Neurologic complications of cancer and cancer therapy.

When neurologic complications occur as a result of systemic cancer and cancer treatment, they can be more disabling for patients than their primary cancer and significantly impair functioning in varied domains. However, recognizing neurologic signs and symptoms as complications of cancer and its treatment can pose a challenge for healthcare providers. Oncology nurses must develop a high index of suspicion for neurologic complications when examining or interviewing patients who present with neurologic symptoms or deficits and have a known systemic cancer. The purpose of this article is to help oncology nurses identify the common presentations of those complications and understand the ways in which they occur, with the hope that early identification will facilitate appropriate medical intervention and slow the progression of neurologic deficits and systemic decline.

Neoplastic meningitis.

Neoplastic meningitis occurs in approximately 5%-10% of all patients with cancer, and aggressive supportive measures are a critical component of comprehensive care. A literature review of the current diagnostic methods, randomized controlled trials, and available treatments was undertaken; and a comprehensive discussion of best-practice supportive care measures is provided. Although the prognosis for those diagnosed with neoplastic meningitis is poor, treatment and supportive care may allow stabilization of neurologic symptoms and afford protection from further neurologic deterioration, allowing patients to maximize their function and independence and adjust their expectations of treatment from cure to palliation.

Route of intracerebrospinal fluid chemotherapy administration and efficacy of therapy in neoplastic meningitis.

BACKGROUND: A study was undertaken to determine whether route (intraventricular vs intralumbar) of intracerebrospinal fluid (intra-CSF) drug administration influences progression-free survival in the treatment of patients with neoplastic meningitis, which occurs in 1% to 5% of patients with known cancer. Currently available treatment options result in modest responses, which is in part a reflection of obstacles to drug delivery into the leptomeningeal space. METHODS: One hundred patients with clinically and cytologically or radiographically documented neoplastic meningitis because of solid cancers received intra-CSF liposomal cytarabine or methotrexate as specified in a randomized phase 4 trial. The 2 treatment arms were well balanced for demographic and tumor-related characteristics of known prognostic importance, including age, performance status, tumor type, extent of systemic and other central nervous system (CNS) disease, prior CNS therapy, and concurrent systemic chemotherapy. RESULTS: One hundred patients were randomized and treated (52 with sustained-release cytarabine, and 48 with methotrexate). Progression-free survival (the primary study endpoint) was identical between the sustained-release cytarabine and methotrexate treatment arms for all 100 patients (35 vs 37.5 days, P = .79). When progression-free survival was examined as a function of route of chemotherapy administration (lumbar vs ventricular), there was no difference for patients treated with sustained-release cytarabine (29 vs 43 days, P = .35). For patients treated with methotrexate, however, there was a statistically significant difference favoring patients receiving intraventricular therapy (19 vs 43 days, P = .048). CONCLUSIONS: Site of intra-CSF chemotherapy drug administration is clinically relevant with short half-life drugs such as methotrexate.

Gender disparity in the rate of partner abandonment in patients with serious medical illness.

BACKGROUND: Life-threatening illness creates severe stress that may result in marital discord, separation, or divorce and may adversely impact treatment, quality of life, and survival. The few studies that are available to date have suggested that the risk of divorce is not higher in cancer patients, but to the authors' knowledge, no data exist to date that have examined the effect of gender on this rate. METHODS: A total of 515 patients were prospectively identified as having either a malignant primary brain tumor (N = 214), a solid tumor with no nervous system involvement (N = 193), or multiple sclerosis (N = 108) who were married at the time of diagnosis. Basic demographic information and data regarding marital status were compiled. Patients were followed prospectively from enrollment until death or study termination. RESULTS: Women composed 53% of the patient population. Divorce or separation occurred at a rate similar to that reported in the literature (11.6%). There was, however, a greater than 6-fold increase in risk after diagnosis when the affected spouse was the woman (20.8% vs 2.9%; P < .001). Female gender was found to be the strongest predictor of separation or divorce in each cohort. Marriage duration at the time of illness was also correlated with separation among brain tumor patients (P = .0001). Patients with brain tumors who were divorced or separated were more likely to be hospitalized, and less likely to participate in a clinical trial, receive multiple treatment regimens, complete cranial irradiation, or die at home (P < .0001). CONCLUSIONS: Female gender was found to be a strong predictor of partner abandonment in patients with serious medical illness. When divorce or separation occurred, quality of care and quality of life were adversely affected.

