Neoplasias de SNC Flashcards
Como fazer a avaliação radiológica de tumores de SNC?
Cranial MRI is the preferred diagnostic test for any patient suspected of having a brain tumor, and should be performed with gadolinium contrast administration. CT scan should be reserved for those patients unable to undergo MRI (e.g., pacemaker). Malignant brain tumors—whether primary or metastatic—typically enhance with gadolinium 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 with gadolinium and are best appreciated on fluid-attenuated inversion recovery (FLAIR) MR images. Meningiomas have a characteristic appearance on MRI as they are dural-based with a dural tail and compress but do not invade the brain. Dural metastases or a dural lymphoma can have a similar appearance. Imaging is characteristic for many primary and metastatic tumors, but occasionally there is diagnostic uncertainty based on imaging alone. In such patients a brain biopsy may be helpful in determining a definitive diagnosis. However, when a tumor is strongly suspected, the biopsy can be obtained as an intraoperative frozen section before a definitive resection is performed. Neuroimaging is the only test necessary to diagnose a brain tumor.
Quais os pilares do tratamento da neoplasia cerebral?
Therapy of any intracranial malignancy requires both symptomatic and definitive treatments.
(1) Definitive treatment is based upon the specific tumor type and includes surgery, radiotherapy (RT), and chemotherapy.
(2) Glucocorticoids are highly effective at reducing perilesional edema and improving neurologic function, often within hours of administration. Dexamethasone has been the glucocorticoid of choice because of its relatively low mineralocorticoid activity. Initial doses are typically 12 mg to 16 mg a day in divided doses given orally or IV (both are equivalent). While glucocorticoids rapidly ameliorate symptoms and signs, their longterm use causes substantial toxicity including insomnia, weight gain, diabetes mellitus, steroid myopathy, and personality changes. Consequently, a taper is indicated as definitive treatment is administered and the patient improves.
(2) Patients with brain tumors who present with seizures, require anticonvulsant drug therapy. There is no role for prophylactic anticonvulsant drugs in patients who have not had a seizure, thus their use should be restricted to those who have had a convincing ictal event. The agents of choice are those drugs that do not induce the hepatic microsomal enzyme system. These include levetiracetam, topiramate, lamotrigine, valproic acid, or lacosamide (Chap. 26). Other drugs such as phenytoin and carbamazepine are used less frequently because they are potent enzyme inducers that can interfere with both glucocorticoid metabolism and the metabolism of chemotherapeutic agents needed to treat the underlying systemic malignancy or the primary brain tumor.
(3) Venous thromboembolic disease occurs in 20–30% of patients with high-grade gliomas and brain metastases. Therefore, anticoagulants should be used prophylactically during hospitalization and in patients who are nonambulatory. Those who have had either a deep vein thrombosis or pulmonary embolus can receive therapeutic doses of anticoagulation safely and without increasing the risk for hemorrhage into the tumor. Inferior vena cava filters are reserved for patients with absolute contraindications to anticoagulation such as recent craniotomy.
Qual o tratamento do linfoma primário do SNC?
Unlike other primary brain tumors, PCNSL is relatively sensitive to glucocorticoids, chemotherapy, and radiotherapy.
(1) High-dose methotrexate, a folate antagonist that interrupts DNA synthesis, produces response rates ranging from 35 to 80% and median survival up to 50 months
(2) Combination of methotrexate with other chemotherapeutic agents such as cytarabine, as well as whole-brain radiotherapy, increases the response rate to 70–100%. However, radiotherapy is associated with delayed neurotoxicity, especially in patients over the age of 60 years.
(3) There is emerging evidence that the anti-CD20 monoclonal antibody rituximab may have activity in PCNSL, although there remain concerns about its ability to pass through the blood-brain barrier as it becomes reconstituted with therapy
(4) At least 50% of patients will eventually develop recurrent disease. Treatment options include radiotherapy for patients who have not had prior irradiation, re-treatment with methotrexate, as well as other agents such as temozolomide, rituximab, procarbazine, topotecan, and pemetrexed. High-dose chemotherapy with autologous stem cell rescue may have a role in selected patients with relapsed disease.
(5) In organ transplant recipients, reduction of immunosuppression may improve outcome. In HIV, these patients may be treated with whole-brain radiotherapy, high-dose methotrexate, and initiation of highly active antiretroviral therapy.
Como fazer o diagnóstico de linfoma primario de SNC?
