Ovarian Cancer: Screening May Cut Deaths By A Fifth

Doctors say there is now “encouraging” evidence that an annual blood test may cut ovarian cancer deaths by a fifth.

Ovarian tumours are often deadly as they are caught too late.

A 14-year study on 200,000 women, published in the Lancet, has been welcomed as a potentially landmark moment in cancer screening.

But the researchers and independent experts say it is still too soon to call for mass screening because of concerns about the analysis.

Ovarian cancer is difficult to pick up as symptoms, including abdominal pain, persistent bloating and difficulty eating, are common in other conditions.

Blood Measure

The UK Collaborative Trial of Ovarian Cancer Screening is one of the biggest clinical trials ever conducted and is supposed to give the definitive verdict on screening.

It monitored levels of a chemical called CA125 in women’s blood.

Doctors tracked changes in the levels of CA125, which is produced by ovarian tissue, over time and if levels became elevated then the women were sent for further tests and ultimately surgery.

The results are now in, but the interpretation is a bit messy and the researchers admit it is “controversial”.

Their initial statistical analysis of the data showed no benefit to screening. But there was a benefit when they removed the data from any women who may have already started to develop ovarian tumours.

The researchers then performed a more forgiving statistical analysis, which also showed a benefit.

Ovarian cancer

Trial leader Prof Usha Menon, from UCL, told the BBC News website: “Is there clear evidence? I would say no.

“We don’t have clear evidence to go ahead with screening, but what we have are really encouraging estimates of around a 20% reduction, which we need to confirm.”

Any benefit to screening seems to be delayed – kicking in towards the end of the trial.

The researchers are continuing to follow the patients for what is expected to be another three years to confirm whether there is a benefit.

Kevin McConway, a professor of applied statistics at the Open University, said: “Doing these extra analyses can be seen as an appropriate response to how the data turned out to look, which in some respects weren’t as they originally expected.

“But equally it is also the case that the more analyses done, the more likely it is that one of the results will come out as positive.

“The results are promising, but perhaps not all that promising.”

To Screen Or Not To Screen?

There is also the risk that screening can do harm and the test led to some women having unnecessary surgery to remove benign growths.

Dr Adam Shaw, the clinical lead for cancer genetics at Guy’s & St Thomas’ NHS Foundation Trust, said the findings were “very encouraging” but there was still more work to do.

“Nonetheless, this study is a landmark step in devising effective screening for ovarian cancer, which is often portrayed as the silent killer.”

Dr Fiona Reddington, from Cancer Research UK, said: “It’s uncertain whether or not screening can reduce ovarian cancer deaths overall.

“While this is an important step in ovarian cancer research, we would not recommend a national screening programme at this point.”

The UK’s National Screening Committee, which decides what diseases should be screened for, says it will have to make a “scientifically sound decision” and will review the findings.

To read this entire article about ovarian cancer screening on BBC, click here.

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Early Detection of Ovarian Cancer May Become Possible

A new version of a screening test for ovarian cancer may reduce deaths from the disease, but it needs more study to determine whether the benefits hold up, researchers reported on Thursday.

The findings come from a 14-year study of more than 200,000 women in Britain, published in The Lancet.

“We need to follow up to confirm that this is absolutely significant throughout,” said Dr. Usha Menon, an author of the Lancet article and head of the gynecological cancer center at University College London. She said, “This is almost there, but not yet.”

Her reason for caution was that the study passed only two of three tests of statistical significance, which means that the apparent benefits of screening might have been due to chance. She said a few more years of monitoring the participants would resolve that question.

Deborah Denehy received chemotherapy directly to her abdomen to treat ovarian cancer, a treatment that remains underused in the United States.
No existing method of ovarian cancer screening helps reduce deaths, Dr. Virginia A. Moyer said.Ovarian Cancer Screening Has No Benefit, Panel SaysSEPT. 10, 2012

The study results have been long awaited because ovarian cancer has a poor prognosis. The disease has no symptoms in its early stages and can progress rapidly, so most cases are advanced by the time they are found. Only about 45 percent of ovarian cancer patients are still alive five years after a diagnosis.

This year, 21,290 new cases and 14,180 deaths from ovarian cancer are expected in the United States, according to the American Cancer Society.

Past efforts to find a screening method have focused on two tests: ultrasound examinations of the ovaries, and a blood test to measure CA125, a “tumor marker” sometimes linked to early-stage disease. But in previous studies, those tests did not work: They did not lower the death rate and they produced too many false-positive results that led healthy women to have unnecessary surgery.

