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Multiple Craniotomies Multiple Craniotomies in the Management of Multifocal and in the Management of Multifocal and
Multicentric GlioblastomaMulticentric Glioblastoma
Raymond Sawaya, M.D.
MultipleMultiple GBM Lesions are not GBM Lesions are not RareRare
GlioblastomaGlioblastoma
Multiple Synchronous GliomasMultiple Synchronous Gliomas
~ ~ 0.5 – 20% 0.5 – 20%
PathogenesisPathogenesis
Not Clearly UnderstoodNot Clearly Understood Zülch, 1957Zülch, 1957
Metastasis ?Metastasis ?
Willis, 1967Willis, 1967 multi-focal growthmulti-focal growth
Kyritsis et al.,1994Kyritsis et al.,1994 p53 gene mutation (? Genetic p53 gene mutation (? Genetic
Background)Background)
Management ?Management ?
LiteratureLiterature
Questions more than answersQuestions more than answers Case Reports and 3 SeriesCase Reports and 3 Series
LiteratureLiteratureCase Reports
Ampil et al., 2007
Int. J. Radiation Oncology Biol. Phys., Vol. 69, No. 3, pp. 820–824, 2007Int. J. Radiation Oncology Biol. Phys., Vol. 69, No. 3, pp. 820–824, 2007
50 patients with MF GBM (1995-2005)50 patients with MF GBM (1995-2005)
The Policy:The Policy: Remove one tumor focusRemove one tumor focus
WBRT or 3D Conformal RTWBRT or 3D Conformal RT
Concurrent Chemotherapy 42%Concurrent Chemotherapy 42%
Median Survival 8.1 monthsMedian Survival 8.1 months
40 patients with Multiple CNS Tumors (1988-40 patients with Multiple CNS Tumors (1988-
1993)1993) 10 Multicentric10 Multicentric
30 Multifocal30 Multifocal
The Policy:The Policy: Removal of all tumor(s) [no description]Removal of all tumor(s) [no description]
RadiotherapyRadiotherapy
30 patients received Chemotherapy30 patients received Chemotherapy
Salvati et al., 1997 Cont.Salvati et al., 1997 Cont.
51 patients with MF Gliomas (1988-51 patients with MF Gliomas (1988-
1992)1992) Describes the Radiological Describes the Radiological
Characteristics with No Comments on Characteristics with No Comments on
the Management the Management The Median Survival Time was 6 The Median Survival Time was 6
monthsmonths
European Journal of Radiology, 16 (1993) 163-170
Illustrative CaseIllustrative Case
47 y/o M; Anesthesiologist 47 y/o M; Anesthesiologist
H/A, Focal seizure in the Lt H/A, Focal seizure in the Lt
LegLeg
Neurological Exam: NormalNeurological Exam: Normal
Under review
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
ObjectivesObjectives
ComplicationsComplicationsDo multiple craniotomies increase Do multiple craniotomies increase
the risks to the patients?the risks to the patients?
SurvivalSurvivalIs the overall survival with multiple Is the overall survival with multiple
lesions who undergo extensive lesions who undergo extensive resections, similar to that of patients resections, similar to that of patients with a single lesion?with a single lesion?
Multicentric vs. MultifocalMulticentric vs. Multifocal
Multicentric Multifocal
T1 + C
Flair
Study DesignStudy Design
Study period: 1993-2008
Matching Factors (1:1 Matching Factors (1:1 Ratio)Ratio)
6000 surgically treated GBM6000 surgically treated GBM 20 controls20 controls
Preop KPS scorePreop KPS score Extent of resectionExtent of resection Age at surgeryAge at surgery Year of surgerYear of surgeryy Tumor Functional GradeTumor Functional Grade
Clinical CharacteristicsClinical Characteristics
Characteristic CasesMF/MC
ControlsSolitary
Age, Median, range 52, (32-78) 52, (31-75)
Median KPS; Range 80; 50-100 80; 50-100
Gender (%)
M 14(70) 7(35)
F 60 (30) 13(65)
Clinical CharacteristicsClinical CharacteristicsTumor NO.Tumor NO.
