A Peek Into Big Data and Ovarian Cancer

By: Annette McElhiney

A Peek Into Big Data and Ovarian CancerOn July 29, 2017, I celebrated 9 years since my IIIC ovarian cancer debulking surgery.  Because I’ve been so fortunate to be in remission, I spend hours each day researching, writing, and corresponding with other ovarian cancer survivors as well as any cancer survivors.

I follow all the postings on ovarian cancer that I can find. On a recent morning, I discovered this fascinating video on ways of using Big Data in Ovarian Cancer. After reading this brief introduction, I invite you to watch the video, ‘A Story of Big Data, Cancer, and Collaboration.

In 2011, a group of researchers compiled  The Cancer Genome Cancer Atlas or TCGA which addresses specifically several other diseases in addition to ovarian cancer.

As Wikipedia states, “The Cancer Genome Atlas (TCGA) is a project, begun in 2005, to catalogue genetic mutations responsible for cancer, using genome sequencing and bioinformatics. TCGA applies high-throughput genome analysis techniques to improve our ability to diagnose, treat, and prevent cancer through a better understanding of the genetic basis of this disease.”

“TCGA is supervised by the National Cancer Institute’s Center for Cancer Genomics and the National Human Genome Research Institute funded by the US government. A three-year pilot project, begun in 2006, focused on characterization of three types of human cancers: glioblastoma multiforme, lung, and ovarian cancer. In 2009, it expanded into phase II, which planned to complete the genomic characterization and sequence analysis of 20-25 different tumor types by 2014. TCGA surpassed that goal, characterizing 33 cancer types including 10 rare cancers. Funding is split between genome characterization centers (GCCs), which perform the sequencing, and genome data analysis centers (GDACs), which perform the bioinformatic analyses.”

This endeavor was a very complex process. “The project scheduled 500 patient samples, more than most genomics studies, and used different techniques to analyze the patient samples. Techniques include gene expression profiling, copy number variation profiling, SNP genotyping, genome wide DNA methylation profiling, microRNA profiling, and exon sequencing of at least 1,200 genes. TCGA is sequencing the entire genomes of some tumors, including at least 6,000 candidate genes and microRNA sequences. This targeted sequencing is being performed by all three sequencing centers using hybrid-capture technology. In phase II, TCGA is performing whole exon sequencing on 80% of the cases and whole genome sequencing on 80% of the cases used in the project.”

I have read a great deal about big data but have never been certain how it fit into cancer treatment. But, I have always wanted to know more.

In corresponding with other women and reading other ovarian survivors’ posts, I hear women, like the woman in this video, who want “cutting edge” treatment for their ovarian cancer first line. However, we are sometimes being cautioned not to go beyond the current “gold standard treatment.”

I’m not an oncologist or researcher, only a survivor who is hungry for both answers and hope. When I was diagnosed in 2008, I opted for adding the the experimental drug Avastin to be my “gold standard” treatment. I continued it one year afterwards and have been in remission for 9 years and never regretted that decision.

If and when I recur, with my doctors cooperation, opt for cutting edge treatment most likely using The Clearity Foundations tools to find it. However I share this view only as my opinion not that of my Doctor or The Clearity foundation.

Consequently, I watched this 30 minute video and tried to understand its very technical and nontraditional way of using principles of physics, genomics, computer modeling, genetic sequencing, and biology in considering new ways of treating cancer.  The researchers (one an ovarian cancer survivor herself)  talk about using both a combination of “stemness” (patterns of metastasis and stem cells growth) and “immune system activation processes” to treat her individual tumor.

This video or her treatment choice won’t be for everyone! But I found that reading about these researchers joint efforts gave me hope that eventually researchers will learn enough about genomics to transform first line ovarian cancer treatment from merely a generic “one fits all” treatment to a highly personal or “hybrid genetic” treatment.

I worry, however, about the funding for these studies as in 2017 when the funding for NIH and for cancer research is so uncertain.

