- Primary Intracranial Tumors
- Astrocytomas Including Glioblastomas
- Oligodendrogliomas
- Ependymomas
- Primary CNS Lymphomas
- Medulloblastomas
- Meningiomas
- Schwannomas
- Tumors Metastatic to the Nervous System
- Leptomeningeal Metastases
- Spinal Cord Compression from Metastases
- Complications of Radiation Therapy
| APPROACH TO THE PATIENT | ||
Tumors of the Nervous SystemClinical PresentationBrain tumors can present with general and/or focal symptoms and signs. Nonspecific symptoms include headache with or without nausea and vomiting, cognitive difficulties, personality change, and gait disorder. The classic brain tumor headache predominates in the morning and improves during the day, but this pattern is seen only in a minority of pts. Papilledema may suggest elevated intracranial pressure. Focal symptoms and signs include hemiparesis, aphasia, or visual field deficit; these are typically subacute and progressive. Seizures are common, occurring in ∼25% of pts with brain metastases or malignant glioma, and are the presenting symptom in up to 90% of pts with low-grade glioma. EvaluationPrimary brain tumors, unlike metastases, have no serologic features of malignancy such as an elevated ESR or tumor-specific antigens. Cranial MRI with contrast is the preferred diagnostic test for any pt suspected of having a brain tumor; CT should be reserved for pts unable to undergo MRI. Malignant brain tumors typically enhance with contrast and may have central areas of necrosis; they are characteristically surrounded by edema of the neighboring white matter. Low-grade gliomas typically do not enhance. Meningiomas have a typical appearance on MRI because they are dural-based enhancing tumors with a dural tail that compress but do not invade the brain. Additional testing such as cerebral angiogram, EEG, or lumbar puncture is rarely indicated or helpful. |
| TREATMENT | ||
Tumors of the Nervous SystemSYMPTOMATIC TREATMENT
DEFINITIVE TREATMENT
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Astrocytomas Including Glioblastomas 
Infiltrative tumors with a presumptive glial cell of origin. Most common primary intracranial neoplasm. Only known risk factors are ionizing radiation, uncommon hereditary syndromes (neurofibromatosis, tuberous sclerosis), and immunosuppression (primary CNS lymphoma). Infiltration along white matter pathways often prevents total resection. Imaging studies (Fig. 75-1. Postgadolinium T1 MRI of a Large Cystic Left Frontal Glioblastoma) fail to indicate full tumor extent. Grade I tumors (pilocytic astrocytomas) are the most common tumor of childhood, typically in the cerebellum; can be cured if completely resected. Grade II astrocytomas usually present with seizures in young adults; if feasible should be surgically resected. In pts at higher risk for recurrence (subtotal resection or above the age of 40 years), radiation therapy (RT) followed by PCV (procarbazine, (cyclohexylchloroethylnitrosourea [CCNU]), and vincristine) chemotherapy may possibly be of benefit. The tumor transforms to a malignant astrocytoma in most pts, leading to variable survival with a median of about 5-10 years. Grade III (anaplastic astrocytoma) and grade IV (glioblastoma) astrocytomas are treated similarly with maximal safe surgical resection followed by RT with concomitant temozolomide, followed by 6-12 months of adjuvant temozolomide. With this regimen, median survival is increased to 14.6-18 months compared to only 12 months with RT alone, and 5-year survival is approximately 10%. Despite optimal therapy, glioblastomas invariably recur. Treatment options for recurrent disease may include reoperation, carmustine wafers, and alternate chemotherapeutic regimens. Reirradiation is rarely helpful. Bevacizumab, a humanized vascular endothelial growth factor (VEGF) monoclonal antibody, increases progression-free survival but not overall survival.
Generally more responsive to therapy and have a better prognosis than pure astrocytic tumors. Usually nonenhancing; often partially calcified. Treated with surgery and, in pts with residual disease or above the age of 40 years, RT and chemotherapy. Median survival in excess of 10 years.
Derived from ependymal cells; highly cellular. Location-spinal canal more than intracranial in adults. If total excision possible, may be curable. Partially resected tumors will recur and require irradiation.
B-cell malignancy; many occur in immunosuppressed pts (organ transplantation, HIV) and Epstein-Barr virus (EBV) plays an important role in this population. Incidence is increasing, particularly in immunocompetent, older individuals. May present as a single mass lesion (more common in immunocompetent pts) or as multiple mass lesions or meningeal disease. Ocular and leptomeningeal involvement each occur in 15-20% of pts. Dramatic, transient responses occur with glucocorticoids; therefore, whenever possible, glucocorticoids should be withheld until after biopsy obtained. Pts should be tested for HIV and extent of disease assessed by positron emission tomography (PET) or CT of the body, MRI of spine, CSF analysis, and slit-lamp examination of the eye. In immunocompetent pts, high-dose methotrexate produces median survival up to 50 months. Addition of cytarabine increases the response rate, and the anti-CD20 monoclonal antibody rituximab is often incorporated into the regimen. Whole-brain RT prolongs progression-free survival but not overall survival. In immunocompromised pts, prognosis is worse and treatment is with high-dose methotrexate-based regimens and, in HIV, antiretroviral therapy; whole-brain RT is reserved for pts who can't tolerate systemic chemotherapy.
Most common malignant brain tumor of childhood. Half in posterior fossa; highly cellular; derived from neural precursor cells. Treatment with surgery, RT, and chemotherapy. Approximately 70% of pts have long-term survival, but usually at the cost of significant neurocognitive impairment.
