Brain Lymphoma

[ericzhu]

My father is in China now, 56 years old. Start from 1996, he was diagnosed as primary throbocythemia, then he began to take Hydroxycarbamide Tablets periodically. Since May.2006, he began to feel sick, dizzy, hypomnesia, till fall down on the floor. Through biopsy inspection, it’s brain lymphoma. He received radiotherapy and chemotherapy, the dispersed tumor disappeared. But 3 months later, my father began to show a mental problem, he kept asking same question again and again, it seems his memory is still in 30 years ago, sometimes make big noise and it became more and more often. In Sep.2008, the tumor recurred again... it seems it's more dangerous than before.

I want to consult is there any better therapy to extend my father’s life. My father is still young, I feel helpless but I don't want to give up.
Could anyone give me a help? If anyone has a good suggestion, pls send me a mail: ericzwh@hotmail.com, thanks!

[gpawelski]

I gather when you say Brain Lymphoma, you are talking about Leptomeningeal Carcinomatous (LC) or Carcinomatous Meningitis (CM) from Lymphoma. There are no lymph nodes in the brain. However, a lymphoma can metastasize to the brain.

Although I have this listed under Breast Cancer on the website, it still applies to Lymphoma metastasis to the brain.

What is Carcinomatous Meningitis (Leptomeningeal Carcinomatous)?

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.

Carcinomatous Meningitis (Lepteomeningeal Carcinomatous or Leptomeningeal metastasis) 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.

Diagnosis is most commonly made by lumbar puncture, to look for malignant cells or elevated protein levels in the spinal fluid, although the CSF cytology is persistently negative in about 10% of patients with leptomeningeal carcinomatosis. A MRI of the brain and spine to look for enhancement of meningeal tissue. 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, also head pain, cranial nerve involvement, hearing problems and back pain.

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.

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.

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).

There have been some clinical trials using Temodar (temozolomide) instead of Methotrexate, Ara-C, or combination gemcitabine (Gemzar) plus Thiotepa in treating patients with CM from a solid tumor.

[ericzhu]

Hi George, Thanks again for your feedback. Checked with dictionary, my father's brain lymphoma is called Primary Central Nervous System Lymphoma. He is receiving chemotherapy in Shanghai China, hope he can get recovery this time.

[gpawelski]

Lymphomatous Meningitis in Primary Central Nervous System Lymphoma. Looks like treatment is the same.

According to research published in the January 29, 2008, issue of the medical journal Neurology, patients who receive high-dose Methotrexate alone or in combination with other chemotherapy durgs appear to live longer than patients receiving other treatments. Further studies are needed to identify the optimal Methotrexate dose and combination therapy that will produce the most effective results with minimum side effects. It appears some people may achieve a long remission through the Methotrexate alone, according to the study's author, Dr. Tracy Batchelor.

My wife received intrathecal Methotrexate along with systemic radiation to the spine. When both therapies are performed at the same time it doubles the therapeutic dosages of each therapy, increasing the neuro-toxic effects on the brain. Although Leptomeningeal Carcinomatous has a very poor prognosis, the cancer cells were eradicated completely from her central nervous system.

Again, there have been some clinical trials (completed) using Temodar (temozolomide) instead of Methotrexate, in treating patients with Leptomeningeal Metastases from a solid tumor or Lymphoma.

http://clinicaltrials.gov/ct/show/NCT00005812?order=11

http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=67814&version=patient

You should take a look at Musella's Virtual Trials and Noteworthy Treatment for Brain Tumors website: http://www.virtualtrials.com/