The Lancet study also used CA125, but in a different way. Instead of declaring a certain level abnormal, the researchers developed a mathematical formula that took into account a woman’s age and the degree of change in CA125 over time, and calculated a risk score.

Angelina Jolie PittOp-Ed Contributor: Angelina Jolie Pitt: Diary of a SurgeryMARCH 24, 2015
Experts not associated with the Lancet study agreed that the test was not ready for routine use, and they varied in their optimism about it.

“It is good news because ovarian cancer is a serious problem,” said Robert Smith, the vice president for cancer screening at the American Cancer Society. “The incidence is not high, but it has a high mortality rate and we’ve not been able to offer women much with respect to early detection. This has the potential to change that.”

Dr. Tanveer P. Mir, chairwoman of the board of regents of the American College of Physicians, said she thought the test had great promise and expected that the college’s special task force on screening tests would evaluate the study and consider endorsing it.

Dr. Edward E. Partridge, the director of the comprehensive cancer center at the University of Alabama at Birmingham, said, “It gives us a glimmer of hope, but boy, it’s a long way from being implemented as a public health policy.”

Dr. Karen H. Lu, the chairwoman of the department of gynecologic oncology and reproductive medicine at the University of Texas MD Anderson Cancer Center, called the Lancet research “a solid triple, but not a home run.”

“It’s a lot of screening for a small amount of benefit,” said Dr. Saundra S. Buys, a professor of medicine and medical director of the high-risk breast cancer clinic at the University of Utah’s Huntsman Cancer Institute. She called the study “an amazing accomplishment,” but said the real problem is that ovarian cancer is not amenable to screening because of its lack of symptoms and aggressive growth.

An advocacy group, the Ovarian Cancer National Alliance, issued a statement that called the study promising, but said much more data analysis was needed to determine whether the test would be useful.

The study was paid for by the British government and the Eve Appeal, a charitable group in Britain. Dr. Menon and several other authors have financial interests in a British company, Abcodia, that will be marketing the new version of the CA125 test.

From 2001 to 2005, the study enrolled 202,638 women ages 50 to 74 who had an average risk of ovarian cancer. The women were picked at random to join one of three groups.

About half were assigned to a control group that received no screening.

Some 50,000 others were given CA125 tests, interpreted with the new formula, known as the Risk of Ovarian Cancer Algorithm. If they had abnormal findings, other tests would be done, possibly leading to surgery to remove the ovaries.

Another 50,000 had just ultrasound scans of the ovaries once a year, with more tests, if needed, to follow up on suspicious results.

Annual screenings were done until December 2011, and the women were tracked through December 2014. The median follow-up was 11.1 years. In the unscreened group, there were 630 ovarian cancers, with 347 deaths from the disease; in the CA125 group, 338 cases and 148 deaths; in the ultrasound group, 314 cases and 154 deaths.

The first analysis found decreased deaths in both the CA125 and ultrasound groups, but the differences were not statistically significant. A second analysis, excluding women found to have ovarian cancer shortly after they entered the study, found 20 percent fewer deaths in the women screened with the CA125 algorithm. Further statistical tests showed that the differences in death rates did not emerge until the seventh year of the study — probably because once a woman enters, it takes time for the disease to develop, and then more time for her to die, Dr. Menon said.

She said the findings were the first evidence from a randomized, controlled trial that screening can reduce ovarian cancer deaths.

To save one life, the researchers calculated, 641 women had to be screened annually for 14 years. For each ovarian cancer detected, 2.2 women had surgery that turned out to be unnecessary — a rate that researchers consider low. The rate of major complications from those operations was 3.1 percent.

An important strength of the method, Dr. Lu said, “is that they don’t do many unnecessary surgeries.” But she emphasized that the screening “is not here now.”

To read this article by The New York Times, click here.

Fallopian Tube Organoids Promise Better Understanding Of Ovarian Cancer And Infertility

A new way of growing Fallopian tube cells in culture is expected to give a boost to our understanding and prevention of female genital diseases, such as infertility, inflammatory disease, and ovarian cancer.

A new way of growing fallopian tube cells in culture is expected to give a boost to our understanding and prevention of female gynecological diseases, such as infertility, inflammatory disease, and ovarian cancer. The tubes, which connect the ovaries with the uterus, are the site of fertilization but they are now also believed to be the site from which high-grade serous ovarian carcinoma originates – the deadliest form of gynecological cancer. From the open end of the tube early cancer cells appear to spread not only to the ovaries, but also to other organs in contact with the abdominal cavity. Ascending gynecological infections, on the other hand, can lead to inflammation, scarring and closure of the fallopian tubes, which frequently leads to infertility or ectopic pregnancies. Both ovarian cancer and pelvic inflammatory disease often start silently and are not diagnosed until the late stages, as the inner lining of the tube, the fallopian epithelium, is inaccessible to direct clinical examination.

