| Author |
|
gdpawel
Senior User
Joined: 15 Jan 2005
Posts: 123
Location: Pennsylvania
|
 Posted: Sat Jan 22, 2005 2:36 am Post subject: Carcinomatous Meningitis |
 |
|
Leptomeningeal Carcinomatous (Carcinomatous Meningitis)
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.
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 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 1:26 pm; edited 1 time in total |
|
| Back to top |
|
|
|
gdpawel
Senior User
Joined: 15 Jan 2005
Posts: 123
Location: Pennsylvania
|
| Posted: Tue Jun 07, 2005 8:30 pm Post subject: CARCINOMATOUS MENINGITIS: TAXANE INDUCED? |
|
|
CARCINOMATOUS MENINGITIS: TAXANE INDUCED?
Isolated Leptomeningeal Carcinomatosis (Carcinomatous Meningitis) after Taxane-Induced Major Remission in Patients with Advanced Breast Cancer
Christos Kosmasa, Nikolaos A. Malamosa, Nikolas B. Tsavarisc, Melina Stamatakib, Achilleas Gregorioua, Sofia Rokanaa, Maria Vartholomeoua, Minas J. Antonopoulosa
aDepartment of Medicine, Medical Oncology Unit and bDepartment of Cytopathology, Helena-Venizelou Hospital and cDepartment of Pathophysiology, Medical Oncology Unit, Laikon General Hospital, Athens University School of Medicine, Athens, Greece
Abstract
Objectives: To identify the incidence of leptomeningeal carcinomatosis (LMC), as the first site of systemic progression, in breast cancer patients after having obtained a major response (CR or near CR) to first-line taxane-based chemotherapy and compare these findings in retrospect with a matched-pair group of historical control patients from our database treated with nontaxane regimens.
Patients and Methods: Patients with histologically proven breast cancer having either metastatic disease or high-risk locoregional disease that were entered into treatment protocols with first-line taxane (paclitaxel or docetaxel) plus anthracyclines or mitoxantrone combinations and developed LMC as the first evidence of progression after major response (CR or >80% PR) were analyzed in the present study (n = 155), and compared, as regards the incidence of LMC, to a matched-pair retrospective group of 155 patients treated with nontaxane regimens in our unit.
Results: Seven patients with a median age of 54 years (range 40-70) developed LMC as their first evidence of progression after taxane-based regimens with a median interval of 6 months (range 2-18) from start of treatment to diagnosis of LMC. Five patients received intrathecal (i.t.) methotrexate treatment and whole brain radiotherapy (RT), while 1 patient received i.t. methotrexate and RT to the lumbar spine.
Two patients responded to treatment for LMC, while 2 achieved stable disease and 3 progressed. Two patients had elevated cerebrospinal fluid tumor markers (more than serum marker levels) that proved useful in monitoring response to treatment. Median survival after LMC was 3.6 months (range 1-17+) and correlated positively to the interval from the initiation of taxane-based therapy to LMC (r = 0.84, p = 0.019).
Seven out of 86 responders (8.13%) in the taxane group versus 1 out of 72 responders (1.4%) in the non-taxane-treated group developed LMC as the first sign of progression after a major response to first-line chemotherapy (p < 0.1).
Conclusions: LMC after a major response to front-line taxane-based regimens represents a grave disease manifestation and its incidence appears increased, but not significantly so, when compared retrospectively to non-taxane-treated patients.
Prospective evaluation of the incidence of LMC after taxane versus non-taxane-based treatment from large randomized multi-institutional trials is warranted and identification of potential prognostic factors might help to identify patients requiring appropriate prophylactic therapy.
American Journal Clinical Oncology 2002;63:6-15 |
|
| Back to top |
|
|
|
gdpawel
Senior User
Joined: 15 Jan 2005
Posts: 123
Location: Pennsylvania
|
| Posted: Mon Jul 11, 2005 2:51 am Post subject: Neoadjuvant Taxol Chemo May Cause Breast Tumor Cell Release |
|
|
As reported at the 27th Annual San Antonio Breast Cancer Symposium (abstract 6014), using a technique that quantifies circulating tumor cells, German investigators from Friedrich-Schiller University in Jena, have shown that neoadjuvant chemotherapy with paclitaxel (taxol) causes a massive release of cells into the circulation, while at the same time reducing the size of the tumor. The finding could help explain the fact that complete pathologic responses do not correlate well with improvements in survival.
In the study, according to Katharina Pachmann, M.D., professor of experimental oncology and hematology, breast cancer patients undergoing neoadjuvant chemotherapy gave blood samples in which epithelial antigen-positive cells were isolated. Such cells are detected in most breast cancer patients but are rarely found in normal subjects. The investigators measured the levels of cirulating tumor cells before and during primary chemotherapy with several different cytotoxic agents.
