Ovarian cancer and brain metastases
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.
Abstract
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.
http://www.ncbi.nlm.nih.gov/pubmed/20921883
Comments
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ASTRO: Brain Metastases Common in Ovarian Cancer
Brain metastases commonly develop among patients with ovarian cancer, and do so rapidly in those with advanced disease, a retrospective review found.
In a study of 78 women with ovarian cancer who developed one or more brain metastases, 50% developed a single metastasis, according to Sewit Teckie, MD, and colleagues from Memorial Sloan-Kettering Cancer Center in New York.
In addition to that group, another 19% of patients were found to have two or three metastases on initial diagnosis, 23% had four or more, and 8% already had leptomeningeal disease, Teckie told MedPage Today during a poster session at the annual meeting of the American Society for Radiation Oncology (ASTRO).
The patients were treated at the cancer center between 1983 and 2010. Their median age was 54.8 and 88% had stage III/IV disease.
The location of the metastases was the cerebral hemisphere in 56%, the cerebellum in 15%, and both in 28%.
Median overall survival was 62.3 months (95% CI 51.2 to 73.3).
The median time after diagnosis to the detection of brain metastasis was 71.1 months in patients with early-stage disease and 38.3 months when disease was diagnosed at stage III/IV.
Median follow-up for the entire cohort was eight months, and for the six patients still alive at the time of this analysis, median follow-up was 15 months.
Among all patients who developed the metastases, median subsequent survival was 8.9 months (95% CI 5.5 to 15.3), with a median survival of 14 months (95% CI 7.7 to 27.9) specifically in those who had only one metastasis.
A total of 92% of patients received whole- or partial-brain radiation therapy or stereotactic radiosurgery for their metastatic disease, while 49% had surgical treatment.
Most of those who had surgery had only one brain metastasis.
A total of 25 patients who underwent surgery also had postoperative radiation, and 15 required salvage radiation after local treatment was unsuccessful.
On multivariate analysis, these factors were associated with poor survival:
Karnofsky performance status ≥70, HR 0.35 (P=0.004)
Uncontrolled primary tumor, HR 1.81 (P=0.03)
Four or more brain metastases, HR 2.73 (P=0.002)
Leptomeningeal disease, HR 3.34 (P=0.01)
Among 33 of 39 patients for whom follow-up imaging was available, progressive or recurrent metastatic disease had occurred and 20.5% had developed leptomeningeal disease.
Six of those patients had an initial partial or complete response to radiotherapy, but two had later recurrences.
Median survival after radiation therapy for leptomeningeal disease was four months, although one patient remained alive after one year.
"More cases of leptomeningeal disease are being reported. These patients did better than patients usually do," Teckie said. "We knew leptomeningeal disease was a poor predictor, but this has not previously been analyzed statistically," she added.
In general, although brain metastases occur earlier in advanced ovarian cancer, if only one metastasis is present, stereotactic radiosurgery or surgery plus radiation therapy can provide a durable response and improve survival for some patients, she concluded.
Primary source: American Society for Radiation Oncology ASTRO 2011; Abstract 2568.
Source reference: Teckie S, et al "Predictors of survival in ovarian cancer brain metastases" ASTRO 2011; Abstract 2568.0 -
Am I correct in my understanding of your post that
as a result of Taxol use there is greater likelihood that a cancer will met to the brain?
Could you please post these two threads on the uterine board as our scans are usually "eyes to thighs"?
Thank you,
Claudia0 -
Taxol brain reactioncalifornia_artist said:Am I correct in my understanding of your post that
as a result of Taxol use there is greater likelihood that a cancer will met to the brain?
Could you please post these two threads on the uterine board as our scans are usually "eyes to thighs"?
Thank you,
Claudia
When I was in the ER last year with a bizarre brain reaction (staggering, stammering, blurred vision & unequal pupils), they fast-tracked me for a brain CT suspecting mets to my brain. Thankfully, the scan was negative but I was too shell shocked to refuse the taxol after that.
After the SECOND visit to the ER for the SAME symptoms, the doctor finally stopped giving me Taxol. I have to admit that I had a dramatic reduction in the tumor burden from the Taxol but couldn't convince the doctor to just decrease the dose.
I think some women are followed up with prolonged Taxol therapy as some oncologists understand the way Taxol disseminates tumor cells throughout the body. I think some women have a strong enough immune system to clean up after Taxol while others are not so fortunate.
What bothers me a lot is how second-line & subsequent chemos are chosen without any attempt at determining chemosensitivity for most of us. The attitude is "Let's see if this works and if it doesn't, we'll try something else as long as your bone marrow holds up." Ugh!0 -
I'm a poster child forLaundryQueen said:Taxol brain reaction
When I was in the ER last year with a bizarre brain reaction (staggering, stammering, blurred vision & unequal pupils), they fast-tracked me for a brain CT suspecting mets to my brain. Thankfully, the scan was negative but I was too shell shocked to refuse the taxol after that.
After the SECOND visit to the ER for the SAME symptoms, the doctor finally stopped giving me Taxol. I have to admit that I had a dramatic reduction in the tumor burden from the Taxol but couldn't convince the doctor to just decrease the dose.