But if “squeaky wheels do get the grease” I plan on squeaking for myself and my sister survivors for as long as possible. We must keep first line treatment for ovarian cancer moving forward!

New Study Provides BRCA Mutation Carriers Guidance For When Surgery Has Greatest Impact

New Study Provides BRCA Mutation Carriers Guidance For When Surgery Has Greatest ImpactOf the women who carry the mutated BRCA1/2 genes, 45-65 percent will develop breast cancer, and 15-39 percent will develop ovarian cancer in their lifetimes. Many women, especially those who have experienced the death of family members to these cancers, elect to undergo preventive surgeries that can significantly increase life expectancy, but require extensive recovery time and can impact later fertility and quality-of-life. However, few guidelines exist that shed light on the optimal age to undergo these procedures, and in what sequence. A new study in the INFORMS journal Decision Analysis provides insight to help enable physicians and patients make better-informed choices.

The study, “Was Angelina Jolie Right? Optimizing Cancer Prevention Strategies Among BRCA Mutation Carriers,” was conducted by Eike Nohdurft and Stefan Spinler of the Otto Beisheim School of Management, and Elisa Long, of the UCLA Anderson School of Management.

“Following Angelina Jolie’s revelation in 2013 that she carries a BRCA1 mutation and candid discussion of her own decision to under go a preventive BM and BSO two years later, studies have reported an “Angelina Jolie effect” with referrals for genetic testing increasing twofold and rates of preventative bilateral mastectomies also more than doubling,” said Eike Nohdurft.

The procedures that BRCA mutation carriers can choose to undergo include a bilateral mastectomy (BM), which involves surgically removing both breasts and reduces the lifetime risk of breast cancer by 95 percent. An additional procedure, a bilateral salpingo-oophorectomy (BSO), the removal of both ovaries and fallopian tubes, reduces risk of ovarian cancer by 80 percent and reduces breast cancer risk by an additional 60 percent. While the impact on life expectancy is significant, these invasive procedures are associated with a number of possible complications, including hormonal side effects and fertility implications.

The researchers developed a decision-analytic model that provides a timetable for women who carry these gene mutations regarding which procedures to undergo, in what order they should be conducted, and at what age they will have the greatest positive impact. According to the study results, for female carriers of a BRCA1 gene mutation, a BM is recommended between the ages of 30 and 60, followed by a BSO after the age of 40. For BRCA2 carriers, the optimal age for a BM is between 40 and 46 years and after age 49 for a BSO.

The study was motivated by one of the author’s, Elisa Long, own battle with breast cancer and subsequent discovery that she carries a BRCA1 genetic mutation. After completing treatment in 2015 and discussing whether to undergo additional preventive surgery with her doctors, she observed that no comprehensive decision-support tool existed to help patients make these difficult decisions. She partnered with Stefan Spinler and Eike Nohdurft, a visiting doctoral student, to build an evidence-based model and help fill this gap.

“This new insight will allow women to make a more informed decision for their long-term approach to cancer prevention and other mitigating factors such as family planning,” said Nohdurft.

To read this full article on ScienceDaily.com, please click here.

Roadblocks to Advancing Treatment of Rare Ovarian Cancers

Roadblocks to Advancing Treatment of Rare Ovarian CancersIt is difficult for advances to be made in rare cancers because there are fewer patients. This makes it more challenging to conduct clinical trials for these diseases. Rare ovarian cancers are no exception to this.

In an interview with CURE, David M. Gershenson, M.D., professor of Gynecologic Oncology at the University of Texas MD Anderson Cancer Center discusses the treatments available for some of these rare types, as well as what the future could look like.

Can you tell me a little about the rare types of ovarian cancer and what is important to know about them?

There are several types of ovarian cancer: malignant ovarian germ cell tumors, sex cord stromal tumors and then the rare types of epithelial tumors: ovarian clear cell carcinoma, low-grade serous carcinoma and mucinous epithelial ovarian cancer.

