1. Surgery for Metastatic Brain Tumor from Breast Cancer
Tanat Vaniyapong, MD
Neurosurgery Unit, Faculty of Medicine,
Chiang Mai University
8 January 2016

2. Introduction 10-30% of breast cancer  brain metastasis
 incidence (longer survival / new imaging modalities)

3. Risk factors for brain metastasis
Younger age (<50 yr)
> 2 metastatic sites
High tumor grade
Tumor size > 2 cm
HER2 positive
Triple-negative breast cancer
(Weil, 2005; Heitz, 2009)

4. Prognosis 1-year overall survival: 20% Median survival
Untreated: 4 week
WBRT: 4-6 mo
Single lesion with surgery and RT: 16 mo

5. Prognostic factors HER2 positive (worst in triple negative)
KPS > 70
Size of primary cancer
Interval from Dx  brain metastases
Number of metastasis
Age
ER status
Extracranial metastases

6. Prognostic factors
Andres, 2011, Cancer. April 15; 117(8): 1602–1611

7. Prognosis Recursive partitioning analysis (RPA)
KPS
Primary tumor status
Extracranial metastasis
Age
Graded prognostic assessment (GPA) index
Number of CNS metastasis
The Radiation Therapy Oncology Group (RTOG)

8. Prognosis Recursive partitioning analysis (RPA)
KPS
Primary tumor status
Extracranial metastasis
Age
Breast cancer – specific – GPA index
Number of CNS metastasis
HER2 and ER/PR status
The Radiation Therapy Oncology Group (RTOG)

9. Prognosis (A) GPA index 0.5 1 Age >60 50-59 <50 KPS <70 70-80
0.5 1
Age
>60
50-59
<50
KPS
<70
70-80
90-100
No. CNS metastases
>3
2-3
Extracranial metas
Present -
None
(B) Median survival
GPA
0-1
1.5-2
2.5-3
3.5-4
OS in months (All tumors)
3.1
5.4
9.6
16.7
S in months (Breast cancer)
3.4
7.7
15.1
25.3
Gil-Gil, 2014

10. Treatment of Brain Metastasis
Focal treatment
Surgical resection (Sx)
Stereotactic Radiosurgery (SRS)
Regional treatment
Whole brain Radiation (WBRT)

11. Treatment of Brain Metastasis
Treatment options
Sx+WBRT vs WBRT
Sx+WBRT vs Sx
Sx+WBRT vs SRS + WBRT
SRS vs SRS+WBRT

12. Ranasinghe, 2007: modified from Fife, 2004

13. WBRT VS Surgery + WBRT

14. WBRT VS SURGERY+WBRT 3 RCT – single brain metastasis
Patchell (48pt)
Median survival : Sx+WBRT VS WBRT alone (40 wk VS 15 wk)
Sx group had longer functional independence (38 wk VS 8 wk)
Vecht (63 pt)
Median survival Sx+WBRT VS WBRT : 10 mo VS 6 mo (p 0.04)
Mintz (84 pt)
Median survival Sx+WBRT VS WBRT: 5.6 VS 6.3 yr
No difference in cause of death and quality of life

15. Hart MG, Cochrane Review, 2004

16. Hart MG, Cochrane Review, 2004

18. WBRT VS SURGERY+WBRT
Surgery + WBRT may improve FIS but not overall survival.
Surgery + WBRT may reduce the proportion of deaths due to neurological cause esp. in a highly selected group of patients.
Operating on metastases does not confer significantly more adverse effects.
Hart MG, Cochrane Review, 2004

19. Surgery VS Surgery + WBRT

20. Sx+WBRT VS Sx alone 1 RCT Patchell 1998
Recurrence and neurological death were less likely in pt treated with Sx+WBRT
No significant in median survival

23. Selection for Resection
Age, Functional status and Extracranial disease
Recursive Partitioning Analysis (RPA) for Prognostic Factors from Radiation Therapy Oncology Group (RTOG) data
Age
Performance Status
Primary Disease
Extracranial Metastasis
Gasper 1997,Agboola 1998

