Metastasis to the Central Nervous System

Abstract

Purpose of review: Management of metastasis to the central nervous system (CNS) has evolved, and molecular characterization of metastatic disease is now routinely done. Targeted therapies, once few in number with limited penetration into the CNS, have multiplied in number and increased in CNS coverage. This article addresses recent advances in the evaluation and clinical management of patients with CNS metastasis.

Recent findings: Metastasis of cancer to the CNS can be diagnosed and characterized with novel techniques, including molecular analyses of the spinal fluid, so-called liquid biopsies. Resected parenchymal CNS metastases are now routinely subjected to genomic sequencing. For patients with CNS metastases displaying targetable mutations, a wide variety of treatment options are available, including deferral of radiation therapy in favor of a trial of an orally bioavailable targeted therapy or immunotherapy. For patients without a molecularly targetable lesion, local treatment in the form of radiation therapy, now most often stereotactic radiosurgery, is supplanting untargeted whole-brain radiation therapy.

Summary: Technologic advances in diagnosis and management have resulted in new diagnostic and therapeutic approaches to patients with metastasis to the CNS, with resulting improvements in progression-free and overall survival.

FIGURE 6-1

Radiographic appearance of parenchymal brain metastasis in a 47-year-old woman with non–small cell lung cancer. A, Axial postcontrast T1-weighted MRI shows a round contrast-enhancing mass located at the gray-white junction. B, Axial fluid-attenuated inversion recovery (FLAIR) sequence shows edema surrounding the mass.

FIGURE 6-2

Radiographic appearance of leptomeningeal metastases in a 52-year-old man with non–small cell lung cancer. A, Axial postcontrast T1-weighted MRI shows linear enhancing plaques of disease (arrows) over the cerebellar folia. B, Axial postcontrast T1-weighted MRI shows patchy enhancement (arrows) of the cauda equina with clumping of nerve roots. C, Sagittal postcontrast T1-weighted MRI shows enhancement (arrows) along the length of the spinal cord surface and lumbar roots.

FIGURE 6-3

Imaging of the patient in CASE 6-1. Axial postcontrast T1-weighted MRIs show subcentimeter enhancing lesions at initial staging (A), radiographic response after initial treatment with pemetrexed and gemcitabine (B), recurrent disease after treatment with alectinib (C), and improvement of the largest metastasis and resolution of smaller metastases after treatment with lorlatinib (D).

FIGURE 6-4

Images of the patient presented in CASE 6-2. Initial axial postcontrast T1-weighted (A)and fluid-attenuated inversion recovery (FLAIR) (B) MRIs show a single parenchymal brain metastasis with abundant surrounding vasogenic edema. C, Axial postcontrast MRI attwo months after treatment with stereotactic radiosurgery. New contrast enhancement is apparent (arrow). D, Axial brain positron emission tomography (PET) shows hypometabolism (arrow) at the sites of T1-enhancing disease, consistent with radiation necrosis. E, Sagittal postcontrast T1-weighted MRI shows linear contrast-enhancing deposits over the cerebellar folia and pons. F, Sagittal postcontrast T1-weighted MRI shows resolution of the enhancing deposits after whole-brain radiation therapy and carboplatin.