ScienceDirect.com - Gynecologic Oncology - Hormonal therapy for recurrent low-grade serous carcinoma of the ovary or peritoneum
Showing posts with label low grade serous. Show all posts
Showing posts with label low grade serous. Show all posts
Thursday, May 17, 2012
paywalled - Gynecologic Oncology - Hormonal therapy for recurrent low-grade serous carcinoma of the ovary or peritoneum
ScienceDirect.com - Gynecologic Oncology - Hormonal therapy for recurrent low-grade serous carcinoma of the ovary or peritoneum
add your opinions
hormonal therapy
,
low grade serous
Sunday, April 01, 2012
AACR: Selumetinib Controlled Recurrent Low-grade Serous Ovarian Cancer
Selumetinib Controlled Recurrent Low-grade Serous Ovarian Cancer:
- Selumetinib controlled the disease in 81 percent of patients.
- Median progression-free survival was 11 months.
- Patients experienced minimal side effects.
The first line of defense against low-grade serous ovarian cancer is surgery, followed by cytotoxic chemotherapy. However, this is a slow-growing cancer and does not respond well to traditional chemotherapies, which target fast-growing cells.
Seeking a more rational treatment approach, Gynecologic Oncology Group (GOG) researchers led by John Farley, M.D., a professor at Creighton University School of Medicine at St. Joseph’s Hospital and Medical Center in Omaha, Neb., used selumetinib to target the MEK-1/2 protein kinase in the MAPK pathway, which is known to mutate in this form of cancer.
GOG researchers assigned 52 women to 100-mg doses of selumetinib orally twice daily in four-week cycles; 33 percent underwent 12 or more cycles. Prior to the study, 58 percent of patients had received three or more rounds of chemotherapy.
Selumetinib controlled the disease in 81 percent of patients. Specifically, eight patients had complete or partial responses to treatment, and 34 had stable disease. The median survival rate without cancer progression was 11 months, and 63 percent of patients had progression-free survival longer than six months. In addition, selumetinib was well tolerated, with three patients experiencing grade 4 adverse events.
“The results were striking,” said Farley. “Many of the patients in the study had received multiple rounds of chemotherapy and were running out of options. By using these tumors’ historical inherent molecular aberrations to select patients for a treatment that in theory could exploit these abnormalities, we took an important step toward individualized cancer therapies.”
In addition to studying the impact of selumetinib on this type of ovarian cancer, investigators were also interested in how patients with RAS/RAF mutations responded to the drug. The team analyzed the tumor DNA from 34 patients, 62 percent of whom had some form of RAS/RAF mutation. Ultimately, they found that RAS/RAF mutations had no impact on patient response.
The study was funded by the National Cancer Institute.
add your opinions
adverse events
,
low grade serous
,
selumetinib
,
side effects
Saturday, March 31, 2012
(Apr 2012) Commentary: Link between endometriosis and ovarian-cancer subtypes : The Lancet Oncology
Link between endometriosis and ovarian-cancer subtypes : The Lancet Oncology
"Previous large epidemiological studies have
attempted to identify benign gynaecological disorders that predispose to
the development of epithelial ovarian cancer. The only disorder that
has been repeatedly1—4 (although not universally5)
associated with this cancer is endometriosis. Results of some of these
studies have suggested a specific link with endometrioid and clear-cell
ovarian cancers, but until now none had the power to allow definitive
subgroup analysis based on a contemporary definition of histological
subtype.
In a study reported in the Lancet Oncology, Celeste Leigh Pearce and colleagues6
assessed self-reported endometriosis data from 13 pooled case—control
studies in the Ovarian Cancer Association Consortium (OCAC). They
confirm that a history of endometriosis is significantly associated with
an increased risk of clear-cell (odds ratio 3·05, 95% CI 2·43—3·84) and
endometrioid (2·04, CI 1·67—2·48) ovarian cancers, and for the first
time show an association with low-grade serous ovarian cancer (2·11,
1·39—3·20). No association was noted between endometriosis and
high-grade serous, mucinous, serous borderline, or mucinous borderline
ovarian cancers.