I think some women are followed up with prolonged Taxol therapy as some oncologists understand the way Taxol disseminates tumor cells throughout the body. I think some women have a strong enough immune system to clean up after Taxol while others are not so fortunate.
What bothers me a lot is how second-line & subsequent chemos are chosen without any attempt at determining chemosensitivity for most of us. The attitude is "Let's see if this works and if it doesn't, we'll try something else as long as your bone marrow holds up." Ugh!
I'm a poster child for Taxol. I did 18 infusions of the stuff and tolerated it extremely well.
It is strong bug juice, for sure, but I agree...it doesn't agree with everyone and your doctors should have figured that out after the first ER visit.
Carlene0 -
Well, so far I have no brainHissy_Fitz said:I'm a poster child for
I'm a poster child for Taxol. I did 18 infusions of the stuff and tolerated it extremely well.
It is strong bug juice, for sure, but I agree...it doesn't agree with everyone and your doctors should have figured that out after the first ER visit.
Carlene
Well, so far I have no brain mets and all together I have has over 50 taxol infusions. Most of them were on the low dose schedule.0 -
taxane disseminationgdpawel said:ASTRO: Brain Metastases Common in Ovarian Cancer
Brain metastases commonly develop among patients with ovarian cancer, and do so rapidly in those with advanced disease, a retrospective review found.
In a study of 78 women with ovarian cancer who developed one or more brain metastases, 50% developed a single metastasis, according to Sewit Teckie, MD, and colleagues from Memorial Sloan-Kettering Cancer Center in New York.
In addition to that group, another 19% of patients were found to have two or three metastases on initial diagnosis, 23% had four or more, and 8% already had leptomeningeal disease, Teckie told MedPage Today during a poster session at the annual meeting of the American Society for Radiation Oncology (ASTRO).
The patients were treated at the cancer center between 1983 and 2010. Their median age was 54.8 and 88% had stage III/IV disease.
The location of the metastases was the cerebral hemisphere in 56%, the cerebellum in 15%, and both in 28%.
Median overall survival was 62.3 months (95% CI 51.2 to 73.3).
The median time after diagnosis to the detection of brain metastasis was 71.1 months in patients with early-stage disease and 38.3 months when disease was diagnosed at stage III/IV.
Median follow-up for the entire cohort was eight months, and for the six patients still alive at the time of this analysis, median follow-up was 15 months.
Among all patients who developed the metastases, median subsequent survival was 8.9 months (95% CI 5.5 to 15.3), with a median survival of 14 months (95% CI 7.7 to 27.9) specifically in those who had only one metastasis.
A total of 92% of patients received whole- or partial-brain radiation therapy or stereotactic radiosurgery for their metastatic disease, while 49% had surgical treatment.
Most of those who had surgery had only one brain metastasis.
A total of 25 patients who underwent surgery also had postoperative radiation, and 15 required salvage radiation after local treatment was unsuccessful.
On multivariate analysis, these factors were associated with poor survival:
Karnofsky performance status ≥70, HR 0.35 (P=0.004)
Uncontrolled primary tumor, HR 1.81 (P=0.03)
Four or more brain metastases, HR 2.73 (P=0.002)
Leptomeningeal disease, HR 3.34 (P=0.01)
Among 33 of 39 patients for whom follow-up imaging was available, progressive or recurrent metastatic disease had occurred and 20.5% had developed leptomeningeal disease.
Six of those patients had an initial partial or complete response to radiotherapy, but two had later recurrences.
Median survival after radiation therapy for leptomeningeal disease was four months, although one patient remained alive after one year.
"More cases of leptomeningeal disease are being reported. These patients did better than patients usually do," Teckie said. "We knew leptomeningeal disease was a poor predictor, but this has not previously been analyzed statistically," she added.
In general, although brain metastases occur earlier in advanced ovarian cancer, if only one metastasis is present, stereotactic radiosurgery or surgery plus radiation therapy can provide a durable response and improve survival for some patients, she concluded.
Primary source: American Society for Radiation Oncology ASTRO 2011; Abstract 2568.
Source reference: Teckie S, et al "Predictors of survival in ovarian cancer brain metastases" ASTRO 2011; Abstract 2568.
In stem cell research, anti-cancer treatments often effectively shrink the size of tumors, but some might have the opposite effect, actually expanding the small population of cancer stem cells that then are capable of metastasizing.
Using the CellSearch System technique that quantifies circulating tumor cells, scientists had shown that chemotherapy with Taxol causes a massive release of cells into the circulation, while at the same time reducing the size of the tumor, explaining that complete pathologic responses (tumor shrinkage) do not correlate well with improvements in survival.
Circulating tumor cells (CTCs) are cancer cells that have detached from solid tumors and entered the blood stream. This can begin the process of metastasis, the most life-threatening aspect of cancer. To metastasize, or spread cancer to other sites in the body, CTCs travel through the blood and can take root in another tissue or organ.
Even before the advent of the CellSearch technique, which was the "holy cow" moment about the dissemination after taxane-based chemotherapy, it had been observed in various cell-death assays, that there was an increase in the number of metabolic activity of mitochondria of the surviving cells from taxane therapy, even in cases where the majority of the cells are being killed by taxanes.
It may indeed give clincial response (tumor shrinkage), sometimes impressive, however, these are mostly short-lived and relapses after a response to taxanes are often dramatic.
