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Contemporary Management of Contemporary Management of

Brain Metastases Brain Metastases
J ohn Yu, MD J ohn Yu, MD
Director, Surgical Neuro Director, Surgical Neuro- -Oncology Oncology
Department of Neurosurgery Department of Neurosurgery
Cedars Cedars- -Sinai Medical Center Sinai Medical Center
Definitions Definitions
Primary tumor Primary tumor- - original site of cancer original site of cancer
Lung, breast, melanoma, renal cell carcinoma, Lung, breast, melanoma, renal cell carcinoma,
etc. etc.
Metastasis Metastasis- - tumor cells which have tumor cells which have
migrated from the original site migrated from the original site
Brain, bone, other organs (liver metastases Brain, bone, other organs (liver metastases
with lung primary, etc.) with lung primary, etc.)
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Overview Overview
Epidemiology Epidemiology
Diagnosis Diagnosis
Imaging Imaging
Radiation: whole brain, stereotactic Radiation: whole brain, stereotactic
radiosurgery radiosurgery
Surgery Surgery
Future treatments Future treatments
Epidemiology Epidemiology
Approximately 150 Approximately 150- -170,000 annually 170,000 annually
Posner and Posner and Cherik Cherik: 24% of 2375 cancer : 24% of 2375 cancer
patients patients
Increased age 45 Increased age 45- -64 but most prevalent 64 but most prevalent
over 65 over 65
Presenting symptom of cancer in 15% Presenting symptom of cancer in 15%
Solitary site of cancer 9% Solitary site of cancer 9%
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Incidence is increasing Incidence is increasing
Increasing length of survival Increasing length of survival
Increasing rate of diagnosis Increasing rate of diagnosis
MRI MRI
PET scans PET scans
Protocols Protocols
BBB BBB- - blood blood- -brain barrier brain barrier
Relatively Relatively immunoprotected immunoprotected environment environment
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Timing of presentation Timing of presentation
Metachronous Metachronous 80% 80%
2+ 2+ mos mos from initial from initial Dx Dx
Synchronous Synchronous
Within 2 Within 2 mos mos of of Dx Dx
Precocious Precocious
Diagnosis of brain metastasis before primary Diagnosis of brain metastasis before primary
tumor tumor
Symptoms Symptoms
More dependent on location in brain and growth More dependent on location in brain and growth
rate than tumor type rate than tumor type
Headache alone 50% Headache alone 50%
Seizures 20% Seizures 20%
Hydrocephalus Hydrocephalus- - blockage of spinal fluid drainage blockage of spinal fluid drainage
Mental status changes (confusion, sleepiness) Mental status changes (confusion, sleepiness)
Tumor TIA (mini Tumor TIA (mini- -stroke) stroke)- - symptoms which symptoms which
improve improve
Asymptomatic 10% Asymptomatic 10%
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MRI MRI - - metastases vs. metastases vs. glioma glioma
(primary brain tumor) (primary brain tumor)
Multiple Multiple
Well Well- -circumscribed circumscribed
Grey Grey- -white junction white junction
Common in posterior Common in posterior
fossa fossa
Single Single
Infiltrative Infiltrative
Cortical Cortical
Uncommon in Uncommon in
posterior posterior fossa fossa
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Imaging Imaging
Screening Screening
Non small cell lung cancer Non small cell lung cancer
Breast cancer Breast cancer
Increased sensitivity on triple dose contrast, Increased sensitivity on triple dose contrast,
thin thin- -cut MRI cut MRI
Hemorrhagic Hemorrhagic
Melanoma, thyroid, renal, breast, lung Melanoma, thyroid, renal, breast, lung
Possibly CT with contrast, MRI without contrast Possibly CT with contrast, MRI without contrast
Less sensitive Less sensitive
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Physiologic imaging Physiologic imaging
PET scan PET scan

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F F- -deoxyglucose deoxyglucose
Increased cellular activity Increased cellular activity
SPECT SPECT
Perfusion MRI Perfusion MRI
MR spectroscopy (MRS) MR spectroscopy (MRS)
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Anticonvulsants Anticonvulsants
American Academy of Neurology American Academy of Neurology
Antiepileptic drugs ( Antiepileptic drugs (AEDs AEDs) not needed unless ) not needed unless
history of seizures history of seizures
Dilantin Dilantin, , phenobarbital phenobarbital
