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