Leptomeningeal carcinomatosis (Carcinomatous Meningitis)
Ovarian cancer does not commonly involve the nervous system. Brain metastasis is a rare complication of ovarian cancer with only 67 well documented cases in the literature until 1994. A multi-institutional study of 4027 ovarian cancer patients over 30 years identified only 32 cases while an autopsy study of ovarian cancer reported an incidence of 0.9%. Leptomeningeal metastasis (Carcinomatous Meningitis or Leptomeningeal Carcinomatous) is even a rarer complication of ovarian cancer with only 14 cases reported by 1994 (NCI).
The most common cancers to involve the leptomeninges are breast cancer, lung cancer and melanomas, and now, because of dose-intense combination chemotherapies, even ovarian cancer is more common.
Unfortunately, cancer cells are too small to find on any scans unless they have grown into a lump. There can still be cancer cells in the body even though scans may have indicated that all the cancer had gone. Leptomeningeal metastasis (Lepteomeningeal Carcinomatous or Carcinomatous Meningitis) is a condition caused by cancer cells getting into the thin sheets of body tissue that surround and protect the brain and spine. These sheets are called the meninges. Meningitis means inflammation of the meninges. Carcinomatous just means acting like a cancer. Most people are familiar with the type of meningitis caused by an infection, but with carcinomatous meningitis, it is the cancer cells in the meninges that cause the inflammation, not an outside infection.
Cancer cells do not always develop into an active secondary tumor when they have spread to a new site. Sometimes they stay inactive for many years. Even after a cancer appears to have been successfully treated, some cancer cells may still be elsewhere in the body. No one knows why some cancer cells stay inactive or what triggers them to form a secondary cancer.
Tumor cells reach the meninges by hematogenous (blood) spread or by direct extension from pre-existing lesions and are then disseminated throughout the neuroaxis by the flow of the cerebrospinal fluid. Patients present with signs and symptoms from injury to nerves that traverse the subarachnoid space, direct tumor invasion into the brain or spinal cord, alterations in blood supply to the nervous system, obstruction of normal cerebrospinal fluid (CSF) flow pathways or general interference with brain function.
Secondary cancers from a primary cancer can develop in different parts of the body, including the brain or spine. Cancer cells do not always develop into an active secondary tumor when they have spread to a new site. Sometimes they stay inactive for many years. So, even after a cancer appears to have been successfully treated, some cancer cells may still be elsewhere in the body. No one knows why some cancer cells stay inactive or what triggers them to form a secondary cancer.
Symptoms from neoplastic meningitis include pain, headaches, mental status decline, loss of sensation in the face or elsewhere on the body, or difficulties with vision, hearing, or swallowing, among others. Diagnosis is most commonly made by lumbar puncture, although the CSF cytology is persistently negative in about 10% of patients with leptomeningeal carcinomatosis. Radiology studies may reveal subarachnoid masses, diffuse contrast enhancement of the meninges or hydrocephalus without a mass lesion.
Doctors estimate that about 5 out of every 100 patients who have cancer develop carcinomatous meningitis. It is most common in breast cancer, but it can occur with any type of cancer. The cancer cells in the meninges can cause a range of symptoms, including confusion, headaches and weakness.
The condition is very difficult to treat. The main aim is to help control symptoms and not cure the disease. Chemotherapy injected into the spinal fluid (via Ommya Reservoir in the brain) or radiotherapy to the brain are both treatments for Carcinomatous meningitis. Some patients respond to these treatments, but the prognosis is generally poor. There are no set guidelines for treating this condition as oncologists don't really know which treatments work best.
Without treatment, the median survival of patients is 4 - 6 weeks and death occurs from progressive neurologic dysfunction. Radiation therapy to symptomatic sites and disease visible on neuroimaging studies and intrathecal chemotherapy increases the median survival to 3 - 6 months. Major favorable prognostic factors include excellent performance status, absence of serious fixed neurologic deficits, normal CSF flow scans and absent or responsive systemic tumor.
Oncologists have been looking at using different combinations of chemotherapy drugs to treat Leptomenigeal Carcinomatous secondary to the primary cancer (Chemosensitivity Testing may help in this process). They found that giving both chemotherapy injected into the bloodstream and chemotherapy given directly into the spinal fluid may improve the outlook for some people. However, current available therapies are toxic though, and provide limited benefits.
Approximately 50% of lung and breast cancer patients who survive more than one year with Leptomeningeal metastasis treated with repeated injections of intrathecal methotrexate develop leukoencephalopathy which includes confusion, dementia, somnolence or focal neurologic signs. This usually occurs when intrathecal methotrexate is combined with irradiation and this combination should be avoided if possible. The leukoencephalopathy may improve if intrathecal methotrexate is discontinued, although it may also progress to coma and death. Leucovorin is a faster acting and more potent form of folic acid. It is used as a rescue after dose-intense methotrexate therapy to lessen and counteract the effects of methotrexate toxicity and other folic acid antagonists.
A medical oncologist involved with Chemosensitivity Testing has stated that their lab has only received maybe four Lepomeningeal Carcinomatous specimens over the years. Of those, only one specimen had sufficient tumor cells for testing. The problem is that it requires a specimen of cerebrospinal fluid, and it's not safe (with LC) to take more than a few ml of spinal fluid, and there are typically not enough cells to test more than one drug, if that. If there would be another site of the disease (lymph node, pleural fluid, etc.), then that could be biopsied. The biology of the disease, in all probability, would be similar to that of the lymph node, pleural fluid, etc. tumor.
If an assay test could not be performed and the disease had to be treated empirically, one protocol could be giving intrathecal thiotepa plus systemic gemcitabine (the gemcitabine given prior to the thiotepa). Thiotepa may be safely given intrathecally. Gemcitabine can probably be given intrathecally (it is somewhat similar to cytarabine), but it is thought that no one has ever done a clinical trial to prove that this is feasible and safe. In principal, the best shot would be to give intrathecal gemcitabine + intrathecal thiotepa.
Another alternative to Methotrexate is Cytarabine (cytosine arabinoside) or Ara-C. It is an anti-metabolite (like Methotrexate) which stops cells making and repairing DNA. Cancer cells need to make and repair DNA in order to grow and multiply. Ara-C is a clear liquid that can be dripped into a vein (intravenous infusion), into the spinal fluid (intrathecally) or by an injection just under the skin (subcutaneously).
Last edited by gdpawel on Mon Aug 01, 2005 12:22 pm, edited 1 time in total.