There are challenges and barriers to studying rare ovarian cancer. It’s very difficult to conduct clinical trials because there are fewer patients. It sometimes can take a long time to accrue patients on a clinical trial. There is also not a lot of federal funding for trials of rare cancers in general. The pharmaceutical companies are not that interested, for obvious reasons related to revenue. So, there are many challenges in trying to make advances in the study of ovarian cancers that are rare.

Also, some of these rare ovarian cancers have a number of genetic or genomic abnormalities. Unlike high-grade serous carcinoma which is the most common type, rare cancers have many abnormalities that are difficult to treat. These types have fairly specific genomic aberrations that can be, in some cases, treated with targeted agents. I think that the emphasis over the past few years has been, and in the next decade, will be on targeted agents, combinations of targeted agents, and, in some of these rare tumors, hormonal therapies. For instance, for granulosa cell tumors, a type of sex cord stromal tumor, as well as low-grade serous cancers, these are relevant. There are many different targeted treatments and new treatments that we’d like to study, but again it gets back to the challenges that we have in conducting clinical trials.

What are the current treatment options for a patient with one of these rare ovarian cancers?

It varies. For low-grade serous carcinoma, there have been first generation trials of MEK inhibitors. MEK is a gene that occurs in the MAP kinase pathway and we know that there are mutations of KRAS and BRAF that occur in that pathway. There have been a number of trials of these targeted agents, these MEK inhibitors. One has been completed, three have been done in the second-generation, the last of them is finishing accrual later this year. That’s one major area of research.

Another treatment option for low-grade serous carcinoma is hormonal therapies. We know that low-grade serous carcinoma has many features in common with ER+ breast cancer. We are studying aromatase inhibitors in upcoming trials in the neoadjuvant setting, in the recurrent setting, as well as in the frontline setting for maintenance therapy.

Clear cell cancer is another area where there are a number of aberrations in the pathways. There’s a great opportunity to study targeted agents in that area. There have been some trials and there will be future trials as well.

The other thing I would mention for clear cell cancer is immune checkpoint-inhibitor treatments. There have been some very interesting responses in clear cell cancers with immune checkpoint drugs. And there will be future trials, which are currently in development, focused on the checkpoint inhibitors.

Do these rare types of ovarian cancers have symptoms or effects on the body that differ from the most common type?

No. Most of these rare ovarian cancers have symptoms that are not really differentiated from those of women who have the most common type, which is high-grade serous. Abdominal pain, bloating, those kinds of symptoms occur at the time of diagnosis.

Some of the patients with certain types live a very long time, because the diseases are indolent. That would be true for granulosa cell tumors as well as low-grade serous carcinomas. These patients may experience side-effects from treatment. It is all related to the quality of life that they may have. Not only from cancer, but from the many treatments.

One of the areas where we’re really reducing the amount of treatment is a success story with malignant ovarian germ cell tumors. The average age at diagnosis is about 16 and up. Until the 1970s, most girls and women who had this type died of their disease. We had no good therapy. The introduction of Platinol (cisplatin) in the late 1970s completely transformed that area. Now the cure rate is 95 percent. However, these girls and women experience some of the side-effects of chemotherapy. Now, there’s a big move, and a recent clinical trial, that focuses on reduction in the surgical treatment of germ cell tumors, as well as trying to completely get rid of chemotherapy in some patients who have early-stage disease.

Sixteen is a very young age to encounter cancer. Can you discuss some of the specific concerns for those patients?

Late-effects and fertility are the two major concerns. Fortunately, for instance with germ-cell tumors and granulosa cell tumors, they are almost always unilateral, they only affect one ovary. In almost all of these patients, you can preserve a normal contralateral ovary and uterus, so you preserve their fertility. However, if the patients does receive chemotherapy, there’s about a 15 percent rate, or frequency, of acute ovarian failure, making them infertile.

Most young patients are able to preserve their fertility. We’ve conducted studies to show that many of these young patients can go on to have normal pregnancies and normal offspring. That’s good news. Once we start to reduce the amount of chemotherapy we’re using in these patients, that will be even better, because then we won’t have to face that 15 percent frequency of acute ovarian failure.