Taxol actually causes cancer cell microtentacles (or extensions of the plasma membrane of cancer clles) to grow longer and allows tumor cells to reattach faster, appear to play a key role in how cancers spread to distant locations in the body.0 -
Personal Experiencegdpawel said:ASTRO: Brain Metastases Common in Ovarian Cancer
Brain metastases commonly develop among patients with ovarian cancer, and do so rapidly in those with advanced disease, a retrospective review found.
In a study of 78 women with ovarian cancer who developed one or more brain metastases, 50% developed a single metastasis, according to Sewit Teckie, MD, and colleagues from Memorial Sloan-Kettering Cancer Center in New York.
In addition to that group, another 19% of patients were found to have two or three metastases on initial diagnosis, 23% had four or more, and 8% already had leptomeningeal disease, Teckie told MedPage Today during a poster session at the annual meeting of the American Society for Radiation Oncology (ASTRO).
The patients were treated at the cancer center between 1983 and 2010. Their median age was 54.8 and 88% had stage III/IV disease.
The location of the metastases was the cerebral hemisphere in 56%, the cerebellum in 15%, and both in 28%.
Median overall survival was 62.3 months (95% CI 51.2 to 73.3).
The median time after diagnosis to the detection of brain metastasis was 71.1 months in patients with early-stage disease and 38.3 months when disease was diagnosed at stage III/IV.
Median follow-up for the entire cohort was eight months, and for the six patients still alive at the time of this analysis, median follow-up was 15 months.
Among all patients who developed the metastases, median subsequent survival was 8.9 months (95% CI 5.5 to 15.3), with a median survival of 14 months (95% CI 7.7 to 27.9) specifically in those who had only one metastasis.
A total of 92% of patients received whole- or partial-brain radiation therapy or stereotactic radiosurgery for their metastatic disease, while 49% had surgical treatment.
Most of those who had surgery had only one brain metastasis.
A total of 25 patients who underwent surgery also had postoperative radiation, and 15 required salvage radiation after local treatment was unsuccessful.
On multivariate analysis, these factors were associated with poor survival:
Karnofsky performance status ≥70, HR 0.35 (P=0.004)
Uncontrolled primary tumor, HR 1.81 (P=0.03)
Four or more brain metastases, HR 2.73 (P=0.002)
Leptomeningeal disease, HR 3.34 (P=0.01)
Among 33 of 39 patients for whom follow-up imaging was available, progressive or recurrent metastatic disease had occurred and 20.5% had developed leptomeningeal disease.
Six of those patients had an initial partial or complete response to radiotherapy, but two had later recurrences.
Median survival after radiation therapy for leptomeningeal disease was four months, although one patient remained alive after one year.
"More cases of leptomeningeal disease are being reported. These patients did better than patients usually do," Teckie said. "We knew leptomeningeal disease was a poor predictor, but this has not previously been analyzed statistically," she added.
In general, although brain metastases occur earlier in advanced ovarian cancer, if only one metastasis is present, stereotactic radiosurgery or surgery plus radiation therapy can provide a durable response and improve survival for some patients, she concluded.
Primary source: American Society for Radiation Oncology ASTRO 2011; Abstract 2568.
Source reference: Teckie S, et al "Predictors of survival in ovarian cancer brain metastases" ASTRO 2011; Abstract 2568.
I'm not big on research and stats. (I'm not impugning your knowledge or your experience,I'm so sorry for the loss you experienced and I'm grateful for your knowledge and the fact that you share it with all of us. I just feel that it's important to provide a little personal perspective and hope).
When I was diagnosed with brain mets, after being in remission for all of us 9 months, I was devastated. My neurosurgeon and radiation oncologist at University of Maryland gave me a great deal of hope, however. I was informed that I had three lesions. The largest of the three was removed with surgery, the others were shrunk with whole brain radiation and then eradicated with Gamma Knife. I am currently cancer free. My doctors have told me that there is very little chance (10%) that my cancer will return in the brain again. I'm liking those odds and planning to stick around for a few more decades.
Leesa0 -
Another Personal Experienceleesag said:Personal Experience
I'm not big on research and stats. (I'm not impugning your knowledge or your experience,I'm so sorry for the loss you experienced and I'm grateful for your knowledge and the fact that you share it with all of us. I just feel that it's important to provide a little personal perspective and hope).
When I was diagnosed with brain mets, after being in remission for all of us 9 months, I was devastated. My neurosurgeon and radiation oncologist at University of Maryland gave me a great deal of hope, however. I was informed that I had three lesions. The largest of the three was removed with surgery, the others were shrunk with whole brain radiation and then eradicated with Gamma Knife. I am currently cancer free. My doctors have told me that there is very little chance (10%) that my cancer will return in the brain again. I'm liking those odds and planning to stick around for a few more decades.
Leesa
Leesa
I sincerely appreciate your personal experience. Aside from research and stats, here is a little personal perspective from the other side. When my wife was diagnosed with a solitary brain met, 11 months after receiving Taxol + Carboplatin treatment, the 3.5cm tumor was excised and she received 5 fractions (1000 cGy) of focal radiation to the local tumor bed, plus 20 fractions (4000 cGy) of whole brain radiation over a 35 day period.
