1. Evidence-Based Surgery
Multiple Brain Metastases - Efficacy of
Gamma Knife Surgery as sole therapy in a
known primary
Sanmugarajah Paramasvaran
John Fuller
12th April 2012
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2. Clinical Case
• 38 yr lady
• Ca Breast 2008, lumpectomy
• Metastasis to spine, pelvis 2009
• Chemotherapy and RT
• Multiple brain Metastasis July 2011
• GKS
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3. • Pre GKS • 3 months post GKS
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4. Clinical Questions:
 Does GKS as sole therapy in multiple brain
metastasis improve median and progression
free survival in comparison to surgery?
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5. Search strategy
• P = Patients with multiple brain metastases
• I = Gamma Knife Surgery
• C = Surgery
• O = Survival benefit
Search Keywords (exp MESH )
1) “Brain Metastases” “Brain Neoplasm/sc” “Gamma
Knife” “Treatment Outcome”
2) “Brain Metastases” “ Brain Neoplasm/sc”
“Neurosurgical procedures”
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6. Search Results
• 4 relevant
for GK
• 1 relevant
for
surgery
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7. Scopus
6 relevant for
GKS
1 relevant for
surgery
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8. Cochrane
Nil
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9. Selection Criteria
• Multiple brain metastases
• GKS
• Surgery
• English Language
Exclusions:
 WBRT
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10. Levels of Evidence (NHMRC)
All papers – Class IV
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11. Summary of findings for GKS
Author/Center/year No Type of Criteria MS PFS
study (mo) (mo)
Toru Serizawa et al 1508 Retro 1)1–10 brain lesions A)Single
Japan,Multicenter 2)less than 10 cm3 volume lesion: 12
2010 of the largest tumor B) 2-4
3) Karnofsky Performance lesions:
Scale score < 70 8.16
C) 5-10
Lesions:7.
41
Nicolas Dea et al 164 Retro 1)Eloquent area 8.2 16
Université de 2)KPS > 50
Sherbrooke,Canada 5.7%
2010 transient
neurology
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12. Author/Center/year No Type of Criteria/Methods MS PFS
study (mo) (mo)
Won Seok Chan et al 323 Retro Group 1: 1–5 10 Group
University College of lesions; 4:
Medicine, Seoul Group 2: 6–10 10 more
2010 lesions: new
Group 3: 11–15 13 lesions
lesions;
Group 4: > 15 8
lesions
Yamamoto et al 456 Retro All had only GK
Japan 1-4 85% of
2009 lesions: death
7.4 – non
>4 neurol
lesions: ogical
4
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13. Author/Center/y No Type of Criteria/Methods MS PFS/Other
ear study (mo) (mo)
Jawahar et al 48 Retro All only GKS 12 70%
2004 improvement in
neurology
Chang-Hyun Kim 26 1) 10 or > lesions 8.2 Local control
Seoul,Korea 2) KPS > 70 in 79.5% in 6
2008 3) RPA 1& 2 months
New lesions-
(mean no of lesion; 26.9%
16.6) 1 radiation
necrosis
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14. Author/Center/year No Type Criteria/Methods MS PFS /Others
of (mo) (mo)
study
Andreas Schoegg et 97 Retro No of mets ; 2-4 6
al
Vienna, 1999 To look for  KPS>70
pronostic factors No
extracranial
disease
9.2
Chul-Kyu Lee et al 36 Retro  4-14 lesions 9.1±1.7 local tumor
Seoul Mean KPS 90 control rates a
2011 Mean Tumour 3: 92.5%,
volume 1.22 cc 6: 87.9%
9 : 84.2%,
New brain
metastasis
:22%
14
(retreated)

15. Summary of papers on surgery
Author/Center/Year No Type of Criteria/Methods OS PFS
study (mo) /Others
(mo)
Sun Ha Paek Retro 191 – single mets 8
Seoul National Uni 17 – 2 or more 9
2005
Bindal et al 56 Retrosp Group A: no resection 6
MD Anderson,US ective (30)
1993 GroupB : resection of all 14
(26)
Group C ; single mets 14
resection
match by type of primary
tumor, time from first
15
diagnosis of cancer to

16. • retrospectively reviewed
• 1508 consecutive cases
• inclusion criteria:
1) newly diagnosed brain metastases,
2) 1–10 brain lesions,
3) less than 10 cm3 volume of the largest tumor, 4) no more than 15 cm3
total tumor volume, 5) no findings of CSF
dissemination, and 6) Karnofsky Performance Scale score < 70)
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17. • all visible lesions were irradiated with GKS without
upfront whole-brain radiation therapy.
• MR imaging was performed every 2–3 months
• Group A, single lesions (565 cases);
• Group B, 2–4 tumors (577 cases);
• Group C, 5–10 tumors (366 cases)
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18. Results
 Overall survival
• 0.99 years for Group A,
• 0.68 years for Group
• B, and
• 0.62 years for Group C.
CI of 1.265 for the hazard ratio
Show efficacy of GKS as sole treatment for patients
with 5–10 brain metastases compared with those with
2–4 in terms of OS.
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19. • retrospective review
• 56 patients
• (Group A) 30 with1or more lesions left unresected
• (Group B) 26 underwent resection of all lesions
• (Group C) 26 single metastasis who underwent resection
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20. 20

21. Median survival
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22. 22

23. Complications
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24. • the only variables significantly affecting survival were
 the patient group
 presence of systemic disease
 Remove all accessible lesions, in limited
systemic disease
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25. Discussion
• Overall survival with GKS : 8 -12 months
• No of mets does not influence outcome
• Prognostic factors : Age,KPS,controlled
extracranial disease
• Overall survival with surgery : 8 -14 months
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26. Advocates of GKS
• All lesions can be treated in one session
• No perioperative complications
• Very low incidence of radiation necrosis
• Surgery is shown for upto 3 lesions
Limitation:
• Lesion size
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27. Conclusion
Retrospective study shows GKS as sole
therapy for multiple brain metastsis is as
effective as surgery and can treat more
lesions at a single session with a lesser
incidence of complications.
Randomized control trials are needed
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28. Thank You
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