A big concern for many patients with ovarian cancer is the high rate of recurrence. Does that apply to these rare types?

It is, unfortunately. All three of the rare epithelial types: clear cell, mucinous and low-grade serous are not very sensitive to the standard chemotherapy, which is typically Abraxane (paclitaxel) and Paraplatin (carboplatin). The recurrence rate in all three of those tumors are high, in the 70 percent range.

Fortunately, low-grade serous carcinoma, despite its insensitive to chemotherapy, is an indolent disease, as is granulosa cell. Patients can still live for many years. Clear cell and mucinous are fairly aggressive types. When they recur, they’re very difficult to treat.

What would you consider to be key to advancing research on rare types of ovarian cancer?

We need a grass-roots advocacy movement to lobby not only Congress but the National Cancer Institute to put more emphasis on rare cancers, specifically rare ovarian cancers. The only way we’re going to advance treatments is to conduct clinical trials that prove that one treatment is better than the other. We really need the help of our advocates in that fight.

To read this full article on CureToday.com, please click here.

Don’t Quit

Don't QuitPam Kusar thought she had “GHD gut.” Or worse.

Anyone who’s done GHD sit-ups after a reprieve from the movement knows the feeling—getting out of bed, sneezing, laughing, crying all induce pain, if you’ve done more reps than you should have.

After her first event at her first CrossFit Games in 2015, the Masters athlete thought she had pulled a muscle doing the movement.

But the Games had ended in late July. It was September. And the pain hadn’t subsided. Kusar also noticed she had started getting up in the middle of the night to go to the bathroom.

“I thought I had a urinary tract infection,” she recounted.

So Kusar visited her gynecologist.

The truth was more sinister.

An ultrasound showed a 4-inch mass on Kusar’s ovaries. The doctor called it malignant.

“It lit all up. So, they just sent me to the oncologist.”

The specialist told Kusar she needed a hysterectomy but he wouldn’t know for certain if he’d be able to remove the entire cancerous mass until he performed the surgery.

“It was kind of a shock. I just never expected that (was) going to happen to (me).”

In October, Kusar went under the knife.

The good news: The oncologist removed the entire mass. The bad news: Six weeks of recovery lay ahead before she could begin 18 weeks of chemotherapy.

“I woke up with staples all the way up my stomach,” Kusar recounted. “When you’re (lying) in bed and your family leaves the hospital and the nurse doesn’t come and you can’t even sit up, you knew your life was gonna change for a while.”

More change was coming.

During her six weeks of recovering from her hysterectomy, doctors told Kusar she tested positive for a breast cancer gene. There was an 87 percent likelihood she, like her mother, would contract the disease. Kusar had three options: do nothing and hope she was among the 13 percent; undergo additional chemotherapy; have a double mastectomy.

Kusar opted for another surgery.

“I did not want to go through chemo again after all that,” she explained.

In May 2016, doctors removed both of her breasts.

To assume Kusar, a former bodybuilder and a former competitive powerlifter, was sedentary during that time would be wrong.

While she recovered from her first surgery, Kusar started walking around inside her house. Her husband, Jerry, had bought her a wearable activity tracker to monitor her movement.

“Within days after having a hysterectomy, she’s gettin’ 26,000 steps,” he recalled. “I mean, she’s that kind of (person). She won’t sit down.”

Until she was healed from both surgeries, walking was about the only activity Kusar could do.

“I did a lot of walking—lots of walking,” she emphasized with a laugh.

By September 2016, Kusar was in a deadlift competition; she pulled 300 lb.

“With her wig on,” Jerry noted. “She was wearing her wig back then.”

Still, by the time the CrossFit Games Open rolled around, Kusar didn’t believe she was physically ready.

“There’s thousands of people. No one cares. Just go in and do it,” Jerry told her.

Kusar ended up finishing 24th in the world in her age group, the Masters Women 55-59 Division. She placed 2nd in the Central East Region and went on to compete in the Online Qualifier, ending in 17th place overall.