Until now, research into the origins and etiology of the diseases has also been restricted because fallopian epithelial cells cannot readily be grown in the laboratory. Together with researchers at the gynecology centers of the Charitè University Hospital, a team led by Thomas F. Meyer at the Max Planck Institute for Infection Biology in Berlin has now harnessed a new method of growing human epithelial cells as hollow spheres, so called ‘organoids’, in order to culture cells from clinical fallopian tube samples. By adapting the culture conditions to the specific needs of the tissue, they were able to keep the adult stem cells of the fallopian tube alive, so that they continue to proliferate and produce the cells typical of this tissue.

Importantly, the fallopian organoids have the same composition and structure as the epithelial lining of the tube. ‘We have learned not only how to achieve conditions that allow cells to develop all features present in the human body, but also how to control their specialization into the different cell types found in the fallopian tubes’ says Mirjana Kessler, the first author of a paper that just appeared in Nature Communications. ‘The fallopian tube represents a crucial organ for female health: it is accessible to pathogenic microbes such as Chlamydia and at the same time provides a conduit into the abdominal cavity. It is the site of origin of several clinically important diseases for women, such as ovarian cancer, pelvic inflammatory disease and infertility.’

The new model should now enable scientists to investigate in detail different aspects of fallopian tube functions, such as its role in reproduction, impact of infections and the basic mechanisms behind serous ovarian carcinoma development offering numerous avenues of approach towards the development of much needed therapies and novel diagnostic tools.

To read this entire research article on EurekAlert!, click here.

Doing Good Really Is Good for You

If you’ve ever served Thanksgiving dinner at a homeless shelter, rung the bell for the Salvation Army, or written a check to a favorite charity, you probably recall the calm glow of satisfaction social scientists call the “helper’s high.” But do such acts of generosity have lasting physical benefits?

Yes, says Stephen G. Post, PhD, author of The Hidden Gifts of Helping. Recent studies show people who volunteer regularly have healthier hearts, less ongoing pain, and bolstered immune systems. They battle addiction better and are less likely to get dementia with age. They also live longer.

“The science is exploding,” Post says. “We have begun to discover that there is something going on, physiologically, in this process of helping others that makes people not only feel happier but also report greater health.”

As far back as 1988, an analysis of 1,700 female volunteers found that 68% said they felt a sense of calm after volunteering, akin to what they got from exercise. Decades later, studies used MRI image scans to track brain activity to explain why. One study of 19 people found that merely cutting a check to charity lights up the mesolimbic reward system (the same brain region that fires when we eat, have sex, or receive money), igniting a flood of feel-good chemicals in the body. When that generosity is practiced face-to-face, levels of oxytocin (the calming hormone released when a mother nurses her infant) and pain-killing endorphins also rise, Post says.

Meanwhile, as we shift our minds away from our own troubles to focus on others’ needs, levels of stress hormones like cortisol fall. One 2013 study of 1,654 older adults found that those who volunteered at least 200 hours per year were 40% less likely to get high blood pressure than non-volunteers.

An evolutionary reason may explain why our reward centers light up when we help someone else. Working in a team, Post and others say, could very well have helped us survive as a species. Some even suggest women’s innate tendency to “tend and befriend” rather than fight or fly in times of crisis could, by buffering stress hormones, partially account for why women live longer than men.

Volunteering may help you live longer and better, research shows.

Feeling Good

Post says these are the best ways to get the most out of volunteering:

Help others get through something you’ve gone through. Studies show recovering alcoholics are twice as likely to stay sober when they help other recovering alcoholics, and chronic pain sufferers see their pain lessen when they help someone with a similar condition.

Do what you’re good at. When volunteers feel like they’re just in the way, the experience can backfire and boost their stress. Choose a volunteer opportunity where you can make a real contribution.

Mean it. Those who contribute to organizations they’re passionate about see stronger physical responses. “Motivation matters,” Post says. “When people are genuinely altruistic in their actions, they have a better response.”

To read this entire article on WebMD, click here.

Older Women Received Less Treatment For Ovarian Cancer

Women older than 70 received less treatment for ovarian cancer than did their younger counterparts, according to the results of a single-center French study. In fact, these women received less treatment regardless of stage or grade of their disease.

“The cancer characteristics being equal, elderly women had less chance of receiving standard therapy, ie, the recommended treatment by current guidelines,” Elisabeth Fourcadier, of Cancer Registry of Hérault Departement of France, ICM, and colleagues wrote in BMC Cancer. “Elderly patients in whom guidelines-recommended treatment was not applied had poorer likelihood of survival as compared to elderly patients who received guidelines-recommended therapy, and as compared to younger women.”

