Brain Metastases The Role of Surgery

Dr Orazio ArenaDirettore U.O. Neurochirurgia

Ospedale A.ManzoniLecco

Brain Metastases

• Are the most common brain tumors seen clinically; 10 times more common than primary brain tumors

• Annual Incidence of metastatic tumors:• 4-11 new cases /100 000 / year.

• 9/10 are intracranial metastases and 1/10 are intra-spinal metastases

• Autopsy studies have revealed the presence of intracranial metastases in 24% and intraspinal metastases in 5% of cancer patients

Voohies RM 1980, Fogelholm R 1984, Patchell RA 1985, Shaffrey ME 2004, Brem SN 2009, Mongan JP 2009.

Brain metastases

Primary Tumor site % of brain mets

Lung 50%

Breast 15%

Skin (Melanoma) 10.5%

Unknown primary site 11%

Delattre JY 1988, Posner JB 1995, Silverberg SG 1992, Norden AD 2005,Brem SN 2009

Brain metastases

Propensity to metastasize

• Melanoma 50%

• Lung carcinoma 25%

• Brest Carcinoma 25%

• Renal cell carcinoma 15%

• Colon carcinoma 5%

Brain Metastases

• Melanoma and Lung tend to have multiple brain lesions

• Breast, Colon and Renal cell carcinoma tend to present a single brain metastasis

• The interval between the diagnosis of the primary cancer and brain metastases depends on histology of the primary cancer: Breast cancer (longer) 3 years, Lung (shorter) 4-10 months.

Delattre JY 1988, Byrne TN 1983, Madajewicz S 1984,

Black P 2000

Multiple Brain Metastases (diagnosis)

• > 60% with MRI

• 40-50% with CT

Surgical Treatment Goal

• To relieve symptoms

• To provide long term local control

• To confirm histological diagnosis (through surgery only)

Surgical techniques

• Total removal

• «En bloc» resection (when feasible)

• Microsurgery

• Intraoperative image guidance (Neuronavigation,

Ultrasound, iMRI)

• Intraoperative neuromonitoring (SEP, MEP,

Cortical stimulation, Awake surgery)

Surgery vs SRS

Surgical patients selection

1. Clinical status (expected survival time)

2. Number of lesions

3. Size

4. Location

5. Histology of primary tumor (radiosensitivity)

• RPA classification system (class I-III) takes into account KPS, primary tumor control, age, extracranial spread

• Graded Prognostic Assesment GPA (score 0-4) takes into account number of metastasis

• Disease Specific-GPA takes into account primary tumor type

Clinical status

Clinical status

Unfavorable prognostic factors in brain metastases

• KPS <70

• Uncontrolled primary tumor

• Age >65 yrs

• Presence of systemic metastases

Clinical status Karnofsky Scale

Number of metastases

Single brain metastases are the best candidates for surgery

«Significant overall survival and functional indipendence advantage in the surgery + WBRT group vs. WBRT group» (Class I evidence)

(indipendent favorable predictive factors are total removal and increased interval between diagnosis of primary tumor and metastasis)

Patchell RA et al. 1990 N Engl J Med 322(8):494-500

Vecht CJ et al. 1993 Ann Neurol 33 (6):583-90

Number of metastases

Presence of Multiple Brain Metastasesgenerally is a surgical contraindication

No difference in mortality-morbility between single or multiple resection and no difference in overall survival if :

number of brain lesions = o <3,

age < 60y,

KPS >70,

complete surgical resection (Class III evidence)

Bindal RK, 1993

“In presence of multiple lesions, if one dominant lesion causing mass effect is life threatening or reduces the quality of life resection of the dominant lesion is preferable”

Sawaya R Intracranial Metastases Current Management Strategies, 2008

Number of metastases

Size of brain metastasis

• For single lesion greater than 3 cm in maximum diameter surgery is the first therapeutic option

• For single lesion with diameter < 1cm SRS is the first therapeutic option.

