Monday, February 17, 2020

Genetic Links to Ovarian Cancer

I stumbled across this interesting and informative   website during a recent on-line search. Published by the National Institutes of Health (NIH)/Genetics Home Reference section, the article gives a basic overview of the origins, frequency, causes, inheritance patterns, diagnosis and treatment options etc. of ovarian cancer.

What makes this website unique are the sidebars associated with each section providing informational links. For example, one link connects to a new page explaining why some genetic conditions are found more often in particular ethnic groups. There were also over 20 additional links to further resources.

To find out more about this website, follow this link.


Monday, February 10, 2020

Endometriosis Appears to Have No Effect on Ovarian Cancer Outcomes, But More Research Needed, Study Says

This was a small study that examined the link between endometriosis and ovarian cancer. It appeared on the Clearity Foundation website.


Endometriosis does not seem to significantly affect ovarian cancer prognosis and survival in patients of reproductive age, a small study suggests.

However, more research is needed to identify factors associated with the progression of endometriosis to cancer and also to identify women who would benefit from more aggressive endometriosis treatment.
Ovarian cancer risk factors include a number of variables, such as age, weight, menstrual history, pregnancy history, smoking, inheritance of certain mutations, and benign gynecological conditions, including endometriosis.
Specific risk incidences vary depending on the type of cancer, but according to a study published in The Lancet, overall, endometriosis was estimated to increase ovarian cancer risk by nearly 50%.
However, it remains unclear whether there is a meaningful clinical difference between ovarian cancer in a person with endometriosis (endometriosis-associated ovarian carcinoma, EAOC) and the same type of cancer in a person without endometriosis (non-endometriosis-associated ovarian cancer, non-EAOC).
This is of particular interest in younger individuals, since age itself is independently associated with different ovarian cancer prognoses (younger age seems to be a prognostic factor for improved survival). Moreover, endometriosis is most common in people between 25 and 35 years old, according to the authors of the study.
The researchers analyzed medical records of people 40 years of age or younger who were treated for ovarian cancer at the Peking Union Medical College Hospital in China between 2006 and 2017.
Specifically, the researchers compared cases of EAOC, comprising either ovarian endometrioid carcinoma (OEC) or ovarian clear cell carcinoma (OCCC), with non-EAOC cases.
The studied group included 94 people with ovarian cancer — 40 with endometriosis (EAOC group) and 54 without (non-EAOC group). All of them were treated surgically; most also received chemotherapy.
In terms of outcomes, “a total of 77 (81.9%) patients were alive with no evidence of residual tumour at the time of the last visit, 4 (4.3%) patients were alive with the recorded disease, and 13 (13.8%) were dead of the recorded disease. There were no obvious differences between the two groups in terms of these variables,” the researchers wrote.
Further statistical analyses demonstrated that endometriosis was not significantly associated with an altered risk of disease progression or death. Another factor was, most notably, whether there was residual disease after initial treatment.
On the whole, there were “no differences in clinicopathological [disease-causing] or prognostic features,” between ovarian cancer in people with or without endometriosis, according to the researchers.
There was one exception: painful periods, or dysmenorrhea, which was reported by a much higher percentage of people with endometriosis than without (45% vs. 3.7%). But, the researchers said, this “is a typical symptom of patients with endometriosis,” and, as a result, most likely isn’t tied to the ovarian cancer.
This was a fairly small study of patients treated at a single center, so the results shouldn’t be generalized yet — there is still a need for further research to understand both endometriosis and ovarian cancer, and the intersection of both diseases.
“Endometriosis is not an independent prognostic predictor in patients with OCCC and OEC when age is confined to under 40 years. It is premature to consider ovarian cancers arising from endometriosis as a distinct entity,” the researchers concluded.
“This analysis also suggests that reproductive-aged women with early-stage OEC and OCCC should be offered conservative treatment,” they said. “Future research should focus on the identification of factors that are associated with the malignant transformation of endometriosis and how to identify women for whom more definitive endometriosis treatment would be appropriate to prevent ovarian cancer.”



Monday, February 3, 2020

Weekly Dose-Dense Chemo Not Recommended in First-Line Epithelial Ovarian Cancer Treatment

This article, by Matthew Fowler was orginally published published by the Clearity Foundation.