Recurrence of the cerebral metastasis was observed 21 months afterwards, with 4 mm-sized metastatic tumors in and around the previously resected and radiated cerebeller tumor. Because of her weakened condition from whole brain radiation, Gamma-Knife treatment was the best treatment option (although she did not survive much after it). With a very little chance (10%) of cancer returning in the brain again, I'm not big on statistics either. So much for whole brain radiation. Best wishes!
Greg0 -
Hi Greg,gdpawel said:Another Personal Experience
Leesa
I sincerely appreciate your personal experience. Aside from research and stats, here is a little personal perspective from the other side. When my wife was diagnosed with a solitary brain met, 11 months after receiving Taxol + Carboplatin treatment, the 3.5cm tumor was excised and she received 5 fractions (1000 cGy) of focal radiation to the local tumor bed, plus 20 fractions (4000 cGy) of whole brain radiation over a 35 day period.
Recurrence of the cerebral metastasis was observed 21 months afterwards, with 4 mm-sized metastatic tumors in and around the previously resected and radiated cerebeller tumor. Because of her weakened condition from whole brain radiation, Gamma-Knife treatment was the best treatment option (although she did not survive much after it). With a very little chance (10%) of cancer returning in the brain again, I'm not big on statistics either. So much for whole brain radiation. Best wishes!
Greg
I understand your
Hi Greg,
I understand your perspective entirely, words cannot express how sorry I am for your loss. This cancer is so unfair and unpredictable. I truly appreciate everything you post to help OVCA patients and their families.
Hugs and prayers,
Leesa0 -
Terraingdpawel said:ASTRO: Brain Metastases Common in Ovarian Cancer
Brain metastases commonly develop among patients with ovarian cancer, and do so rapidly in those with advanced disease, a retrospective review found.
In a study of 78 women with ovarian cancer who developed one or more brain metastases, 50% developed a single metastasis, according to Sewit Teckie, MD, and colleagues from Memorial Sloan-Kettering Cancer Center in New York.
In addition to that group, another 19% of patients were found to have two or three metastases on initial diagnosis, 23% had four or more, and 8% already had leptomeningeal disease, Teckie told MedPage Today during a poster session at the annual meeting of the American Society for Radiation Oncology (ASTRO).
The patients were treated at the cancer center between 1983 and 2010. Their median age was 54.8 and 88% had stage III/IV disease.
The location of the metastases was the cerebral hemisphere in 56%, the cerebellum in 15%, and both in 28%.
Median overall survival was 62.3 months (95% CI 51.2 to 73.3).
The median time after diagnosis to the detection of brain metastasis was 71.1 months in patients with early-stage disease and 38.3 months when disease was diagnosed at stage III/IV.
Median follow-up for the entire cohort was eight months, and for the six patients still alive at the time of this analysis, median follow-up was 15 months.
Among all patients who developed the metastases, median subsequent survival was 8.9 months (95% CI 5.5 to 15.3), with a median survival of 14 months (95% CI 7.7 to 27.9) specifically in those who had only one metastasis.
A total of 92% of patients received whole- or partial-brain radiation therapy or stereotactic radiosurgery for their metastatic disease, while 49% had surgical treatment.
Most of those who had surgery had only one brain metastasis.
A total of 25 patients who underwent surgery also had postoperative radiation, and 15 required salvage radiation after local treatment was unsuccessful.
On multivariate analysis, these factors were associated with poor survival:
Karnofsky performance status ≥70, HR 0.35 (P=0.004)
Uncontrolled primary tumor, HR 1.81 (P=0.03)
Four or more brain metastases, HR 2.73 (P=0.002)
Leptomeningeal disease, HR 3.34 (P=0.01)
Among 33 of 39 patients for whom follow-up imaging was available, progressive or recurrent metastatic disease had occurred and 20.5% had developed leptomeningeal disease.
Six of those patients had an initial partial or complete response to radiotherapy, but two had later recurrences.
Median survival after radiation therapy for leptomeningeal disease was four months, although one patient remained alive after one year.
"More cases of leptomeningeal disease are being reported. These patients did better than patients usually do," Teckie said. "We knew leptomeningeal disease was a poor predictor, but this has not previously been analyzed statistically," she added.
In general, although brain metastases occur earlier in advanced ovarian cancer, if only one metastasis is present, stereotactic radiosurgery or surgery plus radiation therapy can provide a durable response and improve survival for some patients, she concluded.
Primary source: American Society for Radiation Oncology ASTRO 2011; Abstract 2568.
Source reference: Teckie S, et al "Predictors of survival in ovarian cancer brain metastases" ASTRO 2011; Abstract 2568.
So, this comment will likely fly in the face of the medical perspective, but if one accepts that cancer is a systemic disease and not a disease of the organs, then it would seem that altering the terrain of the body would reduce the likelihood that cancer cells released into the blood stream from Taxol treatment would grow elsewhere in the body. I personally know people with tumors in their bodies, who keep them controlled with a specific type of diet, exercise, stress management, supplements, etc. If they can keep a full-sized tumor at bay, I would think the same practices would neutralize the ciruculating tumor cells released by Taxol.0 -
Oopsgdpawel said:ASTRO: Brain Metastases Common in Ovarian Cancer
Brain metastases commonly develop among patients with ovarian cancer, and do so rapidly in those with advanced disease, a retrospective review found.
