Oct 22, 2011 - 1:24 pm
The mechanisms by which primary tumors produce brain metastases is thought to be hematogenous (blood) spread from primary or secondary sites in the lung. Since the brain has no lymphatic system, all tumors metastasizing to the brain do so by spreading through the bloodstream. Arterial blood passes through the lungs before entering the brain, and collects tumor cells filtered out in capillaries, which subsequently embolize to the brain.
The jury is out on how ovarian cancer spreads. As less is known about this disease than other cancers this has not been definitively answered and there is controversy among the ranks of researchers and clinicians. Many believe it does not spread via the lymph and spreads through cells shedding into ascites in the absominal cavity and then seeding in distant sites. It does spread this way but is probably not the only way as it is found in lymph nodes as well.
There are essentially four ways that ovarian cancer metastasis takes place.
1. The first has to do with direct contact with the tumor itself. The tumor invades nearby organs, such as the uterus, bladder, or fallopian tubes.
2. Ovarian cancer can spread by what is known as seeding. This is shedding cancer cells into the abdominal cavity. These cells can then attach to the liver, colon, or stomach and begin to proliferate. This scattering process can make it possible to infect several different key organs.
3. Ovarian cancer metastasis can involve portions of the tumor breaking off and invading the lymphatic system. The collections of cancerous cells are then transported to distant organs, such as the lungs, where new tumors form and grow.
4. Ovarian cancer cells can travel through the bloodstream to other areas of the body, where they develop into various types of cancer.
It has long been believed that it does not metastasize to the brain - however in recent years - women living longer are developing brain mets. One school of thought believes that platinum and taxane drugs maybe weakening the blood brain barrier but that does not explain every instance.
Ovarian cancer uncommonly involves the central nervous system. Brain metastasis were a rare complication of ovarian cancer with only 67 well-documented cases in medical literature until 1994, according to the National Cancer Institute. 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%. Even more rare was the occurrance of Leptomeningeal Carcinomatous or Carcinomatous Meningitis. Until 1994, there have been only 14 cases reported. This presentation is similar to metastases from other solid tumors (breast, lung).
In a study by Christos Kosmas, M.D., consultant medical oncologist, Department of Medicine and Medical Oncology Unit at Helena-Venizelou Hospital, Athens, Greece entitled, "Carcinomatous Meningitis: Taxane-Induced," which found what is called "dissemination after taxane-based (Taxol) chemotherapy." The study conclusions stated that Carcinomatous Meningitis (a CNS metastasis) after a major response to front-line taxane-based regimens represents a grave disease manifestation and its incidence appears increased when compared retrospectively to non-taxane-treated patients http://cancerfocus.org/forum/showthread.php?t=2871
During the past fifteen years it has been frequently observed that more and more patients were presenting central nervous system (CNS) involvement as the only evidence of disease progression. It seems that retrospective studies in patients with epithelial ovarian cancer do not differ among patients who relapsed with isolated brain metastases and those with relapse outside the CNS.
The trafficking of cancer cells to their final destination may be guided by factors produced by stromal cells of their host organ. For example, Melanoma cells are closely related to CNS cells. Breast cancer cells more commonly are found in the posterior pituitary. Renal, gastrointestinal and pelvic are cancers tend to metastasize to the cerebellum.
Brain metastases, unfortunately are very common and grave condition in the natural history of patients with cancer. It is estimated that approximately 250,000 patients with cancer will develop brain metastasis in the United States each year. Autopsy data have shown that up to 50% of patients who die with cancer have evidence of spread to the central nervous system, with approximately 40% of these patients having a solitary or single metastasis.
Solitary means that this metastasis is the only evidence of cancer in the whole body, whereas single means that there are other deposits of cancer outside the brain. Tumors more prone to brain dissemination are Lung, Breast, Melanoma, Renal Cell Carcinoma, Colorectal and Sarcoma.
Metastases are defined as the appearance of neoplasms in parts of the body remote from the site of the primary tumor. Metastasis can occur through one of three processes: direct seeding of body cavities or surfaces, lymphatic spread, and hematogenous spread.
Distant metastasis via the bloodstream may affect virtually any organ. The lungs, bones, liver, and adrenals are the most common of metastasis. In order for metastasis to occur, tumor cells must break free from the primary mass, enter the lymphatics or bloodstream, and produce a secondary growth at a distant site.
Although millions of cells are released into the circulation each day from a one primary tumor, few actually survive. Factors determining the success of metastasis include surface attachment, hormones, blood supply, and the body's own immunity.
Approximately 30% of intracranial tumors are metastases. The most common primary sites for these metastases are the lung, breast, skin, kidney, and gastrointestinal tract. Carcinomatous meningitis, a condition resulting in widespread dissemination of carcinoma in the meninges, is particularly associated with small cell carcinoma of the lung, adenocarcinoma of the lung, and carcinoma of the breast.
It doesn't mention anything about ovarian cancer. I was shocked to find out the studies about Taxol!
An article in Gynecologic Oncology (Volume 92, Issue 3, March 2004, Pages 978-980) by John P. Micha, et al, Gynecologic Oncology Associates, Hoag Memorial Hospital Cancer Center, Newport Beach, CA states that brain metastases resulting from primary ovarian cancer are rare, however, there have been recent studies suggesting an increased incidence of brain metastases (PubMed PMID: 14984970).
Am J Clin Oncol. 2010 Oct 1.
Multidrug Resistance Gene (MDR-1) and Risk of Brain Metastasis in Epithelial Ovarian, Fallopian Tube, and Peritoneal Cancer.
Matsuo K, Eno ML, Ahn EH, Shahzad MM, Im DD, Rosenshein NB, Sood AK.
BACKGROUND: To evaluate risk factors that predict brain metastasis in epithelial ovarian, fallopian tube, and peritoneal cancer.
METHODS: All patients with FIGO stage I to IV who underwent initial cytoreductive surgery between January 1995 and January 2009 were evaluated. The tumor samples were evaluated for 7 markers including multidrug resistance gene (MDR-1), DNA aneuploidity and S-phase fraction, human epidermal growth factor receptor 2, estrogen receptor, progesterone receptor, p53 mutation, epidermal growth factor receptor, and CD31. Biomarker expression was evaluated as a predictor of hematogenous metastasis to the following locations: (i) liver and spleen, (ii) lung, and (iii) brain.
RESULTS: There were 309 cases identified during the period. Of those, 5 (1.6%, 95% CI: 0.2%-3.0%) women developed brain metastasis. Time to onset of brain metastasis was significantly longer than that for other recurrent sites (median time to recurrence after initial cytoreduction, brain vs. lung vs. liver, 21.4 vs. 12.6 vs. 11.0 months, P < 0.05). Significantly increased expression of MDR-1 was seen in tumors from women who developed brain metastasis (brain vs. nonbrain sites, 80% vs. 4.2%-24.3%, P = 0.004). In multivariate analysis, MDR-1 was the only significant variable associated with the risk of brain metastasis. MDR-1 expression predicted brain metastasis (receiver-operator-characteristic curve analysis, AUC 0.808, P = 0.018), and with a 10% positive expression of MDR-1 as the cutoff value, sensitivity, specificity, positive predictive value, negative predictive value, accuracy of prediction of brain metastasis were 80%, 86.1%, 15.4%, 99.3%, and 85.9%, respectively (odds ratio: 24.7, 95% CI: 2.64-232, P = 0.002).
CONCLUSIONS: Increased expression of MDR-1 in the tumor tissue obtained at initial cytoreduction is associated with increased risk of developing brain metastases in women with epithelial ovarian, fallopian tube, or peritoneal cancer.