According to the study, older women are more likely to have a delayed diagnosis of ovarian cancer and are more likely to be diagnosed at an advanced stage. Surgery with or without chemotherapy is the standard treatment for ovarian cancer and previous studies have shown that this aggressive treatment may be less likely to be used in older populations.

In this study, Fourcadier and colleagues looked at 1,151 women diagnosed with invasive ovarian cancer between 1997 and 2011; about 40% of women were aged 70 or older. They analyzed their age, cancer characteristics, and treatment.

Older women were more likely to be diagnosed at a more advanced stage compared with younger women (P < .0001). In addition, older women were less likely to undergo or have unknown histology testing results (P < .001).

Overall, their analysis revealed that older women with ovarian cancer received less treatment compared with younger women regardless of the treatment type. Whereas 60.9% of older women underwent surgery, 89.6% of younger women did (P < .001). Similarly, only 57.4% of older women underwent chemotherapy compared with 76.4% of younger women (P < .001). Multivariate adjustments showed that older women were 3.6 times less likely to have surgery and three times less likely to be assigned chemotherapy compared with younger women. Similar disparities were discovered according to cancer stage.

The researchers conducted a multivariate regression adjusted analysis for cancer characteristics, treatment location, and period of diagnosis and found a gradient effect between treatment and age linked to the introduction of chemotherapy and its association with surgery:

• Odds ratio (OR) for surgery in women > 70 vs ≤ 70 years, 0.46;

• OR for chemotherapy > 70 vs ≤ 70 years, 0.29; and

• OR for surgery plus chemotherapy > 70 vs ≤ 70 years, 0.13.

“Furthermore, we showed that standard guidelines-recommended therapy was less frequently applied in the elderly, and hence, elderly patients were 50% less like to receive standard therapy than younger patients,” the researchers wrote. “Elderly patients have improved likelihood of survival when recommended treatment is applied. Further research, however, is warranted to investigate whether the independent effect of age persists in the presence of comorbidity.”

To read the entire study or to learn more, visit Cancer Network by clicking here.

Obesity Contributes To Metastasis In Ovarian Cancer Patients

Ovarian cancer is a deadly disease, one that’s hard to detect until it has progressed significantly. More than 75 percent of women diagnosed with ovarian cancer have metastasis at the time of diagnosis, resulting in a low five-year survival rate of less than 30 percent.

A large number of studies have shown that an increased body mass index (BMI) is associated with a greater risk for ovarian cancer with worse overall survival. More than 35 percent of women in the United States are obese, putting them at increased risk for the cancer.

However, the influence of obesity on ovarian cancer metastasis had not been evaluated. Researchers from the University of Notre Dame and its affiliated Harper Cancer Research Institute (HCRI) unveil important new insights into the relationship between ovarian cancer and obesity.

M. Sharon Stack, Ann F. Dunne and Elizabeth Riley Director of the HCRI and professor of chemistry and biochemistry, notes that ovarian cancer is the leading cause of death from gynecologic malignancy in the U.S. The researchers set out to determine whether obesity contributes to ovarian cancer metastatic success. In other words, are tumor cells better able to successfully metastasize when the “host” is obese versus lean?

“Ovarian cancers metastasize through a distinct mechanism that results in large numbers of lesions anchored throughout the abdominal cavity, making surgery challenging,” Stack said

Stack and Harper researcher Yueying Liu led a team of researchers that used an integrative approach combining three-dimensional cell culture models, tissue explants and mouse models to evaluate tumor cell adhesion to the cells that line the abdominal cavity, called “mesothelial cells.”

“In 3-D tissue culture models, we found that lipid-loading the mesothelial cells, or growing them in the presence of components that make up fat, increased the ability of tumor cells to bind to them,” Stack said. “As tumor cell-mesothelial cell binding is a key step in ovarian cancer metastasis, this prompted us to study this further in mouse models. We used a ‘diet-induced obesity’ (DIO) protocol in which mice were fed a high fat diet, which was 40 percent fat, relative to mice fed control chow. When mice were significantly different in weight, they were injected with fluorescent ovarian cancer cells, and we monitored metastatic seeding in the abdominal cavity by in vivo imaging.”

Individual organs were removed from the mice and imaged to quantify tumor burden in each organ. Researchers also used another mouse model of obesity, termed the ob/ob mouse, which harbored a mutation that caused it to become highly obese.

