Global Vs. Local

By: Annette McElhiney Global Vs. Local

Typically, as an advocate and a Clearity patient, I write about ovarian cancer and subjects that would interest women in the United States.

However, in my professional life, I am working with former colleagues and students on writing a chapter for a reference book on Global Women’s Health for those ages 16 to 24. The countries included are divided regionally suggested by the World Health Organization. Because I have a 16 year old adopted South Korean grandson, I chose to write about Central Asia, more specifically Japan, South Korea, China and Russia.

However, contemplating the parallels between my work on this reference book and my advocacy for Clearity I recognize that as a woman who lives in the US, I have a privileged situation as do many other women.

Most of us have clean water, nutritional food, the freedom to marry or not marry whom we choose, a safe environment, access to public education, an opportunity to grow up in families with our siblings, and the ability to work as a free agent. We also still have the right to control how many children we bear.

March is Women’s History Month — a time when I think of women collectively, not personally. Consequently, I’m also reminded of the divisions that arise in healthcare in the U.S. as a result of insufficient money and access to healthcare.

As I try to connect with ovarian cancer survivors on Facebook and various social media outlets, I’m compelled to read the stories of women who don’t have insurance and cannot afford the tests for cancer, genetic tests, the necessary surgical follow-up procedures like CT or PET scans, and expensive chemotherapy. Their stories remind me of the great need we have in the U.S. for affordable healthcare.  I’m frightened that the Affordable Health Care Act — which has helped so many who don’t have health insurance through their employer — will be dismantled.

I’m outraged that Planned Parenthood is being defunded. Most people think Planned Parenthood is active only in birth control, STDs and abortion services, but that is not the case. They are active in screening for cancer as well! In fact most of their services are in screening and preventative health. For many women who don’t have health insurance, Planned Parenthood is be their only option for mammograms, Pap smears, and much more.

In addition, I’m acutely aware of the role of access to progressive health care.  If an ovarian cancer survivor lives close to an urban academic center offering the latest treatment and clinical trials, she is more likely to take advantage of them. Such is not always the case for survivors who live in isolated or rural communities.

Another area affected is ovarian cancer survivors who lack access to support groups or counseling services. In urban areas specifically, it is often difficult to find support groups specific to our disease. Finally, state-run organizations may offer information, guidance, counseling and even financial help. However, this is not always the case for women in many rural areas.

This confirms why I am an advocate for The Clearity Foundation. Clearity exists only to assist ovarian cancer survivors. Clearity conducts its own research and shares the most current information on treatment and clinical trials. Their consultants guide survivors through accessing and choosing the most appropriate clinical trial. For those survivors who are fortunate enough to have insurance, their insurance may pay for molecular profiles and guidance through selecting clinical trials. However, if survivors who qualify for profiles don’t have insurance, Clearity will deliver the service free of charge.

I’ve been extremely fortunate to have had the latest and best treatment. I have insurance and a strong supportive network. Because I’ve been so fortunate, I want other women to have the same kind of excellent care. Consequently, I hope those of you reading this will join me in whatever way you can, in working for the best treatment and experience for all ovarian cancer survivors.


PapSEEK: Potential Screening Test for Gynecologic Cancers

PapSEEK: Potential Screening Test for Gynecologic CancersA sample obtained from routine Papanicolaou (Pap) tests used for cervical cancer screening can be subjected to a multiplex panel test, dubbed PapSEEK, to determine whether the sample is positive for endometrial or ovarian cancer, two gynecologic cancers for which early detection has been a problem.

The new test is described in a study published online March 21 in Science Translational Medicine.

“PapSEEK adds another dimension to screening for gynecologic cancers,” write the authors, led by Yuxuan Wang of the Ludwig Center for Cancer Genetics and Therapeutics and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland. Earlier this year, some of these researchers reported on the CancerSEEK test for eight common cancers, as reported by Medscape Medical News.

PapSEEK: Potential Screening Test for Gynecologic Cancers

The PapSEEK test includes a mutational analysis of 18 genes using a multiplex panel and an analysis for aneuploidy.

Using different approaches to collect the Pap sample, the test identified endometrial cancer in 81% to 93% of cases and ovarian cancer in 33% and 63% of cases, with nearly no false positive results (0 to 1.4%) in healthy control persons.

