Brain Metastases and Neoplastic Meningitis
Summary of Key Points
Epidemiology
• Central nervous system metastases are common, affecting as many as 25% of patients with cancer.
• Most central nervous metastases involve the brain.
• Less often, the dura, leptomeninges, skull base, or cranial nerves may be affected.
• The terms “neoplastic meningitis” and “carcinomatous meningitis” refer to the dissemination of cancer cells within the leptomeningeal space.
• The most frequent primary tumor types that give rise to brain metastases include lung cancer, melanoma, breast cancer, and renal cell carcinoma.
Diagnosis
• Brain metastases are best detected with contrast-enhanced magnetic resonance imaging.
• Metastases generally appear as enhancing, well-circumscribed lesions with or without surrounding vasogenic edema.
• Biopsy or resection may be indicated to confirm the diagnosis, particularly in a patient with a single lesion and no cancer diagnosis or no known metastatic disease.
• Neoplastic meningitis often eludes early detection; meningeal enhancement is only visible on magnetic resonance imaging in about 50% of cases, and cerebral spinal fluid cytology may be negative initially in 40% to 50% of cases.
Treatment
• The most standard treatment for brain metastases is whole-brain radiotherapy (WBRT).
• Patients with a good prognosis and a limited number of brain metastases may benefit from more aggressive therapy such as surgery (especially for a single brain metastasis) or stereotactic radiosurgery (SRS), with or without adjuvant WBRT.
• After WBRT alone, the following observations have been made:
At least 60% of symptomatic patients improve significantly.
Median survival time is typically 3 to 6 months.
One-year actuarial local control probability may be as low as 14% or as high as 71%.
• Among patients with newly diagnosed brain metastases selected for surgery or SRS with or without WBRT, the following observations have been made:
Median survival time is approximately 9 to 11 months.
One-year actuarial local control rates are approximately:
There is increasing interest in combining systemic agents with radiation therapy.
• Intrathecal chemotherapy plays a major role in the management of neoplastic meningitis, alone or in combination with radiotherapy.
• Craniospinal radiotherapy causes significant acute toxicity and long-lasting myelosuppression.
• Accordingly, neoplastic meningitis may be managed with use of intrathecal chemotherapy combined with more limited radiotherapy.
1. In the randomized trial of surgical resection of a single brain metastasis followed by whole-brain radiotherapy (WBRT) versus observation reported by Patchell et al., which of the following end points was significantly improved in the WBRT arm?
B Karnofsky performance status at 6 months
C Steroid requirement at 6 months
2. In a large radiosurgery series for brain metastases, which pairs of percentages below best describe the local control rate and necrosis risk?
A Local control 70%; necrosis risk 5%
B Local control 70%; necrosis risk 15%
C Local control 80%; necrosis risk 15%
3. In the Radiation Therapy Oncology Group randomized trial of WBRT ± stereotactic radiosurgery (SRS) reported by Andrews et al., which end point was not significantly improved in the SRS arm (except on subset analysis)?
A Local control of brain metastases
B Karnofsky performance status at 6 months
4. In the Japanese randomized trial of SRS ± WBRT reported by Aoyama et al., which of the following end points was significantly worse in the SRS-alone arm?
1. Answer: A. Intracranial control was significantly improved in the WBRT arm, with less risk of local failure (10% for WBRT vs. 46% for observation), distant brain failure (14% vs. 37%), and any brain failure (18% vs 70%; P < .001). However, duration of functional independence was similar for the WBRT versus observation arms (37 weeks [8.5 months] vs. 35 weeks [8.0 months], respectively), as was survival time (48 weeks [11.0 months] vs. 43 weeks [9.9 months]; P = .39). Karnofsky performance status and steroid requirement at 6 months were not end points of this trial.
2. Answer: D. See Table 50-4. Representative references include References 91 and 95.
3. Answer: D. Survival was not significantly improved overall (5.7 months for WBRT vs. 6.5 months for WBRT + SRS; P = .136), although survival time was longer in the SRS arm among patients with a single brain metastasis (4.9 months for WBRT vs. 6.5 months for WBRT + SRS; P = .039). The following end points were all significantly better in the SRS arm: local control (P = .013), Karnofsky performance status at 6 months (P = .033), and steroid requirement at 6 months (P = .016).
4. Answer: A. Significantly poorer intracranial control was found in the SRS-alone arm (with 1-year brain freedom from progression probabilities of 24% for SRS alone vs. 53% for SRS + WBRT; P < .001) and more frequent brain salvage therapy (29 SRS-alone patients vs. 10 SRS + WBRT patients). The two arms had an equivalent 1-year neurologic preservation rate (70% for SRS alone vs. 72% for SRS + WBRT; P = .99), 1-year functional independent survival (27% vs. 34%; P = .53), and overall survival time (8.0 vs. 7.5 months; P = .42). Leukoencephalopathy occurred in two SRS-alone patients versus seven SRS + WBRT patients.