In a study of 78 women with ovarian cancer who developed one or more brain metastases, 50% developed a single metastasis, according to Sewit Teckie, MD, and colleagues from Memorial Sloan-Kettering Cancer Center in New York.
In addition to that group, another 19% of patients were found to have two or three metastases on initial diagnosis, 23% had four or more, and 8% already had leptomeningeal disease, Teckie told MedPage Today during a poster session at the annual meeting of the American Society for Radiation Oncology (ASTRO).
The patients were treated at the cancer center between 1983 and 2010. Their median age was 54.8 and 88% had stage III/IV disease.
The location of the metastases was the cerebral hemisphere in 56%, the cerebellum in 15%, and both in 28%.
Median overall survival was 62.3 months (95% CI 51.2 to 73.3).
The median time after diagnosis to the detection of brain metastasis was 71.1 months in patients with early-stage disease and 38.3 months when disease was diagnosed at stage III/IV.
Median follow-up for the entire cohort was eight months, and for the six patients still alive at the time of this analysis, median follow-up was 15 months.
Among all patients who developed the metastases, median subsequent survival was 8.9 months (95% CI 5.5 to 15.3), with a median survival of 14 months (95% CI 7.7 to 27.9) specifically in those who had only one metastasis.
A total of 92% of patients received whole- or partial-brain radiation therapy or stereotactic radiosurgery for their metastatic disease, while 49% had surgical treatment.
Most of those who had surgery had only one brain metastasis.
A total of 25 patients who underwent surgery also had postoperative radiation, and 15 required salvage radiation after local treatment was unsuccessful.
On multivariate analysis, these factors were associated with poor survival:
Karnofsky performance status ≥70, HR 0.35 (P=0.004)
Uncontrolled primary tumor, HR 1.81 (P=0.03)
Four or more brain metastases, HR 2.73 (P=0.002)
Leptomeningeal disease, HR 3.34 (P=0.01)
Among 33 of 39 patients for whom follow-up imaging was available, progressive or recurrent metastatic disease had occurred and 20.5% had developed leptomeningeal disease.
Six of those patients had an initial partial or complete response to radiotherapy, but two had later recurrences.
Median survival after radiation therapy for leptomeningeal disease was four months, although one patient remained alive after one year.
"More cases of leptomeningeal disease are being reported. These patients did better than patients usually do," Teckie said. "We knew leptomeningeal disease was a poor predictor, but this has not previously been analyzed statistically," she added.
In general, although brain metastases occur earlier in advanced ovarian cancer, if only one metastasis is present, stereotactic radiosurgery or surgery plus radiation therapy can provide a durable response and improve survival for some patients, she concluded.
Primary source: American Society for Radiation Oncology ASTRO 2011; Abstract 2568.
Source reference: Teckie S, et al "Predictors of survival in ovarian cancer brain metastases" ASTRO 2011; Abstract 2568.
Double post. Read the next one.0 -
Ovarian Cancer Therapyclynn13 said:Well, so far I have no brain
Well, so far I have no brain mets and all together I have has over 50 taxol infusions. Most of them were on the low dose schedule.
Dr. Nagourney is medical and laboratory director at Rational Therapeutics, Inc., in Long Beach, California, and an instructor of Pharmacology at the University of California, Irvine School of Medicine. He is board-certified in Internal Medicine, Medical Oncology and Hematology. He blogged recently about the so-called "standard" treatment for ovarian cancer:
"I watched with interest as the GOG 182 five-arm clinical trial unfolded. This international study of over 4,000 patients randomly mixed and matched drug combinations but provided no evidence of superiority of one arm over another. The final conclusion of the manuscript that reported these results (Bookman, MA., Brady, MF, McGuire, WP, et al. J Clin Oncol 27: 1419-1425, 2009), stipulated that carboplatin plus taxol remained the “gold standard” for advanced epithelial ovarian carcinoma. A study of over 900 patients that compared carboplatin plus gemcitabine to carboplatin plus paclitaxel induction (Gordon A, Teneriello M, Lim, P, et al Clinical Ovarian Cancer, 2, 2:99-105, 2009) again provided comparable outcomes between arms yet carboplatin plus taxol remains the “gold standard.”
To this collection of published experiences, we now add the report by Sandro Pignata and co-investigators from the MITO-2 Phase III trial (Pignata, S., Scambia, G., Ferrandina, G., et al. J Clin Oncol 29: 3628-3635, 2011). This clinical trial conducted by Italian investigators compared carboplatin plus taxol to carboplatin plus pegylated liposomal doxorubicin (PLD) known in the U.S. as Doxil. Four hundred and ten patients were randomized to each arm of the trial. The results revealed numerical superiority for the carboplatin plus PLD arm in terms of median progression-free survival (19 months vs. 16.8 months) and numerical superiority for overall survival for the carboplatin plus PLD over the carboplatin plus taxol arm (61.6 vs. 53.2 months). However, these results did not achieve statistical significance. Therefore, the authors conclude that carboplatin plus taxol “remains the standard first-line chemotherapy for ovarian cancer.” While they do grant that, based on toxicity, carboplatin plus PLD could be considered as an alternative therapy.
