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) Approximately 80% of brain metastases are located in the… Brain metastases may be single or multiple. Metastases from colon, breast (…) are often single, whereas malignant melanoma and lung cancer produce multiple cerebral lesions. Single metastases occurs in only one third to one fourth of patients with cerebral metastases.

PRIMARY TUMOR TYPES Lung 48% Breast 15% Melanoma 9% Colon 5% Other known primary 13% Unknown primary 11% Patients less than 21 years old – mainly sarcomas (osteogenic sarcoma, rhabdomyosarcoma, Ewing’s sarcoma) and germ cell tumors Among adults the most common sources of brain metastases are… Among patients less than 21 brain metastases arise most often from sarcomas 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 Headaches occur in approximately half of patients. The headaches are often mild, diffuse or bifrontal. However, when focal, the headache may be localized at the site of the lesion. Early morning headache , belived to be associated with increased intracranial pressure occurs in less than half of suffering from headache patients. In case of posterior fossa metastases, the headache is caused by increased intracranial pressure, as the result of brain edema or hydrocephalus that exerts traction of pain-sensitive structures such as the venous sinuses and the dura at the base or back of the skull.

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 CT - 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) Contrast enhanced MRI is more sensitive than enhanced CT scanning. Imaging findings(…)

TREATMENT Corticosteroids (dexamethasone) Surgery Radiotherapy Radiosurgery Brachytherapy Chemotherapy Corticosteroids should be used at the onset for all symptomatic patients. 16mg/day. Patients who are receiving whole-brain irradiation should receive steroids for at least 48 hours before treatment. Steroid tapering may begin during week 2 of rth.

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! Enables to obtain diagnostic tissue and confirm the diagnosis of metastases – imprtant because some patients with a clinical diagnosis of metastases may in fact have nonmetastatic lesions. ! Restricted to younger patients without evidence of extracranial disease progression.

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 Operative mortality is most often defined as death within 30 days of operation. Morbidity is defined as increased postoperative neurologic deficits. (max.5%)

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 The optimal radiation time, dose regimen has not been established. Postoperative rth destroy microscopic residual cancer cells at the site of resection and and at other locations in the brain if they exist.

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 The role of chemotherapy has not been clearly defined. Most patients do not die of their brain metastases. They usually experience effective palliation of neurologic symptoms and extension of life. Future advances in treatment techniques may lead to further increases in the efficacy of treatment for brain metastases.