“It was a big surprise,” Kusar said of qualifying for the Games.

She continued: “It was a great goal to try and do that for myself. It gave me something to work toward.”

Her goal for this year’s Games is to make it to the final event.

“That would be awesome,” Kusar said.

In 2015, she finished 6th in the 55-59 division.

Although she had her days of “getting down” during her two surgeries and chemotherapy, Kusar said she tried to take life one step at a time. First, she focused on healing from the hysterectomy. Once she started chemo, she dialed in her nutrition to ensure her blood count was back up to normal before beginning the next round of treatment. After that was done, she prepared for the mastectomy.

“I did the best I could to stay positive,” Kusar said. “I knew that lots of people go through this. You just gotta do it.”

At 5 foot 1 and 117 lb., the 57-year-old might not look imposing, but she’s tough, Jerry assured.

“She doesn’t stop. She won’t let it knock her down,” he said.

He added: “Don’t quit—that’s the message.”

To read this entire article on Games.Crossfit.com, please click here.

New Therapeutic Approach For Difficult-To-Treat Subtype Of Ovarian Cancer Identified

New Therapeutic Approach For Difficult-To-Treat Subtype Of Ovarian Cancer IdentifiedA potential new therapeutic strategy for a difficult-to-treat form of ovarian cancer has been discovered by Wistar scientists. The findings were published online in Nature Cell Biology.

Ovarian clear cell carcinoma accounts for approximately 5 to 10 percent of American ovarian cancer cases and about 20 percent of cases in Asia, ranking second as the cause of death from ovarian cancer. People with the clear cell subtype typically do not respond well to platinum-based chemotherapy, leaving limited therapeutic options for these patients.

Previous studies, including those conducted at The Wistar Institute, have revealed the role of ARID1A, a chromatin remodeling protein, in this ovarian cancer subtype. When functioning normally, ARID1A regulates expression of certain genes by altering the structure of chromatin—the complex of DNA and proteins in which DNA is packaged in our cells. This process dictates some of our cells’ behaviors and prevents them from becoming cancerous.

“Conventional chemotherapy treatments have proven an ineffective means of treating this group of ovarian cancer patients, meaning that alternative strategies based on a person’s genetic makeup must be explored,” said Rugang Zhang, Ph.D., professor and co-program leader in Wistar’s Gene Expression and Regulation Program and corresponding author of the study. “Therapeutic approaches based on the ARID1A mutation have the potential to revolutionize the way we treat these patients.”

Recent studies have shown that ARID1A is mutated in more than 50 percent of cases of ovarian clear cell carcinoma. Mutations of ARID1A and the tumor suppressor gene TP53 are mutually exclusive, meaning that patients with a mutation of ARID1A do not also carry a mutation of TP53. Despite this, the function of TP53, which protects the integrity of our genome and promotes programmed cell death, is clearly impaired as patients with the disease still have a poor prognosis.

In this study, Zhang and colleagues studied the connection between ARID1A and histone deacetylases (HDACs), a group of enzymes involved in key biological functions. They found that HDAC6 activity is essential in ARID1A-mutated ovarian cancers. They were able to show that HDAC6 is typically inhibited by ARID1A, whereas in the presence of mutated ARID1A, HDAC6 levels increase. Because HDAC6 suppresses the activity of TP53, therefore inhibiting its tumor suppressive functions, higher level of HDAC6 allow the tumor to grow and spread.

Using a small molecule drug called rocilinostat that selectively inhibits HDAC6, the Zhang lab found that by blocking the activity of the enzyme in ARID1A-mutated cancers, they were able to increase apoptosis, or programmed cell death, in only those tumor cells containing the ARID1A mutation. This correlated with a significant reduction in tumor growth, suppression of peritoneal dissemination and extension of survival of animal models carrying ARID1A-mutated ovarian tumors.

