Leptomeningeal Carcinomatosis Follow-up

Updated: Jun 24, 2016
  • Author: Michael J Schneck, MD, MBA; Chief Editor: Stephen A Berman, MD, PhD, MBA  more...
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Follow-up

Further Inpatient Care

Once intrathecal chemotherapy has been initiated for leptomeningeal carcinomatosis (LC), check CSF cytology every 4 weeks.

If the cytologic result is negative, continue chemotherapy at the same rate of twice a week for 2 more weeks, then decrease the frequency to twice a week for 1 week a month, followed by further CSF monitoring every two months.

If the CSF cytologic results remain positive, continue the chemotherapy at the same rate, change the chemotherapeutic agent, or reclassify patient as poor risk and administer palliative treatment.

Supportive care should include anticonvulsants for seizure control, adequate analgesia with opioids, and antidepressants and anxiolytics as needed. Corticosteroids may help vasogenic edema associated with metastases (although they have limited effect on neurologic symptoms associated with LC), and may be combined with antiemetics for treatment of chemical meningitis. Psychostimulants can help with inattention and somnolence secondary to whole-brain radiation.

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Complications

Hydrocephalus

The most common complication is hydrocephalus, which results when tumor occludes the CSF outflow foramina of the fourth ventricle and the inflammatory response decreases CSF reabsorption.

A rapidly developing hydrocephalus causes increased ICP, occasionally leading to herniation of the tentorium and cerebellum, while a slowly developing hydrocephalus can cause dilatation of the ventricles without an increase in ICP, confusing the diagnostician if this is the presenting sign.

Even in the absence of hydrocephalus, flow abnormalities are present in 70% of patients with LC, adversely affecting the distribution of intrathecal chemotherapy.

Other complications

LC may cause seizures or other neurologic dysfunction by invading the parenchyma of the brain or Virchow-Robin spaces or cause areas of ischemia or infarction by interfering with blood supply.

Competition for glucose between malignant cells and neurons can lead to hypofunction in affected areas. For example, in hypothalamic leukemia, weight gain in patients in leukemic remission can signify relapse because hypothalamic hypoglycorrhachia is induced by local competition for glucose by metastatic tumor cells.

LC also causes partial disruption of the blood-brain barrier once the tumor size has increased enough to stimulate growth of its own vasculature.

Treatment-related complications can result from catheter placement, chemotherapy, or radiation.

Catheter placement causes perioperative complications (1% of patients), and after placement, the catheter tip can migrate into the brain tissue, obstruct the shunt, or, more commonly, cause infection (usually Staphylococcus epidermidis, in 5% of patients).

MTX administration can cause acute arachnoiditis (nausea, vomiting, mental status changes), seizures, mucositis, or myelosuppression (mitigated with folinic acid coadministration, 10 mg q6h for 24 h).

Meningeal irritation, characterized by headache, fever, stiff neck (sometimes), confusion, and disorientation, often develops several hours following intrathecal MTX administration but is self-limiting and resolves within 24-72 hours. This can be treated on an outpatient basis with antipyretics, antiemetics, and corticosteroids.

Transverse myelitis is a rare idiosyncratic reaction to MTX that begins 30 min to 48 h after intrathecal treatment and presents with paraplegia, leg pains, and development of a sensory level and bladder dysfunction; it should be distinguished from traumatic spinal subdural hematoma. Again, no specific treatment is available but some improvement can occur over days to months.

Leukoencephalopathy is the most serious complication; it appears a year after treatment and is more likely in those who have also undergone cranial radiation. It presents as a progressive encephalopathy, often with ataxia, dysarthria, and focal findings.

Cytarabine, like MTX, also may cause meningism, headache, and fever.

Thiotepa causes less neurologic toxicity than MTX; the most common effect is transient limb paresthesias. Unlike MTX, there is no way of mitigating the resultant myelosuppression.

Radiation can cause myelosuppression and increase the neurotoxicity of intrathecal chemotherapy. Necrotizing leukoencephalopathy is most common after a combination of MTX and cranial irradiation. Initial findings are changes in the white matter on neuroimaging after 6 months of therapy; progressive dementia and other neurologic complications develop later. Other complications are delayed cerebral radiation necrosis, acute transverse myelopathy, chronic progressive myelopathy, and acute brachial plexus lesions.

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Prognosis

The prognosis is generally poor because LC usually signifies the presence of metastases elsewhere, and the course of the systemic cancer is the major determinant of the patient's survival. [11] Untreated, median survival is 4-6 weeks; treated, median survival is 2-3 months [3] . However, small case series have suggested prolonged survival with newer chemotherapeutic regimens for diseases such as breast and lung cancers. The most notable exception is leukemic or lymphomatous meningitis, which is sensitive to both MTX and Ara-C and often can be eradicated completely from the CNS. Poor prognostic indicators include the following:

  • Poor (Karnofsky) performance status
  • Multiple, serious neurologic deficits
  • Extensive systemic disease with few treatment options
  • Coexistent carcinomatous encephalopathy
  • CSF flow abnormalities on radionuclide ventriculography
  • Bulky CNS disease

Among patients with LC from solid tumors, the best response to chemotherapy and radiation occurs in those with LC from breast cancer, with 60% improving or stabilizing and a median survival of 7 months; 15% survive for a year, a survival rate rare in patients with LC with a primary tumor other than breast.

Only 40% of LCs from small-cell lung carcinoma improve or stabilize, and patients with this disease have a median survival of only 4 months.

Melanoma-derived LC carries a 3.6-month median survival, and only 20% of these patients stabilize or improve with treatment.

Nonresponders to chemotherapy seldom survive longer than a month. This prognosis has not improved measurably in the last 20 years despite an increase in incidence and diagnosis.

The most useful prognostic indicator is the Karnofsky scale (KS) score. Patients with a KS score of 70 or higher survive for a mean of 313 days, whereas those with a score of 60 or lower survive for a mean of only 36 days.

Tumor response 2 weeks after the initiation of treatment is a good portent.

Progressive multilevel involvement or rapid progression in 1 or more CNS lesions is ominous.

In a single-center study of 135 patients older than 50 years assessed between 1989 and 2005, with Karnofsky performance status ≤70%, and an interval between diagnosis of primary tumor and leptomeningeal metastases (LM) ≤12 months, presence of either lung cancer or malignant melanoma were negative prognostic factors. Only treatment with systemic chemotherapy was associated with longer survival consistent with the principle that better outcomes are reached with systemic disease. [34]

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Patient Education

For excellent patient education resources, visit eMedicineHealth's Cancer Center. Also, see eMedicineHealth's patient education article Brain Cancer.

Information on ongoing clinical trials is available at https://clinicaltrials.gov/ct2/results?term=leptomeningeal&Search=Search. Patients should discuss their interest in such trials with their oncologist and other trusted medical advisors.

Medscape Palliative Care Guidelines: http://emedicine.medscape.com/article/2500043-overview

WebMD Palliative Care Information: http://www.webmd.com/palliative-care/palliative-care-topic-overview

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