“Our study lays the foundation for evaluating PapSEEK in a large prospective study,” Wang and colleagues write. They indicate that the most natural cohort for this test would be women who are at high risk for gynecologic cancers, owing to hereditary factors, obesity, or symptoms such as postmenopausal or uterine bleeding.

The utility of PapSEEK lies in its ability to identify difficult-to-detect endometrial and ovarian cancers at an early stage using a sample obtained from a routine Pap test, they comment. Current tests, such as transvaginal ultrasound, are invasive and result in many false positive results. Moreover, they are neither ideal nor recommended as a screening tool in the general population, Wang and colleagues point out.

Details of the PapSEEK Test

Wang and colleagues analyzed samples from 1658 individuals — 656 with endometrial or ovarian cancer, and 1002 healthy control persons.

They took advantage of the fact that endometrial and ovarian cancer cells collect in the endocervical canal, where they can be collected with a Pap brush. The brush is then dipped into a preservative fluid, and cells are applied to a slide for a cytologic examination of the classical Pap smear and for the PapSEEK test.

The researchers isolated DNA from the cells using a sensitive polymerase chain reaction (PCR) error-reduction technology called Safe-Sequencing System to identify mutations across 18 genes. They also determined aneuploidy using a PCR-based method to amplify ~30,000 loci to determine gains or losses on chromosomal arms.

They then used two separate methods to increase the sensitivity of the test. In one approach, they used a “Tao” brush that allows for interuterine sampling closer to the anatomic sites of the tumor. In the second approach, they undertook mutational analyses of circulating tumor DNA obtained from liquid biopsies.


Of the 328 women with endometrial cancer, 81% Pap brush samples tested positive. Of these, 78% were cases of early-stage cancer, and 89% were cases of late-stage disease. PTEN and TP53 were the most common mutations, seen in 64% and 41% of samples, respectively.

Of the 245 women with ovarian cancer, 29% Pap brush samples tested positive. Of these, 28% were cases of early-stage disease, and 30% were cases of late-stage disease. TP53 was the gene most frequently mutated (74%).

Wang and colleagues found aneuploidy in 38% of endometrial and 11% of ovarian Pap brush samples.

Taken together, the PapSEEK test from Pap brush samples detected endometrial and ovarian cancer in 81% and 33% of endometrial and ovarian cancers, respectively.

Of the 714 women without cancer, only 1.4% of samples were positive with the PapSEEK test, providing a high specificity of ~99%.

Tao brush samples were collected from 123 patients with endometrial cancer, 51 patients with ovarian cancer, and 125 women without cancer.

Using the PapSEEK test for Tao brush samples, the detection rate increased for both endometrial (93%) and ovarian cancer (45%). Mutations were consistent with those seen in Pap brush samples. Remarkably, none of Tao brush samples of the women without cancer tested positive — a specificity of 100%.

Eighty-three women with ovarian cancer had provided Pap brush samples and plasma samples. PapSEEK was positive for 40% of Pap brush samples; 43% of plasma samples showed mutations in circulating tumor DNA, with partial overlaps. Thus, using at least one of the two tests, 63% of samples tested positive for ovarian cancer.

Clinical Utility

Wang and colleagues note that large prospective studies are required to validate observations from this retrospective analysis.

These studies will need to answer several questions, the authors concede. Is Tao brush sampling superior to Pap brush sampling? The researchers explain that the Tao brush, which has been approved by the US Food and Drug Administration, allows sampling of the entire endometrial cavity without injury to the myometrium or contamination from the cervical canal. It can be used in the outpatient setting without anesthesia; “for a potential screening test, it is well tolerated,” they comment.

Among the issues that need to be addressed is the question of whether PapSEEK would be used along with other approaches, such as serial CA-125 testing or liquid biopsies. Another question concerns the best clinical management of women who test positive with PapSEEK. Also unknown is the interval to use between tests.

The authors indicate that the cost of PapSEEK would be higher than that for a Pap smear; the cost would be comparable to that for colonoscopy, mammography, and CT imaging.

The researchers are optimistic, and their conclusion is upbeat. “PapSEEK adds another dimension to screening for gynecologic cancers,” Wang and colleagues conclude.