“We demonstrated that targeting HDAC6 activity using a selective inhibitor like rocilinostat represents a possible therapeutic strategy for treating ovarian clear cell carcinoma and other tumors impacted by mutated ARID1A,” said Shuai Wu, Ph.D., a postdoctoral fellow in the Zhang lab and co-first author of the study. “Inhibitors like the one we used in this study have been well-tolerated in clinical trials, so our findings may have far-reaching applications.”

To read this full article on Medical Xpress, please click here.

Combinations May Be the Future for Ovarian Cancer

Combinations May Be the Future for Ovarian CancerImmunotherapy and PARP inhibitor combinations may be the future of ovarian cancer treatment, says Samir N. Khleif, M.D.

Clinicians are seeking alternatives to chemotherapy because, despite an 80 percent response, recurrence is universal with few options available following recurrence. Ovarian cancer is an immune-dependent cancer; ovarian cancers with T-cell infiltration within the tumor microenvironment are associated with superior progression-free survival and overall survival.

Researchers have defined multiple tumor-associated antigens, and in turn, tested and developed an array of vaccines. Unfortunately, vaccines have demonstrated limited efficacy in this setting.

“Most have approached the vaccine as a single agent rather than as a combination agent, either in a specific antigen, either synthetic, naked DNA, RNA, bacterial, or viral; whole-cell lysate, or anti-idiotype vaccine and it is either given by itself or given in the context of a dendritic cell,” said Khleif, director of the Georgia Health Sciences Cancer Center in Augusta.

Ovarian cancer is an immune-driven tumor. But the tumor itself is immune-suppressive environment. As a result, T cells are activated and captured by various mechanisms, but unable to generate a proper immune response. These mechanisms include accumulation of intratumoral T regulatory cells (Tregs) that block an immune response, production of the enzyme IDO (leading to activation of suppressive populations of Tregs) by tumor cells, and suppression of effector T cells by engagement of PD-1 with PD-L1.

“When we think of our approach to vaccines, it’s pretty naïve to think that a vaccine is going to generate T cells, and the T cells are going to be taking care of a tumor that is that immune suppressive,” said Khleif.

In response, physicians and researchers have proposed using PD-1 inhibitors and other checkpoint inhibitors in ovarian cancer, but so far, the data are scant. The expression of PD-1 in ovarian tumors is dependent on the grade of the tumor, with high-grade tumors having higher expression.

In Hamanishi et al, researchers observed two complete responses and one partial response after treatment with Opdivo (nivolumab) at 1 mg/k or 3 mg/kg every two weeks in 20 patients with platinum-resistant ovarian cancer. Levels of PD-L1 expression did not seem to influence response, “which might be a little bit different than other diseases like lung cancer,” he said.

In a phase 1b study of Bavencio (avelumab) conducted by Disis et al, 10 mg/kg, in 124 patients demonstrated an objective response rate of 9.7 percent and stable disease in 44 percent. Another study of Opdivo in 17 patients with recurrent/refractory epithelial ovarian cancer, showed one partial response and two patients with stable disease after treatment.

“As a single agent, so far, we have some responses but we did not break that tolerance yet,” Khleif said, and noted that the responses rarely lasted very long.

He added that addressing the immune suppressive state of the tumor microenvironment in ovarian cancer will likely require a multiplication of effort. “That is why combination immune therapy is going to be, and is, the name of the game.”

Chemotherapy is known to induce PD-L1 expression and lead to enhanced infiltration of CD8-positive cells in the tumor, possibly enhancing the efficacy of checkpoint inhibitors.

Khleif’s team has discovered that PI3K isoforms differentially regulate Tregs and T conventional cells (Tconvs). Tregs are primarily dependent on the PI3K-delta isoform, whereas in Tconvs, PI3K-alpha and -beta provide a redundant pathway to PI3K-delta. This dichotomy can be exploited to target Tregs by inhibiting the PI3K-delta isoform while leaving Tconvs intact.

Co-administration of an inhibitor of PI3K-delta with a tumor-specific vaccine decreased the number of suppressive Tregs and increased the number of vaccine-induced CD8 T cells within the tumor microenvironment in a mouse model of lung cancer, resulting in a large reduction in tumor volume. The authors concluded that these findings “offer a mechanistic rationale to employ PI3K-delta inhibitors to selectively target Tregs and improve cancer immunotherapy.”

