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 Willis, 1967
Metastasis ?
Willis, 1967
multi-focal growth
Kyritsis et al.,1994
 p53 gene mutation (? Genetic Background)

5. Management ?
Biopsy
Radiation
Resection

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

7. Literature
Case Reports
Ampil et al., 2007

8. 50 patients with MF GBM (1995-2005) The Policy:
Int. J. Radiation Oncology Biol. Phys., Vol. 69, No. 3, pp. 820–824, 2007
50 patients with MF GBM ( )
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)
European Journal of Radiology, 16 (1993)
51 patients with MF Gliomas ( )
Describes the Radiological Characteristics with No Comments on the Management
The Median Survival Time was 6 months

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 Survival
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 Cases MC MF Controls Solitary 9 patients 11 patients
Study period:

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
Cases
MF/MC
Controls
Solitary
Age, Median, range
52, (32-78)
52, (31-75)
Median KPS; Range
80;
Gender (%) M
14(70)
7(35) F
60 (30)
13(65)

20. Clinical Characteristics Tumor NO.
Cases
MF/MC
Controls
Solitary 1 20 2
18 (90) 3
2 (10)

21. Clinical Characteristics Location
Cases
MF/MC
Controls
Solitary
All Right
9 (45)
All Left
6 (30)
11 (55)
Right and Left
5 (25)

22. Clinical Characteristics Tumor Worst Functional Grade
TFG
Cases
MF/MC
Controls
Solitary
Non or Near Eloquent Brain
12 (60)
Eloquent Brain
8 (40)

23. Clinical Characteristics Tumor Status
The Study included New and Recurrent Lesions
Cases
MF/MC
Controls
Solitary
All New
11 (55)
9 (45)
New and Recurrent
All Recurrent
10 (50)
All Residual
1 (5)

24. Clinical Characteristics Symptoms
Cases
MF/MC
Controls
Solitary
Motor deficit
7 (35)
11 (55)
Speech Deficit
6 (30)
Memory Deficit
3 (15)
Visual Deficit
4 (20) HA
8 (40)
Altered Mental Status
Unstable Gait
2 (10)
Sensory Deficit
1 (5)
Cranial Nerve Deficit
Seizures
Patient may have > 1 symptom

25. Clinical Characteristics Management
Cases
MF/MC
Controls
Solitary
No. of Craniotomies 1
20 (100) 2
Circumferential Resection
10 (50)
12 (60)
Median % EOR, Range
100;
100;

27. Clinical Characteristics Management Cont.
Cases
MF/MC
Controls
Solitary
p Value
Radiotherapy*
100%
0.75
Chemotherapy
45%
90%
0.13
* Except for 3 patients who lost to follow up in each group

28. Multiple Craniotomies
Postop. Complications
Category
Multiple Craniotomies
(Cases)
Single Craniotomy
(Controls)
p Value
Overall Complications
6 (30)
7 (35)
1.0
Overall Major
2 (10)
0.13
Neurological
5 (25)
Major Neurological
0.24
Regional
0.49
Major Regional
N/A
Systemic
1 (5)
Major Systemic
Mortality

29. Overall Survival 2 Patients still alive in each Group Cases Controls
MF/MC
Controls
Solitary
Median Survival
9.7 mos
10.5 mos
(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
Multicentric N = 5
Multifocal N = 6
Solitary N = 9
12.9 mos
9.6 mos
14.6 mos
(P= )

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