Brain metastases Flashcards
What is the most common intracranial tumor?
Brain met is the most common intracranial tumor (outnumber primary brain tumors 8:1).
What is the annual incidence of brain mets in the United States?
170,000–200,000 cases/yr of brain mets in the United States, with development in up to 30% of pts with systemic cancer.
Why is the incidence of brain mets increasing?
The incidence is increasing due to advancements in systemic therapy (improved extracranial control) with limited penetration of the blood–brain barrier in conjunction with increased utilization of MRI/surveillance imaging.
What cancers are associated with hemorrhagic brain mets?
Hemorrhagic brain mets are most commonly associated with melanoma, RCC, and choriocarcinoma.
What do the terms solitary and single brain met connote?
A solitary brain met is only 1 brain lesion and no other sites of Dz progression.
A single brain met is only 1 brain lesion in addition to other sites of met Dz.
What cancers are most likely to metastasize to the brain?
Cancers associated with brain mets: lung (40%–50%), breast (15%), melanoma (10%)
In what % of pts are brain mets the 1st manifestation of Dz?
5%–20% of pts present with brain mets from an unknown primary. Pts presenting with brain mets without a prior Dx of cancer most often have a
lung primary.
Should Bx or resection be recommended if a new Dx of brain mets is suspected?
Yes. Bx should be considered in pts with a new Dx of brain mets as 11% of pts (6/54) enrolled in the 1st Patchell trial were found to have a primary brain tumor (3 pts) or inflammatory/infectious process (3 pts) despite MRI or CT
findings consistent with metastatic Dz. (Patchell R et al., NEJM 1990)
What is the more common type of brain mets: single or multiple?
Most pts have multiple brain mets rather than a single lesion, with increased detection of small, multifocal lesions on MRI typically not appreciated on
CT.
How do pts with brain mets present?
Presentation of pts with brain mets: Sx of ↑ ICP (HA, n/v), weakness, change in sensation, mental status changes, and seizure
What is carcinomatous meningitis?
Carcinomatous meningitis is a clinical syndrome caused by leptomeningeal met with widespread involvement of the cerebral cortex. The Dx is associated with a poor prognosis.
Where do most brain mets occur?
Most brain mets arise in the gray/white matter junction due to hematogenous dissemination with narrowing of blood vessels. (Delattre J et al., Arch Neurol 1988)
Are most brain mets infra- or supratentorial?
The majority of brain mets are supratentorial.
What is the distribution of brain mets within the brain?
The distribution of brain mets correlates with relative weight and blood flow:
Cerebral hemispheres: 80%
Cerebellum: 15%
Brainstem: 5%
What is the overall median time from initial cancer Dx to development of brain mets?
The median overall time from initial cancer Dx to development of brain mets is 1 yr.
Do most pts with brain mets die from their CNS Dz?
No. ∼30%–50% of pts with brain mets die from their CNS Dz.
Describe the workup of a brain met.
Brain met workup: H&P focus on characterization of any neurologic Sx, evaluation for infectious causes (fever, CBC), careful neurologic exam, MRI brain +/– gadolinium, assessment for status of extracranial Dz, determination
of KPS, and neurosurgery consult
What is the DDx for a new lesion in the brain?
Brain lesion DDx: mets, infection/abscess, hemorrhage, primary brain tumor, infarct, tumefactive demyelinating lesion, and RT necrosis
What imaging features are suggestive of brain mets?
Imaging features suggestive of brain mets include lesions at gray/white matter junction, multiple lesions, ring-enhancing lesions, and significant vasogenic edema
What is triple-dose gadolinium, and why is it used?
Triple-dose gadolinium: 0.3 mmol/kg. It is used to increase the sensitivity of MRI.
Describe the RTOG recursive partitioning analysis (RPA) classes for brain mets. (Gaspar L et al., IJROBP 1997)
1: ≥70 <65, Primary controlled, and no extracranial
mets
2: ≥70 Either age >65, Or primary uncontrolled
3: <70
What is the MS time for RTOG RPA classes I, II, and III?
Class I: 7.2 mos
Class II: 4.2 mos
Class III: 2.3 mos
What is the Sperduto Index?
The Sperduto Index is a graded prognostic assessment based on age, KPS, #of brain mets, and the presence or absence of extracranial mets developed from an analysis of 1,960 pts in the RTOG database. Criteria is based on a point system:
0 points: age >60 yrs, KPS <70, >3 brain mets, presence of extracranial mets
0.5 points: age 50–59 yrs, KPS 70–80, 2 CNS mets
1 point: age <50 yrs, KPS 90–100, 1 CNS met, no extracranial mets
The sum of points predicts MS in mos: 0–1 point: 2.6 mos 1.5–2.5 points: 3.8 mos 3 points: 6.9 mos 3.5–4 points: 11 mos
What is the Diagnosis Specific Graded Prognostic Assessment (DS-GPA)?
The DS-GPA is a graded prognostic assessment developed from a retrospective database of 4,259 eligible pts from 11 institutions with determination of significant prognostic factors based on the primary
histology. (Sperduto P et al., IJROBP 2010)
What are the significant prognostic factors?
Non-small cell lung cancer (NSCLC)/small cell lung
cancer: age, KPS, presence of extracranial mets and number of brain mets
Renal cell/melanoma: KPS and the number of brain mets
Breast/GI: KPS
In pts with untreated brain mets, what is the MS?
MS of untreated brain mets is 1 mo.
What Tx may be used for brain mets?
Brain met Tx: steroids, Sg, fractionated RT (WBRT), and SRS
In pts with brain mets treated with steroids alone, what is the MS?
MS in pts with brain mets treated with steroids alone is 2 mos.
What randomized data investigated pt survival or QOL with the addition of WBRT to best supportive care?
The completed MRC Quartz trial was a randomized, noninferiority phase III trial investigating the role of optimal supportive care (OSC) + WBRT (4 Gy
× 5 fx) vs. OSC alone in pts with inoperable brain mets from NSCLC. The primary outcome measure was quality-adjusted life yrs (QALY). The trial did
not show a difference in QALY with the addition of WBRT to OSC—though conclusions related to the specific population examined in the trial. (Mulvenna P et al., Lancet 2016)
What are some criticisms of the QUARTZ trial?
Potential bias toward enrollment of pts with poor PS (40% with KPS <70), and perceived shorter life expectancy, as MS was ∼2 mos compared to
historical WBRT trials of ∼4 months. Additionally, the WBRT dose/fractionation scheme is not routinely used in pts with perceived longer life expectancy, also suggesting there may have been a bias toward pts with
shorter life expectancy/poor PS.