To read this full article on, please click here.

Possible Hereditary Link Between Ovarian and Testicular Cancers Observed

Possible Hereditary Link Between Ovarian and Testicular Cancers ObservedA registry study suggests that there may be a familial association between ovarian and testicular cancers. In the study, men with testicular cancer were more likely to have a mother with ovarian cancer compared with men with other malignancies.

Testicular germ cell tumors (TGCT) are the most common malignancies among American men aged 15 to 44 years; family history of TGCT has been well established as a risk factor for these tumors. “Although familial TGCT studies have yet to characterize TGCT syndromic patterns, a biologically plausible link between TGCT and ovarian germ cell tumors has been posited,” wrote study authors led by Kirsten B. Moysich, PhD, of the Roswell Park Comprehensive Cancer Center in Buffalo.

The investigators conducted a study using data from the Familial Ovarian Cancer Registry to test for associations between ovarian cancer and TGCT. They included a total of 2,636 families with multiple cases of ovarian cancer. Results were published in Cancer Epidemiology.

The cohort contained 34 men with testicular cancer, and 2,894 men with non-testicular cancers. Of those 34 men, 24 had mothers with known ovarian cancer status, and 10 mothers (41.67%) had ovarian cancer while 14 did not. This meant that the men with testicular cancer were significantly more likely to have a mother with ovarian cancer compared with the men with other malignancies, with an odds ratio (OR) of 3.32 (95% CI, 1.46–7.55; P = .004). The same was true for having a sister with ovarian cancer, though this did not reach significance, with an OR of 1.66 (95% CI, 0.87–3.15; P = .124); of the 43 sisters of men with testicular cancer with known ovarian cancer status, 14 (32.56%) had ovarian cancer.

The men in the registry with testicular cancer fathered 13 daughters, but these daughters were either too young to be at risk for ovarian cancer, or lacked adequate follow-up. Four of 16 maternal grandmothers had ovarian cancer (25%), and none of 9 paternal grandmothers with known status had the malignancy.

The mechanism for this connection may involve X-chromosome–linked susceptibility genes, the authors wrote. “While the observed absence of ovarian cancer in paternal grandmothers of men with testicular cancer is consistent with X-linked transmission, analyses were limited by small sample sizes and X-linkage could not be conclusively established,” they noted.

An attempt to update the registry and improve the family histories and collection of biospecimens is underway, specifically in families with multiple cases of ovarian cancer as well as at least one case of testicular cancer. “These analyses may provide insight into the etiology of transmission patterns of both cancers and expose novel gene targets for prevention and therapy,” the authors wrote.

To read this full article on Cancer Network, please click here.

Despite Showing Interest, Vulnerable Populations Lack Sufficient Clinical Trial Information

Despite Showing Interest, Vulnerable Populations Lack Sufficient Clinical Trial InformationDespite showing an interest in clinical trials and biobanking, underserved populations appear to be unclear on how to learn about them, while community physicians reported lacking appropriate information to give them, according to data to be presented at the American Association for Cancer Research (AACR) Annual Meeting.

Vulnerable populations – those who experience cancer health disparities such as racial and ethnic minority groups, individuals with low socioeconomic status and those who live in rural areas – are often underrepresented in clinical trials and biobanking. For example, less than 5 percent of patients with cancer are enrolled in a clinical trial, of which less than 10 percent are minorities.

“We must have diverse participation to identify how specific drugs and treatments are most useful for different people,” Terry C. Davis, Ph.D., professor of Medicine and Pediatrics at Louisiana State University Health Sciences Center and the Feist-Weiller Cancer Center, said during the AACR Annual Meeting media preview webinar. “Effective strategies are needed to help unrepresented populations get understandable information and see the value in participating in clinical trials.”

Davis, who is also the director of the Health Literacy Core of the Louisiana Clinical & Translational Science Center, attributed this problem to widening gaps in communication and knowledge.

“There is a communication problem,” she added. “Precision medicine and genomic testing initiatives are creating a widening gap in the novel space of researchers, community providers and patients and the public. Researchers often assume that patients and community providers know more than they do about clinical trials and understand all of our jargon.”