With the GOG 182 study, the Gordon study (comparing carboplatin plus gemcitabine) and the most recent Pignata study comparing carboplatin plus PLD all establishing activity for several first-line regimens, why is it that the gynecologic oncologists continually return to carboplatin plus taxol as the “gold standard?”
Is there not ample evidence that several regimens provide similar results and survivals? Is there not evidence that the toxicities differ? Why can’t the gynecologic oncologists get off the dime? Why can’t they admit that several treatment regimens are appropriate and indicated for the malignancy? Why can’t they admit that some patients may, in fact, do better with one treatment over another?
I may add, it’s never been shown that adding paclitaxel (Taxol) to first line treatment of ovarian cancer improved survival. It’s been shown that paclitaxel + platinum is superior to paclitaxel + cyclophosphamide. It’s never been shown that paclitaxel + platinum is superior to single agent cisplatin or carboplatin.
The findings in the GOG 132 study and the International Collaborative Ovarian Neoplasm study (ICON3) of equivalent effectiveness with the initial use of single-agent platin compared with platin-taxane doublets, the issue of whether the combination of platin and paclitaxel is superior to initial single-agent platin is still unresolved. First-line comparative studies have demonstrated equivalent effectiveness.
Muggia FM, Braly PS, Brady MF, et al: Phase III randomized study of cisplatin versus paclitaxel versus cisplatin and paclitaxel in patients with suboptimal stage III or IV ovarian cancer: A Gynecologic Oncology Group study. J Clin Oncol 18:106-115, 2000
The International Collaborative Ovarian Neoplasm (ICON) Group: Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: The ICON3 randomised trial. Lancet 360:505-515, 2002
Source: JCO, Vol 27, No. 9, March 20, 20090 -
greg,gdpawel said:Ovarian Cancer Therapy
Dr. Nagourney is medical and laboratory director at Rational Therapeutics, Inc., in Long Beach, California, and an instructor of Pharmacology at the University of California, Irvine School of Medicine. He is board-certified in Internal Medicine, Medical Oncology and Hematology. He blogged recently about the so-called "standard" treatment for ovarian cancer:
"I watched with interest as the GOG 182 five-arm clinical trial unfolded. This international study of over 4,000 patients randomly mixed and matched drug combinations but provided no evidence of superiority of one arm over another. The final conclusion of the manuscript that reported these results (Bookman, MA., Brady, MF, McGuire, WP, et al. J Clin Oncol 27: 1419-1425, 2009), stipulated that carboplatin plus taxol remained the “gold standard” for advanced epithelial ovarian carcinoma. A study of over 900 patients that compared carboplatin plus gemcitabine to carboplatin plus paclitaxel induction (Gordon A, Teneriello M, Lim, P, et al Clinical Ovarian Cancer, 2, 2:99-105, 2009) again provided comparable outcomes between arms yet carboplatin plus taxol remains the “gold standard.”
To this collection of published experiences, we now add the report by Sandro Pignata and co-investigators from the MITO-2 Phase III trial (Pignata, S., Scambia, G., Ferrandina, G., et al. J Clin Oncol 29: 3628-3635, 2011). This clinical trial conducted by Italian investigators compared carboplatin plus taxol to carboplatin plus pegylated liposomal doxorubicin (PLD) known in the U.S. as Doxil. Four hundred and ten patients were randomized to each arm of the trial. The results revealed numerical superiority for the carboplatin plus PLD arm in terms of median progression-free survival (19 months vs. 16.8 months) and numerical superiority for overall survival for the carboplatin plus PLD over the carboplatin plus taxol arm (61.6 vs. 53.2 months). However, these results did not achieve statistical significance. Therefore, the authors conclude that carboplatin plus taxol “remains the standard first-line chemotherapy for ovarian cancer.” While they do grant that, based on toxicity, carboplatin plus PLD could be considered as an alternative therapy.
With the GOG 182 study, the Gordon study (comparing carboplatin plus gemcitabine) and the most recent Pignata study comparing carboplatin plus PLD all establishing activity for several first-line regimens, why is it that the gynecologic oncologists continually return to carboplatin plus taxol as the “gold standard?”
Is there not ample evidence that several regimens provide similar results and survivals? Is there not evidence that the toxicities differ? Why can’t the gynecologic oncologists get off the dime? Why can’t they admit that several treatment regimens are appropriate and indicated for the malignancy? Why can’t they admit that some patients may, in fact, do better with one treatment over another?
I may add, it’s never been shown that adding paclitaxel (Taxol) to first line treatment of ovarian cancer improved survival. It’s been shown that paclitaxel + platinum is superior to paclitaxel + cyclophosphamide. It’s never been shown that paclitaxel + platinum is superior to single agent cisplatin or carboplatin.
The findings in the GOG 132 study and the International Collaborative Ovarian Neoplasm study (ICON3) of equivalent effectiveness with the initial use of single-agent platin compared with platin-taxane doublets, the issue of whether the combination of platin and paclitaxel is superior to initial single-agent platin is still unresolved. First-line comparative studies have demonstrated equivalent effectiveness.