CasesMF/MC
ControlsSolitary
1 0 20
2 18 (90) 0
3 2 (10) 0
Clinical CharacteristicsClinical CharacteristicsLocationLocation
CasesMF/MC
ControlsSolitary
All Right 9 (45) 9 (45)
All Left 6 (30) 11 (55)
Right and Left 5 (25) 0
Clinical CharacteristicsClinical CharacteristicsTumor Worst Functional GradeTumor Worst Functional Grade
TFG CasesMF/MC
ControlsSolitary
Non or Near Eloquent Brain
12 (60) 12 (60)
Eloquent Brain 8 (40) 8 (40)
Clinical CharacteristicsClinical CharacteristicsTumor StatusTumor Status
CasesMF/MC
ControlsSolitary
All New 11 (55) 9 (45)
New and Recurrent
9 (45) 0
All Recurrent 0 10 (50)
All Residual 0 1 (5)
The Study included New and Recurrent Lesions
Clinical CharacteristicsClinical CharacteristicsSymptomsSymptoms
Symptom CasesMF/MC
ControlsSolitary
Motor deficit 7 (35) 11 (55)
Speech Deficit 6 (30) 6 (30)
Memory Deficit 6 (30) 3 (15)
Visual Deficit 6 (30) 4 (20)
HA 4 (20) 8 (40)
Altered Mental Status 3 (15) 3 (15)
Unstable Gait 3 (15) 2 (10)
Sensory Deficit 3 (15) 1 (5)
Cranial Nerve Deficit 3 (15) 0
Seizures 2 (10) 4 (20)Patient may have > 1 symptom
Clinical CharacteristicsClinical CharacteristicsManagementManagement
CasesMF/MC
ControlsSolitary
No. of Craniotomies
1 0 20 (100)
2 20 (100) 0
Circumferential Resection
10 (50) 12 (60)
Median % EOR, Range 100; 75-100 100; 80-100
Clinical CharacteristicsClinical CharacteristicsManagement Cont.Management Cont.
CasesMF/MC
ControlsSolitary
p Value
Radiotherapy* 100% 100% 0.75
Chemotherapy 45% 90% 0.13
* Except for 3 patients who lost to follow up in each group
Postop. ComplicationsPostop. ComplicationsCategory Multiple
Craniotomies(Cases)
Single Craniotomy(Controls)
p Value
Overall Complications
6 (30) 7 (35) 1.0
Overall Major 2 (10) 7 (35) 0.13
Neurological 5 (25) 6 (30) 1.0
Major Neurological
2 (10) 6 (30) 0.24
Regional 2 (10) 0 0.49
Major Regional 0 0 N/A
Systemic 1 (5) 2 (10) 1.0
Major Systemic 1 (5) 1 (5) 1.0
Mortality 1 (5) 0
Overall SurvivalOverall Survival
2 Patients still alive in each 2 Patients still alive in each GroupGroup
CasesMF/MC
ControlsSolitary
Median Survival 9.7 mos 10.5 mos
(P= 0.34)
Overall Overall Survival (Group)Survival (Group)
KPS > 80Solitary
MF/MC
Overall SurvivalOverall Survival
MulticentricMulticentric 12.9 mos12.9 mos
Multifocal Multifocal 9.6 mos9.6 mos
Overall Survival for Overall Survival for New New LesionsLesions
MulticentricN = 5
MultifocalN = 6
SolitaryN = 9
12.9 mos 9.6 mos 14.6 mos
(P= 0. 014)
Overall Overall Survival (New Survival (New Lesions)Lesions)
En Bloc Resection Solitary
MCMF
F/U at 1 yearF/U at 1 year
F/U at 16 mosF/U at 16 mos
Limitations of the Limitations of the StudyStudy Retrospective Case SeriesRetrospective Case Series Small sample sizeSmall sample size Highly selected cases Highly selected cases Patients treated by other modalities Patients treated by other modalities
(biopsy, resection of one lesion….) (biopsy, resection of one lesion….)
were not included in the study. were not included in the study.
ConclusionsConclusions
Morbidity: Morbidity:
Multiple Craniotomies appear similar to Multiple Craniotomies appear similar to
Single Single CraniotomiesCraniotomies Survival: Survival:
MF and MC GBM may benefit from MF and MC GBM may benefit from complete complete resection of all the lesionsresection of all the lesions
Future Studies: Future Studies: Prospective Assessment of the role of Prospective Assessment of the role of
Multiple Multiple Craniotomies in the management of Craniotomies in the management of MF MC MF MC glioblastomasglioblastomas