
MRI is	 the	 most	 useful	 technique                       low signal                          area    cystic areas intern...
high signal   area
high signal   area      hemorrhagic        and flow          voids
high signal        area           hemorrhagic             and flow               voidsmidline shift  and mass   effect
high signal        area           hemorrhagic             and flow               voidsmidline shift  and mass   effect    ...
PET scanning is	 a	 useful	 adjunct	 in	 GBM	 cases,	 especially	                     in	 the	 follow-up	 after	 resection...
Treatment   is	 consistent	 with   3typical	 procedures:                                  SURGERY               RADIATIONC...
The	 initial	 treatment	 for	 GBM	 is	 total	 resection	              with	 preservation	 of	 neurologic	 function    preo...
Biopsy Subtotal	 resectionGross	 total	 resection
Biopsy Subtotal	 resection   cutout at      78%Gross	 total	 resection
Radiation	 dose	 of	 6000	 cGy	 administered	 in	 5	     days	 showed	 a	 median	 survival	 of	 42	 weeks    Temozolomide	...
Genetic backgroundand new treatments
Alterations	 of	 receptor	 tyrosine	 kinases	 (such	 as	 EGFR)	 that	 activate	 PI3K	 signaling,	 leading	 to	 hyperprolif...
VEGF:	 bevacizumab,	 cediranib,	 XL184,	 enzastaurinEGFR:	 nimotuzumabPDGF:	 imatinib                                     ...
VEGF:	 bevacizumab,	 cediranib,	 XL184,	 enzastaurinEGFR:	 nimotuzumabPDGF:	 imatinib     Patients should Vaccines        ...
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  1. 1. Glioblastoma multiforme
  2. 2. 4 week history of 67 years-old caucasian headache “especially male patient, no when I wake up”, significant PMH memory loss; right- sided mild motor weakness T1-weighted axial MRI with T2-weighted axial MRI intravenous contrast
  3. 3. The most common primary brain tumors are the gliomas (approximately 60%)Among all gliomas, Glioblastoma is the most common and most aggressive tumor“Glioblastomas are densely cellular, pleomorphic tumors with mitotic activity and either microvascular proliferation or necrosis” (UpToDate 2012)
  4. 4. Classification Pilocytic astrocytoma (WHO I) Diffuse astrocytoma (WHO II) Anaplastic astrocytoma (WHO III) Glioblastoma (WHO IV)
  5. 5. EpidemiologyMost common primary brain tumor (15%) 2-3 new cases per 100.000 people/y It affects >45 adults preferentially Men to female ratio 3:2 slightly more common in whites Overall median survival after optimal therapy is less then 12 months
  6. 6. Rarely, glioblastomas presents with meningeal dissemination, causing meningeal gliomatosis symptoms
  7. 7. Prognostic factors
  8. 8. Prognostic factors Tumor grade
  9. 9. Prognostic factors Tumor grade Age
  10. 10. Prognostic factors Tumor grade Age Extent of surgery
  11. 11. Prognostic factors Tumor grade Age Extent of surgery Karnofsky PS
  12. 12. Prognostic factors for survival of patients with glioblastoma: Recursive partitioning analysis. Neuro- oncology 2004; 6:231. Copyright © 2004 Duke University Press.
  13. 13. CT scan results provide a high degree of confidence for this type of tumor but it is not usually adopted
  14. 14. MRI is the most useful technique
  15. 15. MRI is the most useful technique low signal area
  16. 16. MRI is the most useful technique low signal area cystic areas
  17. 17. MRI is the most useful technique low signal area cystic areas internal high signal areas
  18. 18. MRI is the most useful technique low signal area cystic areas internal high signal areas irregular enhanced border
  19. 19. high signal area
  20. 20. high signal area hemorrhagic and flow voids
  21. 21. high signal area hemorrhagic and flow voidsmidline shift and mass effect
  22. 22. high signal area hemorrhagic and flow voidsmidline shift and mass effect diffuse edema
  23. 23. PET scanning is a useful adjunct in GBM cases, especially in the follow-up after resection Differential diagnosis between recurrent or residual masses and scars or radiation necrosis is difficult with MRI - TC PET scans is helpful in these cases
  24. 24. Treatment is consistent with 3typical procedures: SURGERY RADIATIONCHEMOTHERAPY
  25. 25. The initial treatment for GBM is total resection with preservation of neurologic function preoperative imaging MRI - PET frameless stereotaxis with cortical stimulation and language assessments intraoperative techniques operating rooms equipped with CT - MRI scanners can guide the resection in “real time”
  26. 26. Biopsy Subtotal resectionGross total resection
  27. 27. Biopsy Subtotal resection cutout at 78%Gross total resection
  28. 28. Radiation dose of 6000 cGy administered in 5 days showed a median survival of 42 weeks Temozolomide has been shown to improve:median progression-free survival (+2 months)overall survival (+2 months)likelihood of being alive in 2 years (26% vs 10%)
  29. 29. Genetic backgroundand new treatments
  30. 30. Alterations of receptor tyrosine kinases (such as EGFR) that activate PI3K signaling, leading to hyperproliferation and increased cell survival Dysregulation of the p53 pathway that lead to effects such as reduced apoptosis L o s s o f c e l l - c y c l e c o n t r o l v i a disruption of Rb signaling pathway
  31. 31. VEGF: bevacizumab, cediranib, XL184, enzastaurinEGFR: nimotuzumabPDGF: imatinib VaccinesIntegrin inbitor: cilengitide Gene therapyHistone deactylase hinibitors: cilengitide, thalidomide Intratumoral drug Radio- administration: immunoconjugates carmustine polymer wafer, CED
  32. 32. VEGF: bevacizumab, cediranib, XL184, enzastaurinEGFR: nimotuzumabPDGF: imatinib Patients should Vaccines beIntegrin inbitor: cilengitide Gene therapy encouraged toHistone deactylase hinibitors: cilengitide, thalidomide participate in clinical Intratumoralstudies whenever drug Radio- administration: immunoconjugates possible carmustine polymer wafer, CED
  33. 33. Thank you

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