The most common primary brain tumor. Extra-axial mass attached to dura; dense and uniform contrast enhancement is diagnostic (Fig. 75-2. Postgadolinium T1 MRI Demonstrating Multiple Meningiomas along the Falx and Left Parietal Cortex). Total surgical resection of large, symptomatic benign meningiomas is curative. With subtotal resection, local RT reduces recurrence. Small, asymptomatic meningiomas may be followed radiologically without surgery. Treat rare aggressive meningiomas with excision and RT or stereotactic radiosurgery (SRS).
Vestibular schwannomas present as progressive, unexplained unilateral hearing loss. MRI reveals dense, uniformly enhancing tumor at the cerebellopontine angle. Surgical excision may preserve hearing.
Tumors Metastatic to the Nervous System
Hematogenous spread most common. Skull metastases rarely invade CNS; may compress adjacent brain or cranial nerves or obstruct intracranial venous sinuses. Primary tumors that commonly metastasize to the nervous system are listed in Table 75-1 Frequency of Nervous System Metastases by Common Primary Tumors. Brain metastases are well demarcated by MRI and enhance in a ring pattern or diffusely. The radiographic appearance is nonspecific; similar-appearing lesions can occur with infection including brain abscesses, demyelinating lesions, sarcoidosis, radiation necrosis, or a primary brain tumor that is a second malignancy in a pt with systemic cancer. Biopsy rarely necessary for diagnosis because imaging alone in the appropriate clinical situation usually suffices. However, in approximately 10% of pts, a systemic cancer may present with brain metastases; in this situation biopsy of primary tumor or accessible brain metastasis is needed to plan treatment. Brain metastases are single in approximately one-half of pts and multiple in the other half. Treatment is with glucocorticoids, RT, or surgery. Standard treatment has previously been whole-brain RT; approximately 80% of pts improve with glucocorticoids and RT, but it is not curative, is associated with neurocognitive toxicity, and produces median survival of only 4-6 months. If feasible, SRS (gamma knife, linear accelerator, proton beam, or CyberKnife) has become the primary radiation oncology approach to brain metastases. It can sterilize visible lesions and produce local disease control in 80-90% of pts. SRS can effectively treat up to 10 lesions; it is, however, confined to lesions of ≤3 cm and is most effective in metastases of ≤1 cm.
Surgical excision of a single metastasis, or sometimes two lesions, followed by whole-brain RT is another option. Systemic chemotherapy may produce dramatic responses in highly chemosensitive tumor types such as germ cell tumors or small-cell lung cancer harboring specific epidermal growth factor receptor (EGFR) mutations that sensitize them to EGFR inhibitors. Immunotherapy can also be effective against primary tumors that are sensitive to this approach, such as melanoma.
Also described as carcinomatous meningitis, meningeal carcinomatosis, or in the case of specific tumors, leukemic or lymphomatous meningitis. Presents as headache, encephalopathy, cranial nerve, or polyradicular symptoms. Diagnosis by CSF cytology, MRI (nodular meningeal tumor deposits or diffuse meningeal enhancement), or meningeal biopsy. Associated with hydrocephalus due to CSF pathway obstruction. Treatment is palliative, often with RT to the symptomatically involved areas, or chemotherapy (systemic or intrathecal).
Spinal Cord Compression from Metastases
(See Chap. 22 Spinal Cord Compression). Expansion of vertebral body metastasis posteriorly into epidural space compresses spinal cord or cauda equina. Most common primary tumors are breast, lung, prostate, kidney, lymphoma, and myeloma. Back pain (>90%) precedes development of weakness, sensory level, or incontinence. Medical emergency; early recognition of impending spinal cord compression essential to avoid devastating sequelae. Diagnosis is by MRI; imaging of the entire spine important to identify additional clinically silent lesions. Demonstration of tumor cells in the CSF is definitive; however, CSF cytology is positive in only 50% of pts on the first lumbar puncture and still misses 10% after three CSF samples. New technologies, such as rare cell capture, enhance identification of tumor cells in the CSF. Treatment is by surgical resection followed by RT. If surgery is not feasible, RT or SRS is the best option.
Complications of Radiation Therapy
Three patterns of radiation injury after CNS RT:
- Acute: headache, sleepiness, nausea and vomiting, worse neurologic deficits during or immediately after RT. Rarely seen with current protocols. Can be both prevented and treated with glucocorticoids.
- Early delayed: worsening or reappearance of a pre-existing neurologic deficit; within weeks to months of RT. Increased T2 signal and sometimes enhancement on MRI that can mimic tumor recurrence (“pseudoprogression”). Self-limited and improves with glucocorticoids; if very symptomatic may require resection. With spinal cord RT, Lhermitte sign with paraesthesias can occur; usually self-limited and benign.
- Late delayed: dementia or other progressive neurologic deficits; typically months to years after RT. White matter abnormalities on MRI (leukoencephalopathy) or ring-enhancing mass (radiation necrosis). PET can distinguish delayed necrosis from tumor recurrence as can MR perfusion sequences. Progressive radiation necrosis is best treated palliatively with surgical resection unless it can be managed with glucocorticoids. Radiation injury of large arteries accelerates the development of atherosclerosis, increasing the risk of stroke years after RT. Endocrine dysfunction due to hypothalamus or pituitary gland injury can be due to delayed effects of RT. Development of a second neoplasm after RT also is a risk many years after exposure.