Weekly dose-dense paclitaxel as a frontline treatment for patients with epithelial ovarian cancer was not found to significantly improve progression-free survival (PFS) compared to the standard 3-weekly chemotherapy, according to results from the ICON8 study published in The Lancet.1

The results of the ICON8 trial show that it is feasible to deliver weekly dose-dense paclitaxel in combination with either 3-weekly or weekly carboplatin in the first-line treatment of high-risk ovarian cancer,” Andrew Clamp, PhD, of The Christie NHS Foundation Trust, and colleagues wrote. “However, neither of these regimens is associated with an improvement in survival outcomes compared with standard 3-weekly carboplatin–paclitaxel treatment in the predominantly European population treated on this trial.”
The phase III ICON8 trial randomly assigned predominantly European women with newly diagnosed International Federation of Gynecology and Obstetrics stage IC–IV epithelial ovarian cancer to 3 groups.
1,566 women from June 2011 to November 2014 were recruited for treatment as a part of the ICON8 study. In this 3 arm trial, patients in group 1 received carboplatin AUC5 or AUC6 and 175 mg/m2paclitaxel once every 3 weeks; patients in group 2 received carboplatin as in group 1 and dose-fractionated 80 mg/m2paclitaxel weekly; and patients in group 3 received carboplatin AUC2 and 80 mg/m2paclitaxel weekly.
Primary endpoints for the study were PFS and overall survival (OS). Both groups 2 and 3 were individually compared with group 1 (control group) to determine primary endpoint results. Secondary endpoints included safety, quality of life, and health economics.
The median PFS was 17.7 months for the control group (group 1), 20.8 months in group 2, and 21.0 months in group 3.
After a 9-month cross-analysis of the results, the study determined there was no significant difference between the groups with regards to quality of life. As for toxic effects, both group 2 and group 3 treatments were associated with increased instances of grade 3 or higher toxic effects, but these effects were deemed “uncomplicated.”
“Although most patients were able to complete 6 chemotherapy cycles, both weekly treatments were associated with more treatment modifications and a higher incidence of grade 3 or higher toxic effects,” stated in a press issued by the European Society for Medical Oncology (ESMO). “Although grade 3 or 4 toxic effects increased with weekly treatment, these effects were predominantly uncomplicated.”2
The population included both patients who underwent primary cytoreductive surgery (IPS) and those who chose delayed primary cytoreductive surgery (DPS) options. The results from each of these populations also stood as a secondary point of intrigue for the researchers. No significant relationship between surgical decision and treatment schedule was detected.
The ICON8 study was a large, international process including a variety of different patient variables, including demographic, surgery selection and treatment schedule. The study also yielded an 85% chemotherapy completion rate, allowing for valuable results to be drawn from the process. Even more, although the results did not yield a positive development for European women, the weekly-dose treatment can still be an option for Japanese women with epithelial ovarian cancer, who previously demonstrated a superior benefit to the regimen.2
“Weekly dose-dense paclitaxel treatment could still be considered as a first-line treatment option for Japanese women with epithelial ovarian cancer,” said in an ESMO press release. “But the weekly dose-dense paclitaxel should not be recommended as a component of first-line epithelial ovarian cancer treatment for women of non-Japanese ethnic origin.”
Two further studies have been done analyzing weekly dose-dense chemotherapy treatment within the lifetime of the ICON8 study, but the researchers recommend even more investigation into this treatment among different ethnic groups.
This article was published by Cancer Network.

Monday, January 27, 2020

Niraparib in Patients With Newly Diagnosed Ovarian Cancer

This article appeared in the New England Journal of Medicine (NEJM). The conclusion showed that women with newly diagnosed OC who were not platinum resistant had a longer progression free survival - regardless of their BRCA status - than those on placebo.

Here's the abstract to the study:

Abstract

BACKGROUND

Niraparib, an inhibitor of poly(adenosine diphosphate [ADP]–ribose) polymerase (PARP), has been associated with significantly increased progression-free survival among patients with recurrent ovarian cancer after platinum-based chemotherapy, regardless of the presence or absence of BRCA mutations. The efficacy of niraparib in patients with newly diagnosed advanced ovarian cancer after a response to first-line platinum-based chemotherapy is unknown.