24. Selection for Resection
Age, Functional status and Extracranial disease
RPA Class I:
Age ≤ 65
KPS > 70
controlled primary disease
no extracranial metastasis
RPA Class III: KPS < 70
RPA Class II: others
Median Survival (14.8, 9.9, 6.0 mo for Class I,II,III)
Gasper 1997,Agboola 1998

25. Selection for Resection
Age, Functional status and Extracranial disease
RPA Class I patients are good candidates for craniotomy and resection
RPA Class III patients – not likely to realize benefit from surgery
RPA Class II patients – carefelly selected by survival and operative risks
Agboola 1998

26. Selection for Resection
Single and multiple brain metastases
Multiple metastasis is no longer an barrier to craniotomy
Bindal 1993
56 pt with multiple brain metastases and found that survival was similar to a matched control group of pt with single metastases
Patients ≥ 4 tumors are usually poor prognosis and usually not treated surgically
Wronski 1997
No difference in overall outcome bet surgically treated pt with single or multiple metastases

27. Selection for Resection
Nontraditional indications
Significant mass effect  symptom relief or improve QoL
4 or more lesions : one is large and creating life or limb threatening
Small single lesion with extensive edema and/or refractory seizure
Extracranial suspected primary but difficult to Bx

28. Selection for Resection
Nontraditional indications
Symptomatic small tumor that have edema or necrosis and less likely to respond to RT
Recurrent metastases – may provide additional information (radionecrosis/edema)

29. Selection for Resection
Recurrent Metastases
Advantage of surgery
May improve survival and quality of life
Confirm histopathology
Local chemotherapeutic adjuncts (BCNU wafer)

30. Importance of preoperative evaluation
Patient Age and Functional Status
Disease free survival
Longer survival in longer disease-free interval
Leptomeningeal Disease
Leptomeningeal carcinomatosis associated with poor prognosis
Surgery has no significant benefit
Mainstay treatment is RT and intrathecal or systemic chemotherapy

31. Selection for Resection
Factors favorable for tumor resection
Age < 65
KPS > 70
Control of extracranial disease
Single tumor
Size < 3 cm
Surgical accessibility
Good tumor localization
Absences of leptomeningeal involvement
Undiagnosed primary site of cancer
Long disease-free survival
Local symptomatic mass effect

32. Sterotactic Biopsy Complications
Suitable for
Deeply seated lesion, near eloquent brain
Small lesion
Medically unable to tolerate GA
Suspected radio/chemosensitive tumor
Complications
Low (<1%) – most common = hemorrhage

33. Sterotactic Biopsy Advantage Disadvantage Less invasive
Accuracy/Precision
Local anesthesia
Location
Few complication
Disadvantage
Extent of removal – survival ?
Device/technic

34. Sterotactic Surgery
Framed sterotactic biopsy

35. Sterotactic Surgery Frameless stereotactic biopsy
Neuronavigation system

36. Mr. H, 60 yr, CA lung

37. P.M. 54 y , CA lung s/p resection

39. P yr

40. Mr.DK. 40 yr , CA stomach

41. P.S. 40 yr , Advanced CA lung

42. K, 52 yr

43. Summary Surgery + WBRT > Surgery Surgery + WBRT > WBRT
Good candidates
Single lesion
Age < 60
Good KPS
Controlled primary

44. Summary Surgery decision is individualized for
Poor KPS, advanced primary, multiple metastasis
Biopsy/sterotactic Bx – selected case

45. Guideline for brain metastasis in northern breast cancer patients
Symptom suspected brain metastasis
CT or MRI brain as initial investigation
Confirmed brain metastasis
- Start dexamethasone IV
- Other supportive medication
Single lesion
Multiple lesions
Consult Neurosurgeon
Consult Radiation Oncologist
Appropriate for tumor resection
Inappropriate for tumor resection
Remove tumor
followed by PORT

46. The End