Muggia FM, Braly PS, Brady MF, et al: Phase III randomized study of cisplatin versus paclitaxel versus cisplatin and paclitaxel in patients with suboptimal stage III or IV ovarian cancer: A Gynecologic Oncology Group study. J Clin Oncol 18:106-115, 2000
The International Collaborative Ovarian Neoplasm (ICON) Group: Paclitaxel plus carboplatin versus standard chemotherapy with either single-agent carboplatin or cyclophosphamide, doxorubicin, and cisplatin in women with ovarian cancer: The ICON3 randomised trial. Lancet 360:505-515, 2002
Source: JCO, Vol 27, No. 9, March 20, 2009
there is indirect
greg,
there is indirect evidence that Taxol does have additive value to single agent carboplatin.
The Japanese dose dense regiment yield an amazing PFS and OS benefit. Note that the scheduling changes were done for TAXOL only. Carbo was still administered on a 3 week schedule. This is an indirect evidence that taxol does something, and when an optimum schedule was used for taxol infusion, the patients benefited greatly. If taxol played no role, chancing taxol administration would not have yield any improvement.0 -
double postTethys41 said:Terrain
So, this comment will likely fly in the face of the medical perspective, but if one accepts that cancer is a systemic disease and not a disease of the organs, then it would seem that altering the terrain of the body would reduce the likelihood that cancer cells released into the blood stream from Taxol treatment would grow elsewhere in the body. I personally know people with tumors in their bodies, who keep them controlled with a specific type of diet, exercise, stress management, supplements, etc. If they can keep a full-sized tumor at bay, I would think the same practices would neutralize the ciruculating tumor cells released by Taxol.
double post0 -
CuriousTethys41 said:Terrain
So, this comment will likely fly in the face of the medical perspective, but if one accepts that cancer is a systemic disease and not a disease of the organs, then it would seem that altering the terrain of the body would reduce the likelihood that cancer cells released into the blood stream from Taxol treatment would grow elsewhere in the body. I personally know people with tumors in their bodies, who keep them controlled with a specific type of diet, exercise, stress management, supplements, etc. If they can keep a full-sized tumor at bay, I would think the same practices would neutralize the ciruculating tumor cells released by Taxol.
Are you also controlling your tumors with diet, exercise, stress management and supplements?
So far, I've found medical science, surgery and other medical interventions to be successful.0 -
Currently NEDleesag said:Curious
Are you also controlling your tumors with diet, exercise, stress management and supplements?
So far, I've found medical science, surgery and other medical interventions to be successful.
Leesa,
I am currently NED, but am practicing the same lifestyle guidelines as those who do control their tumors, in order to stay NED as long as possible.0 -
Additive vs Synergisticevertheoptimist said:greg,
there is indirect
greg,
there is indirect evidence that Taxol does have additive value to single agent carboplatin.
The Japanese dose dense regiment yield an amazing PFS and OS benefit. Note that the scheduling changes were done for TAXOL only. Carbo was still administered on a 3 week schedule. This is an indirect evidence that taxol does something, and when an optimum schedule was used for taxol infusion, the patients benefited greatly. If taxol played no role, chancing taxol administration would not have yield any improvement.
ETO
Sometimes drug "combinations" have merely an "additive" anti-tumor effect and do not produce a "synergistic" (cooperative) effect. Additive is where the whole equals the sum of its parts. Synergy is defined as supra-additivity wherein the whole is greater than the sum of the parts, which reflects an elegant interaction between drugs predicated on their modes of action.
You'd want a drug combination to produce a synergistic effect and not merely an additive anti-tumor effect, or resistant to an "individual's" tumor cells. You really want to take advantage of the synergy between "effective" drug combinations.
In cell function analysis, Taxol has been found to be a drug with a below average probability of providing clinical benefit, based on the fact that taxanes are almost never synergistic with platinums, but only additive.
Clinical oncologists using cell-based assays have found out that the combination of Gemzar + Platinum (either Cisplatin, Carboplatin or Oxaliplatin) is about the most important drug "combination" introduced for the treatment of solid tumors in the past twenty years. Clinical responses to real-time assay analysis with this regimen are unprecedented.
Cell culture assays had contributed, in terms of recognizing the synergistic effects of this combination, in getting clinical trials with this regimen started in a broad spectrum of cancers, including ovarian.0 -
ah... greg,gdpawel said:Additive vs Synergistic
ETO
Sometimes drug "combinations" have merely an "additive" anti-tumor effect and do not produce a "synergistic" (cooperative) effect. Additive is where the whole equals the sum of its parts. Synergy is defined as supra-additivity wherein the whole is greater than the sum of the parts, which reflects an elegant interaction between drugs predicated on their modes of action.
You'd want a drug combination to produce a synergistic effect and not merely an additive anti-tumor effect, or resistant to an "individual's" tumor cells. You really want to take advantage of the synergy between "effective" drug combinations.
In cell function analysis, Taxol has been found to be a drug with a below average probability of providing clinical benefit, based on the fact that taxanes are almost never synergistic with platinums, but only additive.
Clinical oncologists using cell-based assays have found out that the combination of Gemzar + Platinum (either Cisplatin, Carboplatin or Oxaliplatin) is about the most important drug "combination" introduced for the treatment of solid tumors in the past twenty years. Clinical responses to real-time assay analysis with this regimen are unprecedented.
