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

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

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)

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

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

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

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)

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)

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

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

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

Ranasinghe, 2007: modified from Fife, 2004

WBRT VS Surgery + WBRT

WBRT VS SURGERY+WBRT 3 RCT – single brain metastasis Patchell 1990 (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 1993 (63 pt) Median survival Sx+WBRT VS WBRT : 10 mo VS 6 mo (p 0.04) Mintz 1996 (84 pt) Median survival Sx+WBRT VS WBRT: 5.6 VS 6.3 yr No difference in cause of death and quality of life

Hart MG, Cochrane Review, 2004

Hart MG, Cochrane Review, 2004

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

Surgery VS Surgery + WBRT

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

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

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

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

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

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

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)

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

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

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

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

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

Sterotactic Surgery Framed sterotactic biopsy

Sterotactic Surgery Frameless stereotactic biopsy Neuronavigation system

Mr. H, 60 yr, CA lung

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

P.. 36 yr

Mr.DK. 40 yr , CA stomach

P.S. 40 yr , Advanced CA lung

K, 52 yr

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

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

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

The End