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  • 1. Evidence-Based Surgery Multiple Brain Metastases - Efficacy ofGamma Knife Surgery as sole therapy in a known primary Sanmugarajah Paramasvaran John Fuller 12th April 2012 1
  • 2. Clinical Case• 38 yr lady• Ca Breast 2008, lumpectomy• Metastasis to spine, pelvis 2009• Chemotherapy and RT• Multiple brain Metastasis July 2011• GKS 2
  • 3. • Pre GKS • 3 months post GKS 3
  • 4. Clinical Questions: Does GKS as sole therapy in multiple brain metastasis improve median and progression free survival in comparison to surgery? 4
  • 5. Search strategy• P = Patients with multiple brain metastases• I = Gamma Knife Surgery• C = Surgery• O = Survival benefitSearch Keywords (exp MESH )1) “Brain Metastases” “Brain Neoplasm/sc” “Gamma Knife” “Treatment Outcome”2) “Brain Metastases” “ Brain Neoplasm/sc” “Neurosurgical procedures” 5
  • 6. Search Results • 4 relevant for GK • 1 relevant for surgery 6
  • 7. Scopus 6 relevant for GKS 1 relevant for surgery 7
  • 8. Cochrane Nil 8
  • 9. Selection Criteria• Multiple brain metastases• GKS• Surgery• English LanguageExclusions: WBRT 9
  • 10. Levels of Evidence (NHMRC)All papers – Class IV 10
  • 11. Summary of findings for GKSAuthor/Center/year No Type of Criteria MS PFS study (mo) (mo)Toru Serizawa et al 1508 Retro 1)1–10 brain lesions A)SingleJapan,Multicenter 2)less than 10 cm3 volume lesion: 122010 of the largest tumor B) 2-4 3) Karnofsky Performance lesions: Scale score < 70 8.16 C) 5-10 Lesions:7. 41Nicolas Dea et al 164 Retro 1)Eloquent area 8.2 16Université de 2)KPS > 50Sherbrooke,Canada 5.7%2010 transient neurology 11
  • 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 GroupUniversity College of lesions; 4:Medicine, Seoul Group 2: 6–10 10 more2010 lesions: new Group 3: 11–15 13 lesions lesions; Group 4: > 15 8 lesionsYamamoto et al 456 Retro All had only GKJapan 1-4 85% of2009 lesions: death 7.4 – non >4 neurol lesions: ogical 4 12
  • 13. Author/Center/y No Type of Criteria/Methods MS PFS/Otherear study (mo) (mo)Jawahar et al 48 Retro All only GKS 12 70%2004 improvement in neurologyChang-Hyun Kim 26 1) 10 or > lesions 8.2 Local controlSeoul,Korea 2) KPS > 70 in 79.5% in 62008 3) RPA 1& 2 months New lesions- (mean no of lesion; 26.9% 16.6) 1 radiation necrosis 13
  • 14. Author/Center/year No Type Criteria/Methods MS PFS /Others of (mo) (mo) studyAndreas Schoegg et 97 Retro No of mets ; 2-4 6alVienna, 1999 To look for  KPS>70 pronostic factors No extracranial disease 9.2Chul-Kyu Lee et al 36 Retro  4-14 lesions 9.1±1.7 local tumorSeoul Mean KPS 90 control rates a2011 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 surgeryAuthor/Center/Year No Type of Criteria/Methods OS PFS study (mo) /Others (mo)Sun Ha Paek Retro 191 – single mets 8Seoul National Uni 17 – 2 or more 92005Bindal et al 56 Retrosp Group A: no resection 6MD 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) 16
  • 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) 17
  • 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. 18
  • 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 19
  • 20. 20
  • 21. Median survival 21
  • 22. 22
  • 23. Complications 23
  • 24. • the only variables significantly affecting survival were the patient group presence of systemic disease Remove all accessible lesions, in limited systemic disease 24
  • 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 25
  • 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 lesionsLimitation:• Lesion size 26
  • 27. ConclusionRetrospective 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 27
  • 28. Thank You 28