Leptomeningeal Carcinomatosis

Involvement of the leptomeninges occurs in up to 5 percent of patients with breast cancer, usu ally in the setting of disseminated, progressive disease.25 As mentioned above, this complication is more commonly observed in patients with infiltrating lobular cancer. The majority of patients will present with neurologic signs referable to some combination of cerebrum, cranial nerves, and spinal cord, although the patient may complain only of a single symptom.26 The single-most common complaint is weakness of the legs, perhaps accompanied by pain or paresthesias. Cranial nerve involvement can produce diplopia, facial numbness or weakness, and hearing loss. Involvement of the cerebral cortex is heralded by headache, impaired memory, lethargy, and nausea.

Definitive diagnosis of leptomeningeal car-cinomatosis is difficult, as initial cytologic examination of the cerebrospinal fluid (CSF) is falsely negative in up to 46 percent of patients.27 Elevated CSF protein levels and monocytosis may be observed, and repeated sampling may yield positive cytology. Gadolinium-enhanced MRI of any areas of clinical involvement should be obtained, both to rule out parenchymal brain metastases or epidural cord compression and to detect enhancing, nodular meningeal enhancement—this may be seen along the convexity of the cerebrum, along the brain stem, or involving spinal nerve roots in up to 70 percent of patients.28

Treatment of leptomeningeal carcinomatosis is difficult, as it often arises in the midst of progressive systemic breast cancer and there has been no optimal approach established. Radiation therapy is usually administered to areas of bulky or symptomatic disease, although studies to establish this practice are lacking. Radiation therapy to the entire neuraxis is to be avoided as it can result in severe and prolonged myelosup-pression, thus preventing the subsequent administration of systemic chemotherapy.

As the entire neuraxis is potentially at risk for leptomeningeal spread, direct CSF installation of chemotherapy is also indicated. Because of improved distribution of drug throughout the CSF, intraventricular administration via an

Ommaya reservoir is preferred over lumbar puncture. Methotrexate 12 mg two or three times weekly has been used most often, with improvement reported in 60 to 80 percent of patients.26 29 The most common complication is transient aseptic meningitis, manifesting as headache, fever, and stiff neck. Particularly with simultaneous cranial radiotherapy, a necrotizing leukoencephalopathy with impaired mentation and focal defects may develop.29 Leakage of methotrexate outside of the CSF may result in mucositis or myelosuppression but may be counteracted by concurrent administration of oral or intravenous folinic acid. The median survival for patients who develop carcinomatosis meningitis is 3 to 6 months, although respon-ders may live in excess of 1 year.

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