With more than 23 000
participants (7911 with a diagnosis of ovarian cancer), the main
strengths of this study are its statistical power and its robust
methods. Incidences of reported endometriosis differ substantially
between the pooled studies. Although clinicopathological and genetic
differences between the populations could reasonably be expected,
importantly there was no significant heterogeneity of the association
with histological subtype in the different studies.
The
main truly novel finding is an association between a history of
endometriosis and low-grade serous ovarian cancer. Perhaps surprisingly,
serous borderline tumours (from which invasive low-grade serous ovarian
cancers are believed to arise7)
are not also associated with a history of endometriosis.
add your opinions
ARID1A
,
borderline
,
braf
,
clear cell
,
endometrioid
,
endometriosis
,
ERBB2
,
KRAS
,
low grade serous
,
serous
,
varian cancer association consortium
Wednesday, March 07, 2012
abstract: Hormonal therapy for recurrent low-grade serous carcinoma of the ovary or peritoneum
Hormonal therapy for recurrent low-grade serous carcinoma of the ovary or peritoneum
Objective
To determine whether hormonal therapies have efficacy in patients with recurrent low-grade serous carcinoma of the ovary or peritoneum.
Methods
We searched departmental databases for patients with histologically-confirmed, evaluable, recurrent low-grade serous ovarian or peritoneal carcinoma who received hormonal therapy at our institution between 1989 and 2009. We retrospectively reviewed patients’ medical records for demographic, disease, hormonal therapy, and estrogen receptor and progesterone receptor expression data. We used the Response Evaluation Criteria in Solid Tumors version 1.1 to determine patients’ responses to hormonal therapy. Because patients could have received more than one evaluable hormonal therapy regimen, we chose to define the outcome metric as “patient-regimens.” Median time to disease progression (TTP) and overall survival (OS) were also calculated. Regression analysis was also performed.
Results
We identified 64 patients with recurrent low-grade serous carcinoma of the ovary or peritoneum. Patients’ median TTP and median OS were 7.4 and 78.2 months, respectively. Patients received 89 separate hormonal patient-regimens, which produced an overall response rate of 9% (6 complete responses and 2 partial responses). Sixty-one percent of the patient-regimens resulted in a 6-month progression-free survival duration of at least 6 months. Patient-regimens involving ER +/PR + disease produced a longer median TTP (8.9 months) than patient-regimens involving ER +/PR- disease did (6.2 months;p = 0.053). This difference approached but did not reach statistical significance.
Conclusions
Hormonal therapies have moderate anti-tumor activity in patients with recurrent low-grade serous carcinoma of the ovary or peritoneum. Further study to determine whether ER/PR expression status is a predictive biomarker for this rare cancer subtype is warranted.
Highlights
► Hormonal therapies have moderate anti-tumor activity in women with recurrent low-grade serous carcinoma of the ovary or peritoneum.► Further study to determine whether ER/PR expression status is a predictive biomarker for this rare cancer subtype is warranted.
► Low-grade serous carcinoma of the ovary or peritoneum is a unique entity.
add your opinions
hormone therapy
,
low grade serous
Monday, February 13, 2012
Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features.
Abstract
Malignant epithelial tumors (carcinomas) are the most common ovarian cancers and also the most lethal gynecological malignancies.
Based on histopathology and molecular genetic alterations, ovarian carcinomas are divided into five main types (high-grade serous (70%), endometrioid (10%), clear cell (10%), mucinous (3%), and low-grade serous carcinomas (5%)) that account for over 95% of cases.
These types are essentially distinct diseases, as indicated by differences in epidemiological and genetic risk factors, precursor lesions, patterns of spread, and molecular events during oncogenesis, response to chemotherapy, and prognosis. For a successful specific treatment, reproducible histopathological diagnosis of the tumor cell type is critical.
The five tumor types are morphologically diverse and resemble carcinomas of the uterus. Actually, recent investigations have demonstrated that a significant number of cancers, traditionally thought to be primary ovarian tumors (particularly serous, endometrioid, and clear cell carcinomas), originate in the fallopian tube and the endometrium and involve the ovary secondarily. This review summarizes recent advances in the molecular pathology which have greatly improved our understanding of the biology of ovarian carcinoma and are also relevant to patient management.