METHODS

In this randomized, double-blind, phase 3 trial, we randomly assigned patients with newly diagnosed advanced ovarian cancer in a 2:1 ratio to receive niraparib or placebo once daily after a response to platinum-based chemotherapy. The primary end point was progression-free survival in patients who had tumors with homologous-recombination deficiency and in those in the overall population, as determined on hierarchical testing. A prespecified interim analysis for overall survival was conducted at the time of the primary analysis of progression-free survival.

RESULTS

Of the 733 patients who underwent randomization, 373 (50.9%) had tumors with homologous-recombination deficiency. Among the patients in this category, the median progression-free survival was significantly longer in the niraparib group than in the placebo group (21.9 months vs. 10.4 months; hazard ratio for disease progression or death, 0.43; 95% confidence interval [CI], 0.31 to 0.59; P<0.001). In the overall population, the corresponding progression-free survival was 13.8 months and 8.2 months (hazard ratio, 0.62; 95% CI, 0.50 to 0.76; P<0.001). At the 24-month interim analysis, the rate of overall survival was 84% in the niraparib group and 77% in the placebo group (hazard ratio, 0.70; 95% CI, 0.44 to 1.11). The most common adverse events of grade 3 or higher were anemia (in 31.0% of the patients), thrombocytopenia (in 28.7%), and neutropenia (in 12.8%). No treatment-related deaths occurred.

CONCLUSIONS

Among patients with newly diagnosed advanced ovarian cancer who had a response to platinum-based chemotherapy, those who received niraparib had significantly longer progression-free survival than those who received placebo, regardless of the presence or absence of homologous-recombination deficiency. (Funded by GlaxoSmithKline; PRIMA/ENGOT-OV26/GOG-3012 ClinicalTrials.gov number, NCT02655016. opens in new tab.)

Monday, January 20, 2020

Where Does Ovarian Cancer Originate?

It used to be thought that the ovaries were the origin of high grade serous ovarian cancer - certainly the name of the cancer suggests its origins. However research at multiple health centers points to another source: the fallopian tubes.

The consortium of centers included Johns Hopkins University, Toronto University Health Network, Yale University and Memorial Sloan-Kettering Cancer Center. Using molecular profiling, researchers were able to show that the cellular origin of the cancer was most closely aligned to the fallopian tube region rather than the ovaries. This is significant because in high-risk women, currently the ovaries and the fallopian tubes are generally removed. The ability to preserve the ovaries could reduce the risk of heart disease, osteoporosis and other diseases associated with ovarian resection.

To read more about this study, follow this link.  



Monday, January 13, 2020

SCIENTISTS DEVELOP PROMISING DRUG FOR TREATING OVARIAN AND PANCREATIC CANCERS

As we know, ovarian and pancreatic cancer are very difficult to treat because by the time they are diagnosed, they are often late stage.

Houston Methodist and MD Anderson have filed a joint patent for a new monoclonal antibody. (Monoclonal antibodies are cloned from a single parent cell and can mimic a variety of immune functions in cancer treatment.)

MFAP5, a protein secreted in high levels in both these cancers, is a marker of poorer survival rates. Researchers have developed a monoclonal antibody that blocks MFAP5 found in the areas surrounding the tumor cells that feed and support the tumor. Blocking MFAP5 effectively starves the tumor since MFAP5 is associated with sustaining the tumor with nutrients. Without this, these cells are more sensitive to chemo. Phase 1 clinical trials will hopefully start in 2020.

You can read more about this by following this link

Monday, January 6, 2020

OUT OF MANY OVARIAN PRECANCEROUS LESIONS, ONE BECOMES CANCER

Turns out there is not just one smoking gun in pre-cancerous lesions that lead to ovarian cancer. Instead, researchers at Johns Hopkins discovered that some women can have multiple pre-cancerous lesions which are not driven by one specific set of mutations. Many of these pre-cancerous lesions simply remain dormant. Additionally, it can take decades before some of these lesions develop into OC.

Now researchers need to determine which of these precursors will go on to become ovarian cancers as well as how to detect them.

This article first appeared on the Johns Hopkins Institute for Clinical and Translational Research website.

