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• Local tumor growth, edema, or both may cause focal neurologic dysfunction, increased intracranial pressure, and hydrocephalus. The neurologic effects of a locally growing or infiltrating tumor may be somewhat predicted by tumor location. With significant cerebral edema or hydrocephalus, signs and symptoms of increased intracranial pressure and generalized cerebral dysfunction may predominate.
• Increased intracranial pressure or local pressure on sensitive intracranial structures
(dura and vessels) may cause headaches, which usually are worse in the morning. Associated findings include focal neurologic deficits and papilledema.
• Long-standing increases in intracranial pressure may lead to optic atrophy and
blindness.
• Seizures are common and may be partial (simple, complex, secondarily generalized)
or generalized (tonic clonic, absence); the highest incidence is with low-grade neoplasms.
• Lumbar back pain or bowel or bladder dysfunction may suggest CSF metastasis in
lumbar cistern.
Diagnostic Workup
• The initial workup of patients with brain tumors must include a complete history and a
general physical examination (Table 15-1). Data obtained from relatives and friends are often more helpful than those given by the patient.
• Complete neurologic examination includes assessment of mental condition,
coordination, sensation, reflexes, and motor and cranial nerves.
• Ophthalmoscopy checks for papilledema as a sign of increased intracranial pressure.
• The most useful magnetic resonance imaging (MRI) studies are T1-weighted sagittal
images, gadolinium-enhanced and unenhanced T1 axial images, and T2-weighted axial images. T1 images better demonstrate anatomy and areas of contrast enhancement; T2 images are more sensitive for detecting edema and tumor. Computed tomography (CT) scans with contrast material also are useful.
• Staging of the neuraxis is essential for neoplasms at high risk of spread to the CSF.
Neuraxis imaging with myelography has largely been replaced with gadolinium- enhanced MRI of the spine. Ideally, neuraxis imaging should be done preoperatively to avoid surgical artifacts and false-positive scans. Spinal imaging usually is
combined with CSF cytology for complete neuraxis staging.
• Biopsy of any CNS tumor is strongly recommended, although primary CNS
lymphoma may be treated in selected cases without biopsy confirmation. Selected patients with imaging and symptoms consistent with low-grade glioma also may be followed without biopsy, although a tissue diagnosis is recommended.
• CSF cytology is essential for staging tumors with a propensity for CSF spread (e.g.,
germ cell tumor, primitive neuroectodermal tumor, medulloblastoma, CNS
lymphoma). CSF sampling in the immediate postoperative period may lead to false- positive studies and is best done either preoperatively or more than 3 weeks postoperatively.
Table 15-1: Diagnostic workup for tumors of brain, brainstem, and cerebellum
Clinical history
General physical examination Complete neurologic evaluation Imaging studies (one of the following)
Computed tomography scan of head with contrast material or
Magnetic resonance imaging with gadolinium Laboratory studies
Complete blood cell count, blood chemistry profile
Cerebrospinal fluid chemistry, cytology, microbiology studies, as indicated Biopsy
From Wara WM, Bauman GJ, Sneed PK, et al. Brain, brainstem, and cerebellum. In: Perez CA, Brady LW, eds. Principles and practice of radiation oncology, 3rd ed. Philadelphia:
Lippincott–Raven, 1998:777–828, with permission.
Staging Systems
• The American Joint Committee on Cancer (AJCC) has published a staging system for
brain tumors (Table 15-2) (2). However, in the fifth edition of the American Joint
Committee on Cancer (AJCC) Cancer Staging Manual, no formal staging was
recommended because of the lack of reliable prognostic factors in clinical trial outcomes (8). On the other hand, a recursive partitioning analysis by the Radiation Therapy Oncology Group (RTOG) showed that patients with brain gliomas grouped according to age, Karnofsky performance status, histology, mental status, and irradiation dose could be classified into six groups with regard to prognosis and response to treatment (30).
• Chang et al. (4) proposed a staging system for medulloblastoma.