PCNSL in immunocompromised patients often produces multiple-ring enhancing lesions that can be difficult to differentiate from metastases and infections such as toxoplasmosis. The diagnosis is usually established by examination of the cerebrospinal fluid for cytology and EBV DNA, toxoplasmosis serologic testing, brain PET imaging for hypermetabolism of the lesions consistent with tumor instead of infection, and, if necessary, brain biopsy.
Quais as três opções terapêuticas do linfoma primario de SNC?
(1) RADIATION THERAPY The standard treatment for brain metastases has been whole-brain radiotherapy (WBRT) usually administered to a total dose of 3000 cGy in 10 fractions. This affords rapid palliation, and approximately 80% of patients improve with glucocorticoids and radiation therapy. However, it is not curative. Median survival is only 4–6 months. More recently, stereotactic radiosurgery (SRS) delivered through a variety of techniques including the gamma knife, linear accelerator, proton beam, and CyberKnife all can deliver highly focused doses of RT, usually in a single fraction. SRS can effectively sterilize the visible lesions and afford local disease control in 80–90% of patients. In addition, there are some patients who have clearly been cured of their brain metastases using SRS, whereas this is distinctly rare with WBRT. However, SRS can be used only for lesions 3 cm or less in diameter and should be confined to patients with only 1–3 metastases. The addition of WBRT to SRS improves disease control in the nervous system but does not prolong survival.
(2) SURGERY Randomized controlled trials have demonstrated that surgical extirpation of a single brain metastasis followed by WBRT is superior to WBRT alone. Removal of two lesions or a single symptomatic mass, particularly if compressing the ventricular system, can also be useful. This is particularly useful in patients who have highly radioresistant lesions such as renal carcinoma. Surgical resection can afford rapid symptomatic improvement and prolonged survival. RT administered after complete resection of a brain metastasis improves disease control but does not prolong survival.
(3) CHEMOTHERAPY Chemotherapy is rarely useful for brain metastases. Metastases from certain tumor types that are highly chemosensitive, such as germ cell tumors or small cell lung cancer, may respond to chemotherapeutic regimens chosen according to the underlying malignancy. Increasingly, there are data demonstrating responsiveness of brain metastases to chemotherapy including small molecule–targeted therapy when the lesion possesses the target. This has been best illustrated in patients with lung cancer harboring EGFR mutations that sensitize them to EGFR inhibitors. Antiangiogenic agents such as bevacizumab may also prove efficacious in the treatment of CNS metastases
Qual o tratamento das metástases leptomeningeas?
The treatment of leptomeningeal metastasis is palliative as there is no curative therapy. RT to the symptomatically involved areas, such as skull base for cranial neuropathy, can relieve pain and sometimes improve function. Whole neuraxis RT has extensive toxicity with myelosuppression and gastrointestinal irritation as well as limited effectiveness. Systemic chemotherapy with agents that can penetrate the blood-CSF barrier may be helpful. Alternatively, intrathecal chemotherapy can be effective, particularly in hematologic malignancies. This is optimally delivered through an intraventricular cannula (Ommaya reservoir) rather than by lumbar puncture. Few drugs can be delivered safely into the subarachnoid space and they have a limited spectrum of antitumor activity, perhaps accounting for the relatively poor response to this approach. In addition, impaired CSF flow dynamics can compromise intrathecal drug delivery. Surgery has a limited role in the treatment of leptomeningeal metastasis, but placement of a ventriculoperitoneal shunt can relieve raised intracranial pressure. However, it compromises delivery of chemotherapy into the CSF
Qual o tratamento das metástases epidurais?
Epidural metastasis requires immediate treatment. A randomized controlled trial demonstrated the superiority of surgical resection followed by RT compared to RT alone. However, patients must be able to tolerate surgery, and the surgical procedure of choice is a complete removal of the mass, which is typically anterior to the spinal canal, necessitating an extensive approach and resection. Otherwise, RT is the mainstay of treatment and can be used for patients with radiosensitive tumors, such as lymphoma, or for those unable to undergo surgery. Chemotherapy is rarely used for epidural metastasis unless the patient has minimal to no neurologic deficit and a highly chemosensitive tumor such as lymphoma or germinoma. Patients generally fare well if treated before there is severe neurologic deficit. Recovery after paraparesis is better after surgery than with RT alone, but survival is often short due to widespread metastatic tumor.