“In all of these models, we found that obesity enhances ovarian cancer metastatic success,” Stack said.

The researchers hope that further research in this direction may provide new targets for dietary and therapeutic interventions to slow or inhibit metastatic dissemination and thereby impact the long-term survival of women with ovarian cancer. However, Stack pointed out that they are just at the beginning of understanding this complex disease.

“The peritoneal cavity is a complicated microenvironment, containing tumor cells, immune cells, fluid and many host organs,” she said. “Our ongoing efforts are aimed at understanding the mechanism by which obesity impacts metastatic success. For example, we have found that tumors growing in obese host mice turn on lipid synthesis and lipid transport, suggesting that they are better able to acquire and utilize nutrients from fat. The blood supply to the tumors is also impacted, as is the presence of specific immune cells. There is still a lot of work needed to figure out where we can intervene in this process.”

The study was supported by grants from the National Cancer Institute and the Leo and Ann Albert Charitable Trust and by training fellowships from the National Cancer Institute and the National Science Foundation. Stack also noted that the interdisciplinary nature of the research.

“In addition to the cell-based research, we analyzed hundreds of fluorescent images and many hundreds of slides to collect the data to support our conclusions,” she said. “We had phenomenal interactions with the Harper Tissue Biorepository and the Notre Dame Integrated Imaging Facility. You can see the team effort by looking at the author listing: This paper has 22 authors. Seven of them are current or former Notre Dame undergrads, and four are current or former ND grad students.”

The study appears in the journal Cancer Research.

To read this research article in its entirety on Science Daily, click here.

 

Study Links Oral Contraceptive Use to Better Ovarian Cancer Outcomes

Ovarian cancer may progress more slowly in women who once used oral contraceptives (OCs) according to a retrospective study of patients treated at the Mayo Clinic in Rochester, MN.1

Study Links Oral Contraceptive Use to Better Ovarian Cancer Outcomes

In a video discussing the findings, lead author Aminah Jatoi, MD, an oncologist with the Mayo Clinic in Rochester MN, explained that whereas previous studies have found OC users were less likely to develop ovarian cancer, she and her colleagues “looked at other factors, specifically the prognosis of people who develop ovarian cancer…Interestingly, we found that those people who had been on OCs actually did better.”

The researchers recruited 1398 women aged 20 years or older who were treated at the Mayo Clinic between 2000 through 2013 for invasive primary epithelial ovarian cancer, fallopian tube cancer, or peritoneal cancer.

The women completed a self-administered questionnaire about their OC use, menstrual history, number of live births, and other hormone-related factors. Using electronic medical records, investigators compiled data on each woman’s cancer diagnosis and histology, surgical and medical treatments, smoking history, and family history of breast or ovarian cancer.

According to the questionnaires, 827 women had used OCs, and the median duration of use was 60 months. Younger women were more likely to report OC use.

Multivariate analyses showed significantly longer progression-free survival for women who had a history of OC use relative to women who had never used OCs (hazard ratio [HR], 0.78; 95% CI, 0.64 – 0.96; P = .02) but showed no significant difference in overall survival between the cohorts.

Univariate analyses suggested a significant advantage for OC users vs never-users in progression-free survival (HR, 0.71; 95% CI, 0.61 – 0.83; P < .0001) and overall survival (HR, 0.73; 95% CI, 0.62 – 0.86;P = .0002), but the overall survival benefit was no longer statistically significant once the researchers adjusted for the women’s age at diagnosis.

The authors did not include data on the type of OC, the timing of OC use relative to the ovarian cancer diagnosis, or the cause of death, which they acknowledged were limitations of the study. In Dr Jatoi’s video discussion, she said the findings were interesting, however, and merited further investigation.

She emphasized the need for other centers to confirm her group’s findings and for studies to determine how OCs might influence the course of ovarian cancer that is diagnosed several years after use. “Is it some change that occurs in the cancer itself as a result of changes in the microenvironment that lead to better outcomes when patients develop this disease?” Dr Jatoi asked.

The study authors offered a few hypotheses for the benefits of OCs on ovarian cancer survival. For example, suppressing ovulation might reduce monthly trauma to the ovary that stimulates epithelial cancer cells to replicate and acquire additional DNA mutations associated with more aggressive cancer.

Another theory is that the hormones used in the contraceptive provoke changes in the extracellular matrix that have long-term effects on the malignant potential of ovarian cancer and its vulnerability to systemic treatments. Dr Jatoi said the answer to these questions could have therapeutic potential. “We might be able to find out ways to intervene once patients have the tumor that result in their…doing better during that period after developing cancer.”

To read this study in full on Cancer Therapy Advisor, click here.