Table 15-2: TMN staging of brain tumors
T Primary tumor
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Supratentorial tumor
T1 Tumor 5 cm or less in greatest dimension; limited to one side
T2 Tumor more than 5 cm in greatest dimension; limited to one side
T3 Tumor invades or encroaches on the ventricular system
T4 Tumor crosses the midline of the brain, invades the opposite hemisphere, or invades
infratentorially
Infratentorial tumor
T1 Tumor 3 cm or less in greatest dimension; limited to one side
T2 Tumor more than 3 cm in greatest dimension; limited to one side
T3 Tumor invades or encroaches on the ventricular system
T4 Tumor crosses the midline of the brain, invades the opposite hemisphere, or invades
supratentorially
N Nodal involvement
Not defined for this site
M Distant metastases
MX Presence of distant metastases cannot be assessed
M0 No distant metastases
M1 Distant metastases
From Beahrs OH, Henson DE, Hutter RVP, et al., eds. Manual for staging of cancer, 4th ed.
Philadelphia: JB Lippincott Co, 1992:247–252, with permission.
Pathology
• Primary intracranial tumors arise from the brain, cranial nerves, meninges, pituitary,
and vessels, and derive from ectoderm (brain) and mesoderm (vessels, meninges, blood components).
• The 1979 World Health Organization (WHO) classification of primary CNS tumors lists about 100 distinct pathologic subtypes of CNS malignancies in 12 broad categories (Table 15-3) (3).
• Histopathologic grade of malignancy is important because benign lesions have a
better prognosis and may be cured by surgery alone or radiation therapy below brain tolerance-dose levels.
Table 15-3: Histologic classification of tumors of the central nervous system
Neuroepithelial tumors Tumors of cranial/spinal nerves
Astrocytic tumors Schwannoma (neurilemoma)
Astrocytoma Neurofibroma
Anaplastic astrocytoma Tumors of the meninges
Glioblastoma Meningioma
Oligodendroglial tumors Atypical meningioma
Oligodendroglioma Anaplastic meningioma
Anaplastic oligodendroglioma Mesenchymal tumors, benign
Ependymal tumors Mesenchymal tumors, malignant
Ependymoma Hemangiopericytoma
Anaplastic ependymoma Chondrosarcoma
Mixed gliomas Malignant fibrous histiocytoma
Oligoastrocytoma Rhabdomyosarcoma
Anaplastic oligoastrocytoma Uncertain histogenesis
Choroid plexus tumors
Neurologic tumors Hemopoietic neoplasms
Ganglioglioma Malignant lymphomas
Anaplastic ganglioglioma Plasmacytoma
Neurocytoma Cysts/tumorlike lesions
Pineal parenchymal tumors Rathke cleft cyst
Pineocytoma Epidermoid cyst
Pineoblastoma Dermoid cyst
Embryonal tumors Sellar tumors
Medulloepithelioma Pituitary adenoma
Ependymoblastoma Craniopharyngioma
Primitive neuroectodermal tumors
From Wara WM, Bauman GJ, Sneed PK, et al. Brain, brainstem, and cerebellum. In: Perez CA, Brady LW, eds. Principles and practice of radiation oncology, 3rd ed. Philadelphia:
Lippincott–Raven, 1998:777–828, with permission.
Prognostic Factors
• Age, tumor type, tumor grade, seizure symptoms, duration of symptoms, performance
status, extent of surgery performed, and irradiation dose are important prognostic factors.
• The strongest prognostic factors for malignant astrocytomas, before irradiation has
been given, are (in order) age, tumor type, performance status, and extent of surgery
General Management
• During treatment, frequent attention must be paid to acute side effects that may
influence the patient's quality of life.
• Medications, performance and neurologic status, blood values, and the patient's
social situation must be monitored frequently to optimize his or her ability to accept and receive appropriate treatment.
• Glucocorticoids (usually dexamethasone) are used preoperatively, postoperatively,
and during the early phases of irradiation to decrease cerebral edema. They should be tapered to the lowest dose necessary to control symptoms; slow decreases in doses (i.e., 25% every 3 days) are necessary when steroid use is discontinued.
• Treatment for the primary tumor may alleviate seizures, but residual CNS injury may
continue to predispose to seizures. Phenytoin (Dilantin), carbamazepine (Tegretol), and phenobarbital are useful for generalized seizures; valproic acid and
carbamazepine are useful for partial seizures. Concomitant medications (such as glucorticoids) may alter anticonvulsant pharmacokinetics (particularly phenytoin); serum anticonvulsant levels should be checked regularly, particularly after medication changes.
• In most tumors, maximal safe surgical resection is associated with improved
prognosis; in some tumors, complete surgical resection may be curative.
• Some chemotherapy agents have demonstrated significant radiosensitizing effects in
the CNS (18).