PARP has emerged as an important target in ovarian cancer. PARP inhibitors have been shown to have clear beneficial effects on clinical outcomes in the treatment of ovarian cancer in several clinical trials. The combination of a PARP inhibitor with CTLA-4 blockade improved overall survival in a BRCA1-deficient murine ovarian cancer model compared with treatment with CTLA-4 or PD-1/PD-L1 monoclonal antibodies alone.

In results published by Clinical Cancer Research earlier this year, PARP inhibitor enhanced apoptosis and tumor volume shrinkage within the tumor microenvironment when given in addition to a PD-1/PD-L1 blocker. PARP inhibition attenuated anticancer immunity via upregulation of PD-L1, and blockade of PD-L1 re-sensitized the PARP inhibitor-treated cancer cells to T-cell killing, the authors found.

Khleif added that multiple trials combining PARP inhibitors and checkpoint inhibitors are ongoing.

To read this full article on CureToday.com, please click here.

‘No’ Yet Again to Routine Ovarian Cancer Screening

'No' Yet Again to Routine Ovarian Cancer ScreeningNew draft guidelines from the US Preventive Services Task Force (Task Force) recommend against screening for ovarian cancer in women who have no signs or symptoms.

“The Task Force found that screening women without signs or symptoms for ovarian cancer does not decrease the number of deaths from the disease and may lead to unnecessary surgeries,” said Task Force member Maureen Phipps, MD, MPH, in a statement.

“Therefore, the Task Force recommends against screening for ovarian cancer in women who have no signs or symptoms and who are not at high risk for ovarian cancer,” she said.

This recommendation applies only to asymptomatic women who are not deemed to be at a higher risk of developing ovarian cancer. It does not pertain to woman who are known to be at higher risk, such as those who harbor BRCA mutations.

Overall, the Task Force found adequate evidence that routine screening in asymptomatic women or in those not deemed to be at high risk did not decrease ovarian cancer mortality.

There was also evidence that the harms associated with screening were at least moderate and in some cases could be substantial and that there was “at least moderate certainty” that the potential harms outweighed the potential benefits. These harms include false positive results, which could lead to diagnostic surgery and potential removal of the ovaries and fallopian tubes.

The recommendations in the new draft paper are consistent with the previous recommendation for ovarian cancer, which was issued in 2012 and gave routine screening a grade D recommendation (ie, not recommended).

The 2012 report, in turn, echoed a 2004 recommendation made by the Task Force, which found that “the potential harms outweighed the potential benefits of screening.”

No Mortality Benefit

In their review of available data, the Task Force identified three good-quality studies that evaluated the effect of annual screening in asymptomatic women who were not deemed to be at a high risk of developing ovarian cancer. None of the findings demonstrated that screening significantly reduced ovarian cancer mortality.

The United Kingdom Collaborative Trial of Ovarian Cancer Screening, which is the largest and most recent trial, was conducted after the initial 2012 recommendations were issued. It confirmed the findings from the earlier Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial that screening does not decrease mortality in this population.

Data from the three studies, along with a fourth fair-quality study that examined quality of life and the psychological harms of screening (Quality of life, Education, and Screening Trial) were analyzed to determine the risks associated with screening.

Calculated false positive rates of the various screening methods ranged from 4.2% to 44.2%; from 0.2% to 3.2% of patients eventually underwent surgery. Among this group, major surgical complications were observed in 0% to 15%.

In Sync With Other Groups

Ovarian cancer screening for the general population is not recommended by any of the major medical and public health organizations. The American College of Obstetricians and Gynecologists, the American Cancer Society, and the American College of Radiology do not recommend screening for women at average risk. The American Academy of Family Physicians (AAFP) also recommended against screening in 2012; the AAFP is currently reviewing this recommendation.

To read this entire article on Medscape.com, please click here.