Friday, January 27, 2012
intereview with Dr David M. Gershenson: Clinical Challenges of Low-Grade (serous) Ovarian Cancer (includes comment on BRAF mutations, borderline tumors, age...)
Editor's Note:
About 10% of all serous ovarian carcinomas are low grade. Recent research indicates that these tumors differ in major ways from high-grade serous ovarian carcinomas. David M. Gershenson, MD, who holds the J. Taylor Wharton, MD, Distinguished Chair in Gynecologic Oncology at The University of Texas MD Anderson Cancer Center in Houston, Texas, discussed with Medscape current approaches to low-grade serous carcinoma of the ovary and peritoneum................................................................
Blogger's Note: a selected item below - read full article for more information:
Medscape: What is the next step for LGSC clinical research?
Dr. Gershenson: The major finding in the GOG 0239 study was a higher response with the MEK inhibitor than with conventional chemotherapy or hormonal therapy, so these drugs need to be studied further. They should also be tested in conjunction with drugs that block the PI3-kinase/Akt pathway. Dual pathway blockade may be required to produce a more robust response.
In the GOG 0239 trial, we saw a response rate of slightly over 15%, which is about 3-fold higher than with conventional chemotherapy and about 50% higher than with hormonal therapies in the recurrent setting. Unlike the situation with melanoma, there was no correlation with mutational status. That was something of a surprise and suggests that we don't understand what the impact of having a mutation is. I was certainly disappointed that there was not a correlation. We are looking at other markers in that pathway using data from that trial, and that analysis has not yet been completed..........
....Finally, the principal advance over the past decade is the recognition of LGSC as a distinct entity[9] -- very different from the typical high-grade ovarian cancers. Women with this subtype deserve separate clinical trials and treatment options.
add your opinions
GOG 0239 trial
,
low grade serous
Sunday, April 24, 2011
abstract: Calculator for ovarian carcinoma subtype prediction : Modern Pathology
Abstract:
With the emerging evidence that the five major ovarian carcinoma subtypes (high-grade serous, clear cell, endometrioid, mucinous, and low-grade serous) are distinct disease entities, management of ovarian carcinoma will become subtype specific in the future.
In an effort to improve diagnostic accuracy, we set out to determine if an immunohistochemical panel of molecular markers could reproduce consensus subtype assignment.
Immunohistochemical expression of 22 biomarkers were examined on tissue microarrays constructed from 322 archival ovarian carcinoma samples from the British Columbia Cancer Agency archives, for the period between 1984 and 2000, and an independent set of 242 cases of ovarian carcinoma from the Gynaecologic Tissue Bank at Vancouver General Hospital from 2001 to 2008. Nominal logistic regression was used to produce a subtype prediction model for each of these sets of cases. These models were then cross-validated against the other cohort, and then both models were further validated in an independent cohort of 81 ovarian carcinoma samples from five different centers.
Starting with data for 22 markers, full model fit, backwards, nominal logistic regression identified the same nine markers (CDKN2A, DKK1, HNF1B, MDM2, PGR, TFF3, TP53, VIM, WT1) as being most predictive of ovarian carcinoma subtype in both the archival and tumor bank cohorts. These models were able to predict subtype in the respective cohort in which they were developed with a high degree of sensitivity and specificity (κ statistics of 0.88±0.02 and 0.86±0.04, respectively).
When the models were cross-validated (ie using the model developed in one case series to predict subtype in the other series), the prediction equation's performances were reduced (κ statistics of 0.70±0.04 and 0.61±0.04, respectively) due to differences in frequency of expression of some biomarkers in the two case series. Both models were then validated on the independent series of 81 cases, with very good to excellent ability to predict subtype (κ=0.85±0.06 and 0.78±0.07, respectively).
A nine-marker immunohistochemical maker panel can be used to objectively support classification into one of the five major subtypes of ovarian carcinoma.
add your opinions
biomarkers
,
cancer subtypes
,
clear cell
,
endometrioid
,
high grade serous
,
low grade serous
,
mucinous
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