Pocket Oncology (Pocket Notebook Series), 1st Ed.

CNS METASTATIC DISEASE

Connie Lee Batlevi and Thomas J. Kaley

Epidemiology

• 8–10% CA pts w/sx met to brain

• Most commonly a/w lung (20%), melanoma (7%), renal (7%), breast (5%), colorectal (2%), & CUP (JCO 2004;22:2865)

Clinical Manifestations and Diagnosis

• 80% cerebral hemispheres, 15% cerebellum, 5% brainstem (Oncologist 2007;12:884)

• Hematogenous spread to gray-white jxn where narrow blood vessels trap tumor emboli

• HA 24–53%, focal weakness 16–40%, altered mental status 24–31%, seizures 15%, ataxia 9–20%

• MRI more sensitive than CT. MRI ± = gold standard, w/good delineation of tumors. High-grade lesions & leptomeningeal met enhance, lower grade lesions (eg, glioma) typically do not. Limited by claustrophobia, metallic artifacts, pt w/implantable devices. CT ± w/less resolution compared to MRI esp in posterior fossa.

• Other imaging modalities: MR spectroscopy (measure metabolites), MR perfusion (measure cerebral blood flow), Brain FDG-PET (measure radiolabeled tracer) may help differentiate radiation necrosis from active tumor

• Size, number, & location of lesions, along w/amount of edema, PS & status of systemic illness guide decision to resect vs. stereotactic radiation (JNCCN 2008;6:505)

Prognosis

• RTOG retrospective recursive partitioning analysis: RPA Class I: <65 y, KPS >70%, controlled 1°, no extracranial met → median survival 7.1 mo; RPA Class II: Median survival 4.2 mo; RPA Class III:KPS < 70% → median survival 2.3 mo (Int J Radiat Oncol Biol Phys 1997;37:745).

• GPA scores based on age, KPS, number of CNS met, extracranial met. Low score = poor risk w/median survival ∼3–4 mos, intermediate score w/median survival 4–7 mos, high score w/median survival 11–25 mos. Updated w/disease-specific scoring system (JCO 2012;30:419).

Management

Sx control

• Corticosteroids—Lowest dose for shortest time. MSKCC typically starts at Decadron 8 mg q8h. Extensive mass effect should be premedicated w/steroids for 24 h prior to XRT.

• Antiepileptics—Seizure Ppx not routinely recommended in Asymtomatic pt. Recommend use of non-CYP450 inducing AED (levetiracetam, topiramate, valproic acid). Inducers of CYP450 medications (phenytoin, phenobarbital, carbamazepine) may be needed if status epilepticus.

Definitive tx

• One surgically accessible brain met—surgery + WBRT. Fewer death from neurologic cause while OS similar. Adjuvant WBRT vs. focal RT still debated (JAMA 1998;280:1485)

• 1–3 brain met w/no h/o CA & no readily accessible alternate site should be biopsied in pt w/stable systemic disease consider SRS and/or WBRT to reduce incidence of cerebral relapse (JAMA 2006;295:2483)

• Multiple brain met: WBRT as 1o tx. Palliative neurosurgery (open or SRS) considered for life-threatening mass effect, hemorrhage or hydrocephalus

RT

• SRS: Local control rate 80–90%. Tx medically or surgically inoperable pts, eliminate need for craniotomy, treat multiple lesions. Limited by lack of tissue dx, size of tumor, inability to reduce cerebral edema. RTOG 90–05 rec max marginal doses of 15–24 Gy based on tumor volume (Radiat Oncol Biol Phys 2000;47:291)

• WBRT: ↓ risk of subsequent tumor recurrence compared w/SRS. NoΔ OS. Doses vary 20–40 Gy in 5–20 fractions. Standard regimen 30 Gy in 10 fractions or 37.5 Gy in 15 fractions. Poor KPS pts can be treated w/20 Gy in 5 fractions (Lancet 2004;363:1665)

Chemotherapy

• Systemic chemotherapy—rarely used as 1o Rx. Curative sys chemo in met disease: Lymphoma, germ cell tumors, GTN chemo usu used in conjunction w/RT. Tx as per regimens of 1o tumor (lymphoma w/high-dose MTX, breast w/capecitabine, CIS, etoposide, high-dose MTX, SCLC w/topotecan).

Follow-up: MRI q2–3 mos for 1 y then as clinically indicated

Salvage Rx

• Prev tx w/surgery: Surgery, SRS, WBXRT, or chemotherapy

• Prev tx w/WBRT or SRS: Consider further RT depending upon prior dose & location

Leptomeningeal Metastasis

• Multifocal seeding of leptomeninges w/tumor by hematogenous dissemination, lymphatic spread or direct extension

• 5% of pts w/CA (Ann Onc 2004;15:285)

• Most commonly a/w breast (35%), lung (25%), lymphoma (11%), leukemia (8%), GI (6%), melanoma (5%) (Neurology 2010;74:1449)

Clinical Manifestation & Dx

• Local injury to nerves traveling through spinal fluid—nerve palsies, weakness, paresthesias, pain

• Direct invasion into brain, spinal tissue or local blood supply deprivation—focal findings, seizures

• Obstruction of nl CSF flow—HA, ↑ cranial pressure, hydrocephalus

• Cognitive dysfunction—encephalopathy

• CSF cytology 50% positive w/malignant cells, 90% w/repeated CSF but 10% persistently negative CSF. LP contraindicated in pts w/coagulopathy, thrombocytopenia, bulky intracranial disease. CSF w/↑ protein, pleocytosis, ↓ glc

• MRI w/diffuse &/or nodular enhancement of leptomeninges or hydrocephalus w/o mass lesion

Tx

• Chemotherapy—organ-specific chemotherapy using drugs w/good CNS penetration. CSF flow scan helps determine use of intrathecal chemo

• Radiation—good risk pt tx w/involved field RT to bulky/sx sites in spine or WBRT in brain; poor risk group tx w/palliation/best supportive care vs. fractionated EBRT