Blood levels, interference with other medications Blood levels, interference with other medications
Peri Peri- -operative coverage operative coverage- - one week one week
Unclear with newer Unclear with newer AEDs AEDs- - Keppra Keppra, , Zonegran Zonegran
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Surgical Techniques Surgical Techniques
MRI guidance MRI guidance
Intraoperative MRI Intraoperative MRI
Intraoperative ultrasound Intraoperative ultrasound
Motor strip mapping Motor strip mapping
Language mapping Language mapping
Awake craniotomy Awake craniotomy
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Patchell Patchell 1990 1990
Randomized study in single brain Randomized study in single brain mets mets
48 patients 48 patients
Improvement in median survival for surgery + Improvement in median survival for surgery +
XRT vs. XRT alone (40w. vs. 15w., p<.01) XRT vs. XRT alone (40w. vs. 15w., p<.01)
Longer functional independence (38w Longer functional independence (38w vs vs 8w, 8w,
p<.005) p<.005)
Patchell Patchell 1998 1998- - whole brain radiation after whole brain radiation after
surgery delayed surgery delayed neurologic neurologic morbidity and morbidity and
mortality (vs. surgery alone) mortality (vs. surgery alone)
Few randomized surgical trials Few randomized surgical trials
Factors favoring excision of a Factors favoring excision of a
solitary lesion solitary lesion
Primary disease controlled Primary disease controlled
Accessible lesion Accessible lesion
Symptomatic, large (> 4cm), or life Symptomatic, large (> 4cm), or life- -threatening threatening
lesion lesion
Not radiosensitive tumor (not small Not radiosensitive tumor (not small- -cell lung cell lung
carcinoma) carcinoma)
Only accessible pathology Only accessible pathology
No delay in appropriate treatment from No delay in appropriate treatment from
craniotomy craniotomy
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Factors favoring excision of Factors favoring excision of
multiple lesions multiple lesions
Primary disease controlled Primary disease controlled
Accessible lesions, less than 4 Accessible lesions, less than 4
Symptomatic, large (> 4cm), or life Symptomatic, large (> 4cm), or life- -
threatening lesions threatening lesions
Not radiosensitive tumor Not radiosensitive tumor
Only accessible pathology Only accessible pathology
No delay in appropriate treatment from No delay in appropriate treatment from
craniotomy craniotomy
Bindal Bindal, , Sawaya Sawaya 1993 1993
Resection of up to 3 accessible metastases Resection of up to 3 accessible metastases
improved survival to the same as those improved survival to the same as those
with a single metastasis with a single metastasis
SRS (stereotactic radiosurgery) is a SRS (stereotactic radiosurgery) is a
possibility possibility
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Whole Brain Radiation Therapy Whole Brain Radiation Therapy
(WB XRT) (WB XRT)
30 30 Gy Gy in 10 fractions over 2w. vs. 50 in 10 fractions over 2w. vs. 50 Gy Gy in in
2 2 Gy Gy fractions fractions
Radiosensitive Radiosensitive
SCLC, germ cell tumors, lymphoma, leukemia, SCLC, germ cell tumors, lymphoma, leukemia,
multiple multiple myeloma myeloma
Radioresistant Radioresistant
Melanoma, renal cell carcinoma, sarcoma Melanoma, renal cell carcinoma, sarcoma
Different for radiosurgery Different for radiosurgery
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XRT Complications XRT Complications
Acute < 90d Acute < 90d
N/V, alopecia, hearing loss, skin reactions, N/V, alopecia, hearing loss, skin reactions,
somnolence somnolence
Some symptoms reversible Some symptoms reversible
Late > 90d Late > 90d
Radiation necrosis, personality changes, memory loss, Radiation necrosis, personality changes, memory loss,
cognitive deficits, ataxia, incontinence cognitive deficits, ataxia, incontinence
Should be minimal if 30 Should be minimal if 30 Gy Gy in 10 fractions or in 10 fractions or
more more
Severe complications 5%; total rate higher Severe complications 5%; total rate higher
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Small cell lung cancer Small cell lung cancer
20% of lung cancer 20% of lung cancer
Oat cell cancer Oat cell cancer
Younger, smokers Younger, smokers
Median survival 6 Median survival 6- -10 mos. 10 mos.
Mets in 80% of those who survive 2y. Mets in 80% of those who survive 2y.
