Multiple Craniotomies in the Management of Multifocal and Multicentric Glioblastoma

1. Multiple Craniotomies in the Management of Multifocal and Multicentric Glioblastoma Raymond Sawaya, M.D.

3. Multiple GBM Lesions are not Rare Glioblastoma Multiple Synchronous Gliomas ~ 0.5 – 20%

4. Pathogenesis • Not Clearly Understood • Zülch, 1957 • Metastasis ? • Willis, 1967 • multi-focal growth • Kyritsis et al.,1994 •  p53 gene mutation (? Genetic Background)

5. Management ?

6. Literature • Questions more than answers • Case Reports and 3 Series

7. Literature Case Reports Ampil et al., 2007

8. Int. J. Radiation Oncology Biol. Phys., Vol. 69, No. 3, pp. 820–824, 2007 • 50 patients with MF GBM (1995-2005) • The Policy: • Remove one tumor focus • WBRT or 3D Conformal RT • Concurrent Chemotherapy 42% Median Survival 8.1 months

9. 40 patients with Multiple CNS Tumors (1988-1993) • 10 Multicentric • 30 Multifocal • The Policy: • Removal of all tumor(s) [no description] • Radiotherapy • 30 patients received Chemotherapy

10. Salvati et al., 1997 Cont.

11. 51 patients with MF Gliomas (1988-1992) • Describes the Radiological Characteristics with No Comments on the Management • The Median Survival Time was 6 months European Journal of Radiology, 16 (1993) 163-170

12. Illustrative Case • 47 y/o M; Anesthesiologist • H/A, Focal seizure in the Lt Leg • Neurological Exam: Normal

14. Multiple craniotomies in the management of multifocal and multicentric glioblastoma Wael Hassaneen, MD, Nicholas B. Levine, MD, Dima Suki, PhD, Abbhijit Salaskar, MBBS, Alessandra de Moura Lima, Ian McCutcheon, MD, Sujit Prabhu, MD, Frederick F. Lang, MD, Franco DeMonte, MD, Ganesh Rao, MD, Jeffrey S. Weinberg, MD, David Wildrick PhD, Ken Aldape, MD, and Raymond Sawaya, MD Under review

15. Objectives • Complications • Do multiple craniotomies increase the risks to the patients? • Survival • Is the overall survival with multiple lesions who undergo extensive resections, similar to that of patients with a single lesion?

16. Multicentric vs. Multifocal T1 + C Flair Multicentric Multifocal

17. Study Design Study period: 1993-2008

18. Matching Factors (1:1 Ratio) 6000 surgically treated GBM • 20 controls • Preop KPS score • Extent of resection • Age at surgery • Year of surgery • Tumor Functional Grade

19. Clinical Characteristics

20. Clinical CharacteristicsTumor NO.

21. Clinical CharacteristicsLocation

22. Clinical CharacteristicsTumor Worst Functional Grade

23. Clinical CharacteristicsTumor Status The Study included New and Recurrent Lesions

24. Clinical CharacteristicsSymptoms Patient may have > 1 symptom

25. Clinical CharacteristicsManagement

27. Clinical CharacteristicsManagement Cont. * Except for 3 patients who lost to follow up in each group

28. Postop. Complications

29. Overall Survival • 2 Patients still alive in each Group (P= 0.34)

30. Overall Survival (Group) KPS > 80 Solitary MF/MC

31. Overall Survival • Multicentric • 12.9 mos • Multifocal • 9.6 mos

32. Overall Survival for New Lesions (P= 0. 014)

33. Overall Survival (New Lesions) En Bloc Resection Solitary MF MC

34. F/U at 1 year

35. F/U at 16 mos

36. Limitations of the Study • Retrospective Case Series • Small sample size • Highly selected cases • Patients treated by other modalities (biopsy, resection of one lesion….) were not included in the study.

37. Conclusions • Morbidity: Multiple Craniotomies appear similar to Single Craniotomies • Survival: MF and MC GBM may benefit from complete resection of all the lesions • Future Studies: Prospective Assessment of the role of Multiple Craniotomies in the management of MF MC glioblastomas