Lymphomatous meningitis: early diagnosis and treatment.

The incidence of central nervous system (CNS) metastases has increased steadily since 1999, likely because of the use of drugs with poor access to the CNS as well as the successful treatment of extraneural cancers, resulting in longer survival.Lymphomatous meningitis is a profoundly morbid and often fatal CNS metastasis that develops in at least 4%-8% of patients with non-Hodgkin lymphoma.Risk factors for lymphomatous meningitis include uncontrolled systemic and extranodal disease, testicular and parasinus tumors, and being younger than age 60. A high index of suspicion for the condition may result in earlier detection and improved outcome.Lymphomatous meningitis diagnostic methods include a thorough neurologic examination, magnetic resonance imaging (MRI), and multiple samplings of cerebrospinal fluid (CSF). Treatment regimens typically include radiation to areas of bulky disease or intrathecal chemotherapy.Available chemotherapeutic agents include methotrexate, cytarabine, and liposomal cytarabine.In addition to follow-up CSF and MRI monitoring, questioning patients and caregivers can provide insight into treatment response in terms of quality of life.Special care to avoid a nihilistic outlook in patients and clinicians is essential in treating patients with lymphomatous meningitis.

Recurrent lymphomatous meningitis treated with intra-CSF rituximab and liposomal ara-C.

BACKGROUND: The most frequent central nervous system complication of systemic non-Hodgkin's lymphoma (NHL) is lymphomatous meningitis (LM). OBJECTIVE: A clinical series to test the feasibility of combining intra-CSF liposomal ara-C and rituximab for the treatment of recurrent LM. DESIGN: Clinical series of 14 patients with CSF positive lymphomatous meningitis. SETTING: Tertiary-care university medical center. RESULTS: Fourteen patients with recurrent, cytologically positive lymphomatous meningitis were treated. All 14 received liposomal ara-C and rituximab utilizing an Ommaya reservoir. Six patients also received involved-field radiotherapy (brain only two patients; brain and spine two patients; spine only two patients). Best response to treatment included 10 partial responses and four with progressive disease. Estimated median duration of response was 4.0 months (range 1-6 months). Survival ranged from 1.5 to 7 months with an estimated median of 5 months, four patients remain alive and continue to be followed. Cause of death was progressive neurological disease in 7, systemic disease in 1, and combined systemic and neurological disease in 2 patients. CONCLUSIONS: The combination of intra-CSF liposomal ara-C and rituximab administered in this schedule appears to have no additive toxicity and has modest palliative activity in patients with recurrent LM.

Managing reduced methotrexate clearance in a patient with a heterozygous methylenetetrahydrofolate reductase gene polymorphism.

High dose methotrexate has become one of the treatments of choice for patients with primary CNS lymphomas due to its ability to penetrate the blood-brain barrier. A potentially serious complication of this therapy is methotrexate-related nephrotoxicity. We report the case of a patient with a common genetic polymorphism that may have predisposed this patient experience clinically significant toxicity from systemic folate depletion. After the first cycle of chemotherapy that included high dose methotrexate, the patient's serum creatinine rose and the patient's methotrexate level remained above the toxic range for six days. On cycle two, the patient was treated with a 25% dose reduction in methotrexate and more aggressive hydration and alkalization. With this alteration in the regimen, the patient was able to receive six more cycles and had a complete radiographic tumor response in the brain and a disappearance of tumor cells in the CSF without any further renal complications. This case report illustrates the feasibility of administering high dose methotrexate with modifications as a treatment of choice in individuals with methylenetetrahydrofolate reductase gene mutations.

Early necrosis following concurrent Temodar and radiotherapy in patients with glioblastoma.

Concurrent temozolomide (TMZ) and radiotherapy is the new standard of care for patients with newly diagnosed glioblastoma. In 51 consecutive patients treated according to this regimen, 7 patients (14%) manifested surgically confirmed early necrosis without evidence of recurrent tumor. This observation suggests that daily TMZ may represent a potent radiosensitizing regimen.