Radiosensitive Radiosensitive- - prophylactic WB XRT prophylactic WB XRT
Biopsy of lung lesion important when possible Biopsy of lung lesion important when possible
when facing undiagnosed lung mass and brain when facing undiagnosed lung mass and brain
mass mass
Stereotactic radiosurgery (SRS) Stereotactic radiosurgery (SRS)
Targeted radiation delivery Targeted radiation delivery
Energy sources: Energy sources:
gamma knife gamma knife- - Cobalt Cobalt- -60 60
linear accelerator (LINAC) linear accelerator (LINAC)- - electron accelerator electron accelerator
proton beam proton beam
Cyberknife Cyberknife, , Novalis Novalis- - frameless LINAC frameless LINAC
Accuracy Accuracy vs vs patient comfort patient comfort
18 18- -22 22 Gy Gy
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Surgery vs. Radiosurgery Surgery vs. Radiosurgery
Limited data on comparative efficacy Limited data on comparative efficacy
Need good systemic health for craniotomy Need good systemic health for craniotomy
Mass effect Mass effect
Significant edema Significant edema
Small, relatively inaccessible lesions Small, relatively inaccessible lesions
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Outcome Outcome
Karnofsky Karnofsky >70 (good >70 (good neurologic neurologic status) status)
Age <60 Age <60
No systemic metastases No systemic metastases
Controlled primary disease Controlled primary disease
>1y. since primary >1y. since primary Dx Dx
Solitary metastasis Solitary metastasis
Outcome Outcome
No treatment No treatment- - 1 mo. median survival 1 mo. median survival
Steroids alone Steroids alone- - 2 mos. 2 mos.
WB XRT 3 WB XRT 3- -6 mos. 50% deaths from 6 mos. 50% deaths from
intracranial progression intracranial progression
Surgery, WB XRT 12 mos. Surgery, WB XRT 12 mos.
Improved for young age, Improved for young age, unifocal unifocal and and
accessible disease, good accessible disease, good neurologic neurologic status status
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Whole brain radiation vs. Whole brain radiation vs.
radiosurgery boost after surgery radiosurgery boost after surgery
Whole brain essentially cannot be Whole brain essentially cannot be
repeated repeated
Assumes that primary tumor seeding the Assumes that primary tumor seeding the
brain is a one brain is a one- -time event time event
Assumes that survival does not generally Assumes that survival does not generally
last long enough to see side effects of last long enough to see side effects of
whole brain radiation whole brain radiation
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Surgery + whole brain vs. Surgery + whole brain vs.
radiosurgery boost radiosurgery boost
Cancer treatment centers disagree Cancer treatment centers disagree
May recommend whole brain for any patient May recommend whole brain for any patient
with one metastasis, even after surgery with one metastasis, even after surgery
Risk of complications of whole brain radiation Risk of complications of whole brain radiation
May recommend radiosurgery boost after May recommend radiosurgery boost after
surgery, assuming close follow surgery, assuming close follow- -up with up with MRIs MRIs
Risk of distant recurrence Risk of distant recurrence
May need radiosurgery, whole brain radiation in May need radiosurgery, whole brain radiation in
future future
Follow closely with Follow closely with MRIs MRIs (e.g., every 3 months) (e.g., every 3 months)
Summary Summary
Surgical resection of brain metastases should be Surgical resection of brain metastases should be
considered for patients with limited disease in considered for patients with limited disease in
good condition good condition
After surgery After surgery- - whole brain radiation vs. radiosurgery whole brain radiation vs. radiosurgery
boost boost
Radiosurgery Radiosurgery- - difficult to remove, poor condition difficult to remove, poor condition
for surgery, poor control of overall cancer for surgery, poor control of overall cancer
Whole brain radiation 4+ lesions, SCLC Whole brain radiation 4+ lesions, SCLC
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Unanswered questions Unanswered questions
Is the rate of distal failure when avoiding Is the rate of distal failure when avoiding
WB XRT significant to the patient? WB XRT significant to the patient?
Is there a more sensitive method for Is there a more sensitive method for
detecting micro detecting micro- -metastases than MRI? metastases than MRI?
Is there a benefit to WB XRT after Is there a benefit to WB XRT after
radiosurgery? radiosurgery?
Is there a benefit with low risks to Is there a benefit with low risks to
radiosurgery after whole brain radiation? radiosurgery after whole brain radiation?
Ongoing studies Ongoing studies
European European Organisation Organisation for Research and for Research and
Treatment of Cancer (EORTC) 22952 Treatment of Cancer (EORTC) 22952- -
comparison of surgery and radiosurgery comparison of surgery and radiosurgery
+/ +/- - XRT XRT
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New treatments New treatments
Temodar Temodar
Alkylating Alkylating agent which crosses BBB agent which crosses BBB
Gliadel Gliadel (BCNU) (BCNU)
Chemo wafer placed across the BBB Chemo wafer placed across the BBB
XRT or SRS? XRT or SRS?
Is local vs. distant disease the problem? Is local vs. distant disease the problem?
Radiosensitizers Radiosensitizers
Efaproxiral Efaproxiral, , motexafin motexafin gadolinium gadolinium
Microwave ablation Microwave ablation