• For single lesion with diameter 1-3 cm surgical indication is debatable (surgery vs. SRS )

Bindal RK 1993, Sawaya R 1998, Patchel RA 1998, Iwadate Y 2000, Muller R 2009

Location of brain metastasis

The brain metastases are localized in the arterial border zones and in the junction between cortex and white matter

Usually they have a hematogenous diffusion;local extension can also occur:

• 80% cerebral hemispheres• 15% cerebellum• 5% basal ganglia, thalamus and brain stem

Delattre JY 1988, Posner JB 1995, Shaffrey ME 2004, Brem SN 2009, Mongan JP 2009.

Location of brain metastasis

• Surgical mortality-morbidity depends principally by the tumor location.

• Also complete tumor removing depends principally by the tumor location (superficial/deep , eloquent/near eloquent area)

• Non surgical candidate: brain stem, thalamus and basal ganglia lesions

Bindal RK 1993, Vecht CJ 1993, Sawaya R 1998,

Patchel RA 1998, Iwadate Y 2000, Muller R 2009

Histology of primary tumor

Brain metastases with high radiosensitivity are not candidated for surgery (Lang FF 1996, Brown PD 2002 )

High sensitivity

Intermediate sensitivity

Poor sensitivity

Lymphoma Breast Melanoma

Germinoma Lung (non small cell)

Kidney

Lung ( Small cell) Colon Sarcoma

Other factors evaluated in surgical decision-making

• Marked peritumoral edema

• Hydrocephalus

• Cystic or necrotic lesion

• Neurological syndrome (reversibility)

• Diagnostic uncertainty

• Failure of previous radiotherapy

• Leptomeningeal spread

Hypernephroma L F metastasis (surgery)

Lung adenocarcinoma L T-P metastasis (surgery)

Hypernephroma L F metastasis (surgery)

Lung spino-cellular carcinoma L T-O metastasis (surgery)

Lung adenocarcinoma R T metastasis (surgery)

Lung adenocarcinoma R prerolandic metastasis (surgery)

Lung adenocarcinoma R T metastasis (surgery)

Breast carcinoma L parasagittal metastasis (surgery)

Breast carcinoma

Double cerebellar metastases (surgery)

Melanoma Multiple metastases (surgery)

Lung adenocarcinoma Brainstem metastasis (SRS)

Breast carcinoma L parietal metastasis (SRS)

Lung adenocarcinoma Mid-Callosal metastasis (SRS)

Breast carcinoma R T-polar metastasis (SRS)

Our recent surgical series (2009-2014) 83 cases

• 38/83 lung cancer (46%)

• 18/83 breast cancer (22%)

• 14/83 melanoma (16%)

• 8/83 colonrectal cancer (10%)

• 5/83 kidney cancer (6%)

Our recent surgical series (2009-2014) 83 cases

• In 76 of 83 cases removal of a single metastasis (in 7of 83 multiple metastases )

• In only 3 cases total removal of multiple metastases ( single procedure)

• 6 of 8 members of the surgical staff involved as first surgeon

• Routine use of microneurosurgery and neuronavigation ( no IONM; no iMRI)

• 1 death from PE

• 1 moderate hemiparesis

• 2 transient neurological dysfunctions (aphasia, confusional state)

• 1 deep infection (successful re-operation)

• 4 reversible general complications (pneumonia, PE, flebothrombosis, sepsis)

Mortality-Permanent morbidity < 3%

Surgical complications ( within 30 days )

in 83 cases

5-year and median ST in our 10–year surgical series (119 cases from 2005 to 2014)

• Breast 23,8 % 29m

• Lung 21,4% 10m

• Kidney 20 % 28m

• Skin 9,3% 5m

• Colon 0 % 5m

Conclusions

• The surgical procedure for single metastases is easy and has very low morbidity

• In our surgical series there is a significative percentage of patients with a long (>5 years) survival after surgery, in the order of 20%

• The key to success of this surgery lies in the correct selection of patients, on the basis of a multidisciplinary assessment; the respective roles of surgery and SRS must be better defined