Paclitaxel (taxol) produces the greatest degree of tumor shrinkage but also the greatest release of circulating tumor cells. In three different paclitaxel-containing regimens, circulating cell numbers massively increased, whereas tumor size decreased. These cells remained in the circulation for at least five months after surgery.
The tumor shrinks, but more cells are found in the circulation. This corresponds with a high pathologic complete response during paclitaxel treatment, but in the end, this is not reflected in improved survival. These cells are alive in the circulation. The results indicate that monitoring of circulating tumor cells can contribute to understanding of tumor-blood interactions and may provide a valuable tool for therapy monitoring in solid tumors.
(Oncol News Int'l, Vol 14, #5, May '05)
What this recent study has shown, so far, that in three different paclitaxel (taxol) containing regimens, as the tumor collapses (a clinical response, not cure), it produces the greatest release of circulating tumor cells. The study has not looked at any other combination regimens.
With these cells being alive in the circulation, it may mean that a patient with invasive breast cancer without lymph node involvement (where systemic treatment "may" benefit), or a patient with invasive breast cancer that involves lymph nodes (where systemic treatment is "usually" recommended), would need additional (anti-estrogen) treatment, such as Tamoxifen (it may be given alone or in addition to chemotherapy, if given).
It has been shown that Tamoxifen treatment will reduce circulating tumor cells in some patients, but not all. It has been shown that Herceptin treatment will reduce circulating tumor cells in patients with HER2-negative tumors, but less pronounced in HER2-positive tumors.
The results of this kind of study are coming out slowly and quietly and indicate that taxol containing regimens didn't prolong survival over other more conventional and less expensive cytotoxic drugs. It may indeed give clincial response (tumor shrinkage), sometimes impressive, however, these are mostly short-lived and relapses after a response to taxanes (taxol) are often dramatic.
Even if one or more chemotherapy regimen is identified as being likely to work on a particular cancer, has the science advanced to tell us whether application of the chosen chemotherapy regimen will not cause other changes that also cause cancer to later return and perhaps be even harder to treat? Is it a case of chemotherapy being bad, in cases where it apparently works? Traditional chemotherapy is mutagenic (changes in form), you might kill off a whole lot of cancer, only to cause a mutation in the remaining cancer, such that the remaining cancer behaves in a more agressive fashion.
These studies tell us that much more work needs to be done, and oncologists need to adapt treatment to the patient. There are over 100 chemotherapeutic agents, all of which have approximately the same probability of working. The tumors of different patients have different responses to chemotherapy. It requires individualized treatment based on testing individual properties of each patient's cancer.
An editorial by Drs. V. Valero and G.N. Hortobagyi in the March 15, 2003 issue of the Journal of Clinical Oncology, reviewed all of the large, prospective, randomized trials published comparing taxane-based chemotherapy regimens. They conclude that none of these regimens have increased either complete response rates or overall survival, with median survivals remaining at two years or less, or precisely the same results which were being obtained over thirty years ago.
(J Clin Oncol 21(6): 959-962, '03)
A commentary by Dr. Lawrence N. Shulman, Vice Chair for Clinical Services and Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, in the September, 2002 issue of The American Journal of Oncology Review, describes the complete lack of progress in the chemotherapeutic treatment of metastatic breast cancer since 1970. Dr. Shulman noted that a retrospective comparision of a well-characterized "standard-dose" database with a less well-chaaracterized "high-dose" database suggested that there was increased early mortality for "high-dose" therapy.
(Am J Oncology Rev 1(3):169-170, '02) |
|
| Back to top |
|
|
|
gdpawel
Senior User
Joined: 15 Jan 2005
Posts: 123
Location: Pennsylvania
|
|
| Back to top |
|
|
|
mpd
New User
Joined: 15 May 2006
Posts: 1
Location: Florida
|
| Posted: Mon May 15, 2006 6:21 am Post subject: Carcinomatous Meningitis |
|
|
gdpawel,
I have a relative, who is a breast cancer patient, that has just been diagnosed with Carcinomatous Meningitis. Thank you for all the information you provided in your postings. Since it was last year since these postings, has there been any findings or breakthroughs on the treatment of CM? Any information would be extremely helpful. Thanks
_________________
mpd |
|
| Back to top |
|
|
|
|
Search 
Email Digests
Register to post
Profile 
Check private messages 
Log in
What is this ?
We subscribe to the HONcode principles. Verify here. All content and posts are copyright.
