5.1 Brain, Spinal Cord Tumors & Metastatic Patterns

Overview and Relevant Anatomy

The central nervous system (CNS) presents unique radiotherapy challenges because of its complex anatomy, densely packed radiosensitive substructures, and the influence of the blood-brain barrier on tumor biology and drug delivery. The brain is organized into the cerebrum (frontal, parietal, temporal, and occipital lobes), the cerebellum, the brainstem (midbrain, pons, and medulla oblongata), and the diencephalon (thalamus, hypothalamus, and pituitary gland). Three meningeal layers — dura mater, arachnoid mater, and pia mater — envelop the brain and spinal cord, and cerebrospinal fluid (CSF) circulates through the ventricular system and subarachnoid space, cushioning neural tissue and providing a pathway for tumor cell dissemination.

Primary CNS tumors arise from several cell lineages: glial cells produce astrocytomas, oligodendrogliomas, and glioblastoma multiforme (GBM); the meninges give rise to meningiomas; embryonal precursor cells in the cerebellum produce medulloblastoma, the most common malignant pediatric brain tumor; ependymal cells lining the ventricles produce ependymoma; and the sellar/pineal region produces pituitary adenomas, craniopharyngiomas, and germ cell tumors. GBM (WHO grade 4, typically IDH-wildtype) is the most common malignant primary brain tumor in adults. It infiltrates diffusely along white matter tracts, which is why gross total resection rarely achieves cure and postoperative radiotherapy with concurrent temozolomide is standard of care.

The spinal cord extends from the foramen magnum to roughly the L1-L2 vertebral level in adults, tapering into the conus medullaris and continuing as the cauda equina nerve roots. Intramedullary tumors (ependymoma, astrocytoma) arise within the cord itself, while extramedullary tumors (meningioma, schwannoma) and epidural metastatic disease compress the cord from outside. Metastatic epidural spinal cord compression (MESCC) is an oncologic emergency; delayed treatment risks permanent paraplegia, so same-day or next-day simulation and treatment initiation is often required.

Metastatic Patterns and CSF Spread

Brain metastases are dramatically more common than primary brain tumors, developing in an estimated 20-40% of adult cancer patients during their disease course. Lung cancer is the most frequent source of brain metastases, followed by breast cancer, melanoma, renal cell carcinoma, and colorectal cancer. Melanoma carries the highest per-lesion propensity to spread to the brain despite lung and breast cancers producing more absolute cases because those primaries are simply more prevalent overall. Hematogenous spread through the arterial circulation explains why metastases preferentially lodge at the gray-white matter junction: small-caliber vessels narrow abruptly at this boundary, trapping tumor emboli that then proliferate.

Leptomeningeal spread, also called carcinomatous meningitis, occurs when malignant cells seed the CSF and coat the pia-arachnoid surfaces of the brain and spinal cord. It is diagnosed through CSF cytology and MRI findings of linear or nodular leptomeningeal enhancement, and it is seen most often with breast cancer, lung cancer, melanoma, and hematologic malignancies such as leukemia and lymphoma. Because CSF bathes the entire neuraxis, malignant cells can travel freely from the ventricles down to the lumbar thecal sac, producing so-called drop metastases. This phenomenon is the direct rationale for craniospinal irradiation (CSI) in medulloblastoma and other tumors prone to CSF dissemination: CSI treats the whole brain and the entire spinal subarachnoid space, extending inferiorly to cover the thecal sac (typically to the S2-S3 level, confirmed on MRI), because imaging alone cannot reliably exclude microscopic seeding anywhere along that pathway.

Critical Organs at Risk and Therapist Considerations

Several radiosensitive structures dictate planning constraints and daily setup priorities:

• Optic chiasm and optic nerves: risk of radiation-induced optic neuropathy; conventional point-dose constraints are typically kept below roughly 54-55 Gy.
• Brainstem: tolerance is comparatively low, and overdose can cause severe, potentially fatal toxicity, so brainstem point-dose limits are enforced strictly, especially in posterior fossa and skull-base plans.
• Cochlea: sensorineural hearing loss is a long-term risk, particularly relevant in posterior fossa treatment and craniospinal irradiation for medulloblastoma.
• Lens: cataract formation is dose-dependent; lens dose is minimized whenever fields pass near the orbits.
• Hippocampus: implicated in memory and learning; hippocampal-avoidance whole-brain radiotherapy (HA-WBRT) has been shown to reduce neurocognitive decline in appropriately selected patients.
• Spinal cord: myelopathy risk is dose- and volume-dependent; cord constraints become especially critical in re-irradiation scenarios.

Treatment approach depends on disease extent and biology. Whole-brain radiotherapy (WBRT) treats multiple or diffuse metastases; stereotactic radiosurgery (SRS) delivers a highly conformal, ablative dose in one to five fractions for a limited number (roughly one to ten) of metastases, sparing normal brain through sharp dose fall-off; craniospinal irradiation covers the full neuraxis for medulloblastoma or other CSF-disseminating tumors; and fractionated conformal/IMRT plans for gliomas typically encompass the enhancing tumor plus surrounding T2/FLAIR signal abnormality with an additional margin to account for infiltrative disease.

From the therapist's perspective, rigid immobilization is paramount. Thermoplastic masks (often three- or five-point fixation) secure the head for fractionated treatment, while SRS frequently uses more rigid mask systems or stereotactic frames because sub-millimeter accuracy is required at the small treatment margins used. Daily image guidance -- cone-beam CT or optical surface tracking -- verifies position given the minimal planning target volume margins. For craniospinal irradiation, therapists must precisely match adjacent cranial and spinal fields, often using junction shifts partway through treatment, to avoid a cold or hot junction spot where fields abut along the spine.