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BRAIN METASTASES FREQUENCY The most common intracranial tumors among adults occurring up to 10 times as frequently as primary tumors The most frequent metastatic neurologic complication of systemic cancer - 20-40% of adult cancer patients - 6-10% of pediatric group patients PATHOPHYSIOLOGY The most common metastases – intraparenchymal (may also involve the cranial nerves, the blood vessels (including the dural sinuses), the dura, the leptomeninges, the inner table of the skull) 80% cerebral hemispheres 15% cerebellum 5% brain stem * Single (1/4-1/3 of patients; colon, breast, renal cell carcinoma) or multiple (malignant melanoma, lung cancer) PRIMARY TUMOR TYPES Lung Breast Melanoma Colon Other known primary Unknown primary 48% 15% 9% 5% 13% 11% Patients less than 21 years old – mainly sarcomas (osteogenic sarcoma, rhabdomyosarcoma, Ewing’s sarcoma) and germ cell tumors CLINICAL MANIFESTATION > 80% of brain metastases are discovered after the diagnosis of systemic cancer Progressive neurologic dysfunction is related to the gradually expanding tumor mass, associated edema or to the development of obstructive hydrocephalus. A more acute onset may occur after a seizure, a hemorrhage into a metastasis, an invasion or compression of an artery by tumor, or a stroke caused by embolization of tumor cells. SYMPTOMS * Headache (42%) – more common in patients with multiple metastases in the posterior fossa; may become more intense with postural changes or straining; may be associated with other symptoms of increased intracranial pressure – vomiting, vissual blurring, confusion, syncope • Focal weakness (27%) Mental change (31%) – memory problems, mood or personality • changes, cognitive dysfunction Seizure – usually focal or secondary generalized after a focal onset • • • • Gait ataxia Sensory disturbance Speech problems SIGNS Altered mental status Hemiparesis Hemisensory loss Papilledema Gait ataxia Aphasia Visual field cut Depressed level of consciousness DIAGNOSIS Contrast enhanced MRI - presence of multiple lesions - gray-white junction location - lesser degree of margin irregularity - associated vasogenic edema (not all metastatic tumors) ** enables to differentiate among other conditions (primary brain tumors, abscesses, cerebral infarcts, hemorrhages, demyelinating disease) • CT • Searching for primary focus (chest radiographs, CT or MRI of the abdomen) TREATMENT Corticosteroids (dexamethasone) Surgery Radiotherapy Radiosurgery Brachytherapy Chemotherapy SURGERY Therapeutic and diagnostic Surgical considerations are based mainly on accessibility and resectability * superiority of surgery and whole-brain rth to whole-brain rth alone in survival, local tumor control and neurologic performance! SURGERY Prognostic factors: - status of systemic disease - extent of neurologic deficit - time between the first diagnosis of cancer and the diagnosis of brain metastasis - location of the lesion - type of primary tumor * 31-48% of surgically treated patients experience recurrence in the brain SURGERY - COMPLICATIONS Herniation due to edema and increased intracranial pressure Hemorrhage Uncontrolled systemic cancer Thromboembolic phenomena (pulmonary embolism) Hematomas Wound infection Surgery-induced neurologic impairment RADIOTHERAPY Remains an important treatment modality When used promptly can reverse neurologic deficits Postoperative whole-brain rth reduces the local recurrence rate New techniques: - radiosurgery (external irradiation that uses stereotactically directed beams to deliver a high single dose of radiation to a small volume) - brachytherapy WHOLE-BRAIN RTH – LATE COMPLICATIONS • • • • Brain atrophy Necrosis Endocrine dysfunction Leukoencephalopathy with neurocognitive deterioration * the incidence of late complications is related to: total dose, fraction size, performance status, extent of CNS disease, preexisting neurologic impairment, concurrent chemotherapy