Some deadly ovarian cancers arise from lesions genetically unrelated to each other.
In a novel study of cancer genetics using fallopian tube tissue from 15 women, researchers at the Johns Hopkins Kimmel Cancer Center say they have found evidence that the most common and lethal type of ovarian cancer arises not from a uniform group of precancerous lesions, but from individual growths found in groups genetically unrelated to each other.
If confirmed in further studies, the discovery, described in the May issue of the Journal of Pathology, would go a long way towards upending a longstanding cancer dogma dictating that cancer steadily progresses from any and all precancerous lesions, and could lead to new ways to fight this deadly disease.
“We’re finding that it’s not a straight line progress from precancerous lesions to cancer in these tumors,” says Ren-Chin Wu, Ph.D., first author and associate professor at Chang Gung University School of Medicine in Taiwan  “If we can find a way to eradicate just the ones that progress, and distinguish them from those that maintain dormancy forever, we likely can make treatments more effective and save more women’s lives,” he adds.Up to 70 percent of all ovarian cancers are so-called high-grade serous carcinomas (HGSCs) and account for the vast majority of the 14,000 women who die of ovarian cancer each year in the U.S., explains study leader Tian-Li Wang, Ph.D., director of the Molecular Genetics Laboratory of Female Reproductive Cancer and professor of pathology, oncology, and gynecology and obstetrics at the Johns Hopkins University School of Medicine. “This cancer is incredibly hard to beat because it’s usually diagnosed at a late stage since earlier stages have few to no symptoms,” says Wang.
Recent studies, Wang notes, suggest that these ovarian cancers arise from precancerous lesions in the fallopian tubes, a pair of organs that carry eggs from the ovaries to the uterus. But how this progression proceeds from precancerous lesions to active cancer has been unclear.
To investigate this biological path, Wang and her colleagues, including first author Wu, studied fallopian tube and ovarian tissue from 15 women seen at the Johns Hopkins Hospital.
Eleven of these women had no evidence of cancer when these organs were removed prophylactically to reduce their cancer risk. The other four already were diagnosed with HGSCs.
Using high-powered microscopes, the researchers first identified a variety of different precancerous lesions clustered in three groups according to pathological diagnostic markers on the women’s fallopian tubes. They then removed cells from these lesions using a technique called laser capture microdissection to determine how fast the cells in each of the lesions were dividing, and to enable analysis of their genetic mutations.
The researchers say they found these precancerous lesions were in a variety of stages of activity. Some were dormant and not actively proliferating. Others were proliferating but weren’t yet cancer.
Overall, their genetic analyses on 24 lesions in 11 women identified mutations in 12 different cancer-related genes. Surprisingly, they say, one cancer-free woman had multiple precursor tubal lesions and each appeared to be driven by different sets of mutations, suggesting that they weren’t derived from a common primary lesion and had each arisen independently.
In three of the four women with active ovarian cancer, the researchers were able to link their tumors genetically with a primary precursor lesion on their fallopian tubes. However, for one of the women, the researchers couldn’t find a genetic link with co-existing precancerous lesions—reinforcing the idea that while many precancerous lesions arise in women at risk for ovarian cancer, only some progress to active cancers.
Further experiments that modeled mutation progression in these tumors suggest that it may take decades for tumors to progress from precancerous lesions to HGSCs, says co-lead author Cristian Tomasetti, Ph.D., associate professor of oncology. This potentially offers a large window of time to intervene before cancers become advanced and difficult to treat, but he says researchers will first need to find ways to detect cancer precursors that are dangerous from those unlikely to cause any harm.”
“Unlike prior studies that analyzed precursors and cancers from the same patients, this study includes many precursor lesions without cancer present, and provides a unique molecular landscape of ovarian cancer precursors in place before ovarian cancer actually develops,” says Ie-Ming Shih, M.D., Ph.D., study co-author, Richard W. TeLinde Distinguished Professor, Department of Gynecology and Obstetrics and co-director of the Johns Hopkins Kimmel Cancer Center Women’s Malignancies Program.
Other Johns Hopkins researchers who participated in this study include Shiou-Fu Lin, Ming Zhang, Tiffany Chu, Robert J. Kurman, Russell Vang and Kenneth Kinzler.
This study was supported by funding from the US Department of Defense CDMRP (grant number W81XWH-11-2-0230); the National Institutes of Health/National Cancer Institute (grant numbers UO1CA200469, RO1CA215483, P50CA228991, P30CA006973); the Honorable Tina Brozman Foundation, Ovarian Cancer Research Fund Alliance, Roseman Foundation; Teal Award, and Gray Foundation; the John Templeton Foundation; the Richard W. TeLinde Endowment from the Johns Hopkins University.