Cell culture assays had contributed, in terms of recognizing the synergistic effects of this combination, in getting clinical trials with this regimen started in a broad spectrum of cancers, including ovarian.
you can't have
ah... greg,
you can't have it both ways. You stated above that taxol has hardly any added benefit to carbo, not even additive value. Now, you are saying, it has additive value, but still not good enough since it does not have synergistic value. I am not challenging you with the additive vs. synergistic. I was simply providing a different perspective to your statement earlier that taxol does not add much benefit.
The dose dense study produced amazingly significant outcome (PFS difference of 11 months!!!! - this is the best outcome I have EVER seen in all the studies I read so far), and that amazing PFS difference was SOLELY attributed to the variation in Taxol drug delivery schedule. If Taxol had not had such an important role in this regimen, tinkering with its delivery schedule should NOT have produced this kind of unprecedented study outcome. People can say all they want about Taxol' lack of effectivess. However, until somebody comes up with an alternative explanation of how this clinical study outcome could have happened while discounting the singular role of Taxol in this case, I will have hard time believing the argument.0 -
Not going to split hairsevertheoptimist said:ah... greg,
you can't have
ah... greg,
you can't have it both ways. You stated above that taxol has hardly any added benefit to carbo, not even additive value. Now, you are saying, it has additive value, but still not good enough since it does not have synergistic value. I am not challenging you with the additive vs. synergistic. I was simply providing a different perspective to your statement earlier that taxol does not add much benefit.
The dose dense study produced amazingly significant outcome (PFS difference of 11 months!!!! - this is the best outcome I have EVER seen in all the studies I read so far), and that amazing PFS difference was SOLELY attributed to the variation in Taxol drug delivery schedule. If Taxol had not had such an important role in this regimen, tinkering with its delivery schedule should NOT have produced this kind of unprecedented study outcome. People can say all they want about Taxol' lack of effectivess. However, until somebody comes up with an alternative explanation of how this clinical study outcome could have happened while discounting the singular role of Taxol in this case, I will have hard time believing the argument.
Not going to split hairs here. You want a drug combination to produce a synergistic effect and not merely an additive effect. You want to take advantage of the "synergy" (cooperation) between "effective" drug combinations. Taxanes are almost never synergistic with platinums. What makes Gemzar + Platinum so successful is the synergistic effects of this combination.
The dose-dense protocol gives the drug more often, but not at a "lower" dose. Dose-dense chemotherapy shortens the treatment cycle while maintaining roughly the same chemotherapy dosage as conventional chemotherapy (the process reduction of time gap between two regular doses).
Dose-dense treatment is usually given with breaks of several weeks between doses to let the body try to recover. However, the anti-angiogenic effects of dose-dense therapy is masked and marginalized by administering it this way.
Low-dose chemotherapy not only shortens the treatment cycle but "lowers" the dosage of treatment a patient can withstand during shorten administration of "any" conventional drugs.
The main targets of dose-dense chemotherapy are proliferating tumor cells. The main targets of low-dose chemotherapy are the endothelial cells of the growing vasculature of a tumor. In other words (any) chemotherapeutics can be used as anti-angiogenic agents.
Blood vessel cells are less likely than tumor cells to become resistant to chemotherapy, so if cancer cells become drug resistant, these drugs should still be able to shrink tumors by destroying their blood supply.
Since the endothelial cells (involved in angiogenesis) are the first in the tumor to undergo cell death (apoptosis), the more frequent, and lower-dose therapy can have an impressive anti-angiogenic and anti-tumor effects.0 -
Appreciation for informationevertheoptimist said:ah... greg,
you can't have
ah... greg,
you can't have it both ways. You stated above that taxol has hardly any added benefit to carbo, not even additive value. Now, you are saying, it has additive value, but still not good enough since it does not have synergistic value. I am not challenging you with the additive vs. synergistic. I was simply providing a different perspective to your statement earlier that taxol does not add much benefit.
The dose dense study produced amazingly significant outcome (PFS difference of 11 months!!!! - this is the best outcome I have EVER seen in all the studies I read so far), and that amazing PFS difference was SOLELY attributed to the variation in Taxol drug delivery schedule. If Taxol had not had such an important role in this regimen, tinkering with its delivery schedule should NOT have produced this kind of unprecedented study outcome. People can say all they want about Taxol' lack of effectivess. However, until somebody comes up with an alternative explanation of how this clinical study outcome could have happened while discounting the singular role of Taxol in this case, I will have hard time believing the argument.
Ever,
I can't speak for everyone here, but I deeply appreciate the information Greg regularly posts here. Just as with the information my doctor shares with me, if I have a question regarding Greg's information, I will ask him about it. If I'm still not comfortable with it, I will do further research. I have seen your posts over on the Uterine cancer board. I spent a few short weeks posting over there until the confrontational, "I'm right/you're wrong" attitude discouraged me from continuing to visit over there. Not saying you're one oof them. As with any member here on the Ovarian cancer board, feel free to ask questions, but please do not make this into an all or nothing debate. People on the Uterine board miss out on a lot of beneficial information that is out there because a few members are contrary and combative. Please do not discourage our helpful resources on this board.0
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