Management of brain

metastases
Brain metastases (BM) - incidence
• Burden brain metastasis is
significant
• Literature
• 8.3-14.3 / 100.000 inhabitants
• 8.5 – 9.6% of all cancer patients
develop BM
• 85% cerebral
• 10-15% cerebellar
• 1-3% brainstem
In our department prevalence of BM was of…

• 2006 – 14,19% (n=22) (81% supratentorial)

• 2016 – 15,41% (n=38) (78% supratentorial)

BM – systemic disease
- large differences according to primary tumor as well as age, gender,
race, cancer stage, and age at cancer diagnosis.

Most common cancers that metastasize to the brain, but percentage

varies greatly.
lung
breast
has the highest propensity of all systemic malignant
melanoma tumors to metastasize to the brain
renal
Barnholtz-Sloan JS, Sloan AE, Davis FG, et al. Incidence proportions of
brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan
Detroit Cancer Surveillance System. J Clin Oncol. 2004;22(14):2865–
2872.5.
BM – new therapeutic challenges
• Modern oncologic systemic therapies alter natural disease history
• BBB turns CNS into a to sanctuary for metastasis hard to penetrate by systemic therapy
• Mostly seen in
• HER 2 breast cancer – trastuzumab
• melanoma – immune check point inhibitors
• ALK arranged NSCLC – crizotinib

National Comprehensive Cancer Network. NCCN Guidelines for Treatment of Cancer by

Site. 2016.
Brain MRI screening in the absence of neurological symptoms
- advanced melanoma
- NSCLC
- small cell lung cancer
Updates in the management of brain metastases.
Arvold ND1, Lee EQ1, Mehta MP1, Margolin K1, Alexander BM1
Neuro-Oncology 18(8), 1043–1065, 2016 doi:10.1093/neuonc/now127
BM - Diagnosis
• MRI is the gold standard of imaging
• Characters of BM evaluated
• Number
• Size
• Location
• Brain reaction – peritumoral edema
• + MRI in the context of systemic cancer is predictive
But
- There is evident that systemic therapies for cancer can lead to
high grade gliomas.
High-grade gliomas in patients with prior systemic malignancies.
Maluf FC1, DeAngelis LM, Raizer JJ, Abrey LE.
Cancer. 2002 Jun 15;94(12):3219-24.
BM- Peritumoral edema significant?

- No significant difference between edema produced by different types of

metastases
- No correlation between extent of edema and overall survival in surgically
treated cases
 BM –Types of lesions
- Single
- Multiple
- Enhancing / Non enhancing
- Cystic , Ring shaped
- With / without significant
peritumor edema
Differential diagnosis
• Abscess
• High grade glioma
• Demyelinating disease
• Thromboembolic stroke
 BM - Survival
• Historically BM had an overall prognosis
of <6 months
• Today most prominent is the Disease
Specific Graded Prognostic Assessment
(DS-GPA) (KPS, age, number of BM and
+/- molecular subtype -breast cancer)
• High DS-GPA score – survival on 1 to 2
years
• Low DS-GPA – survival of approximately 3
months

• Importance of systemic disease status –

92% of deaths (1-10 BM, <3cm KPS>70,
treated by GK) occurred from systemic
disease progression
Lancet Oncol. 2014 Apr;15(4):387-95. doi:
10.1016/S1470-2045(14)70061-0
BM - Treatment options
• The major weapons in the arsenal against brain metastases
• Whole-brain radiotherapy (WBRT),
• Surgical resection by open craniotomy,
• SRS

• Systemic chemotherapy is not very effective against the most

common types of primary tumors metastasizing to the brain, which
tend to be chemo resistant
 BM – Radiotherapy: WBRT, SRS, WBRT+SRS?
• Cornerstone of modern BM
treatment
• More aggressive modalities reserved
for high DS-GPA score patients
• WBRT monotherapy is no longer
recommended due to prolonged
fatigue, neurocognitive deficits and
increased rates of necrosis
• There is no survival decrement by
withholding WRBT after surgery or
SRS
• High rates of local control are
achieved by SRS
 BM – Radiotherapy: WBRT, SRS, WBRT+SRS?
• SRS+WBRT / SRS - better local control rates
for SRS+WBRT but significant more
cognitive decline and no direct impact on
survival
• SRS monotherapy recommended for 1-4
BM (less 3 cm)
Am J Clin Oncol. 2016 Aug;39(4):416-22
• There is clinical indication that SRS is useful
also in >5 BM
• There has not been any clear indication
that either WBRT or SRS on resection cavity
improve survival
Challenges
• Access to SRS is difficult with only one center in Romania
• WBRT is more available but it still takes on average more than 4
weeks to initiate treatment
• Patients tend to neglect their systemic oncologic disease with
increased incidence of patients with multiple metastasis and / or
large metastasis and limited survival resources.
Surgery – place of BM surgery

• Surgey is still the optimal treatment for patients with 1 BM with *

• Key treatment modality for lesions over 3 cm or bulky lesions* generating
neurologic symptoms,
• Key treatment in the case of BM with large peritumor edema providing
immediate removal of edema source and decrease of ICP
• Extremely important in cases with cerebral metastasis and no systemic
disease found
• No radiotherapy without histopathological sampling

*The role of surgical resection in the management of newly diagnosed brain metastases: a
systematic review and evidence-based clinical practice guideline.
J Neurooncol. 2010 Jan;96(1):33-43
BM – Indications for surgery
• Size: tumor > 3cm
• Location: all BM except basal ganglia, thalamus or brainstem
• Clinical status: good clinical outcome with prolonged postoperative
survival if clinical status >70 KPS
• Number – still a controversy
• Past: no more than 1
• Now: As many as technically feasible, as long as there are no additional risks
regarding postoperative newly induced morbidity
BM – Surgery aims
• Aim of surgery:
• Complete surgical resection
• Low morbidity
• Sustained local tumor control
• In order to achieve the surgical aims we need:
Adjuncts to surgery
• Neuronavigation
• Functional MRI – eloquent area surgery
 Surgical approach

Is decided by the location of BM and

number of BM operated on
Approach should provide at the same
time:
• easy access
• shortest intraparenchymal route
• avoid eloquent areas
• allow for complete tumor
resection without post surgery
morbidity
Surgical technique
• Extracapsular whole tumor resection– no spreading of metastatic tumor
cells
Possible if:
well delimited tumor
relatively small tumor
tumor not in or immediate vicinity of eloquent area

• Picemeal tumor resection

In the case of:
cystic lesions
large tumors
BM – How do I operate multiple BM
• 40 yo male
• 3 supratentorial BM
• NSCLC
• Good clinical condition
• One GM seisure
Posterior fossa BM
• video