Davis and colleagues conducted 14 focus groups and seven individual interviews to identify awareness, understanding, trust and acceptance of clinical trials, while also trying to elicit input in crafting clear, culturally appropriate messages and recruitment strategies for patients. These focus groups and interviews included rural and urban patients and providers in safety-net primary care and oncology settings, and also patients in social, faith-based and support groups.

In total 103 individuals from Louisiana participated, including 78 clinic patient and community participants and 25 providers. Of the 78 community participants, 24 percent lived in rural areas, 78 percent were African-American and 70 percent reported having low incomes. Of the providers, 10 were physicians, seven were clinical research associates, five were nurse practitioners and three were behavioral health professionals.

Discrepancies between terminology appeared to be a recurring problem among participants. For example, researchers say clinical trials, whereas the participants simply called them studies. Similarly, researchers say biobanking, whereas those surveyed better understood saying, “your blood or tissue will be stored in a bank.”

When researchers mentioned the term “genomics,” participants felt that it sounded intimidating and alarming, and the term did not resonate or mean anything to most.

African American participants reported that messages regarding these trials and biobanks needed to convey the incorporation of all races and ethnicities. For example, rather than a message saying, “Minorities are needed in clinical trials – most treatments based on studies with majority of white participants,” they would rather hear, “All people are needed for studies to improve treatments and find cures.” The difference between the wording of both messages raised suspicions in these individuals.

In particular, individuals wanted to know the following: What are you going to do with my blood sample; how much information about ‘me’ are you going to keep; and what is it going to be used for?

Despite being told of protection and confidentiality, some participants still raised concerns around patient privacy, in particular, because it could become a barrier to jobs or insurance.

Overall, almost all of the participants stated they were open to participating in clinical trials and biobanking, especially in learning about studies focused on a disease they or their family had. Interestingly, low income and minority patients said were open to these options even if it would not benefit them directly.

However, only two patients with cancer reported they were previously asked about participating in a clinical trial by their physician.

The researchers noted that community participants were less trusting of clinical trials than patients were. All of the participants said that information and recommendations for clinical trials and biobanking would be most effective and actionable if it came from a trusted physician.

Participants also reported that transportation to academic centers was a barrier to their involvement in clinical trials and biobanking, but “mobile health vans could enhance participation,” Davis said.

Urban and rural providers also showed an interest in being more involved in clinical trials, but admitted they lacked the time it takes to identify trials and explain them to patients.

As a result, providers said that receiving brief, plain language handouts with talking points and a card to give patients to call for more information would be helpful in increasing participation.

Lastly, very few patients, caregivers or providers said they looked for clinical trials on the internet or social media.

“Communication needs to be easy to get your hands on. It needs to be honest and transparent. It needs to be easy to understand and actionable. What is it that we want patients to know and do?” said Davis.

Since this study was only conducted in Louisiana among select underserved populations, Davis noted additional studies are needed where researchers also speak with individuals from more diverse communities, such as additional rural areas and those in Hispanic and non-English speaking communities.

At the end of the presentation, AACR President Michael Caligiuri, M.D., President and Physician-in-Chief at City of Hope National Medical Center, commended the study, highlighting that “this is a very complex issue in terms of the barriers that really contribute to us not providing equal access, and therefore, in many cases, equal care to these underserved groups.”

To read this entire article on CURE, please click here.

Immunotherapy Raises the Stakes and Ovarian Cancer Blinks

Immunotherapy Raises the Stakes and Ovarian Cancer Blinks“I’ll see your neoepitope and raise you a tumor-infiltrating lymphocyte.” Such bets could be placed more confidently if cancer immunotherapy would deal itself a stronger hand, one that would include the “juiciest” T cells—the T cells that are best at recognizing and killing cancer cells.

Unfortunately, the juiciest T cells often get lost in the shuffle. Either they don’t reach the bloodstream, where many T cells intended for cell-based immunotherapy are drawn, or they end up at the bottom of the tumor-infiltrating lymphocyte (TIL) deck. Not content to play the hand they were dealt, scientists at the Ludwig Institute for Cancer Research decided that a little bottom dealing might be in order.

“We developed a new methodology to identify highly reactive TILs and expand them in a manner that, rather than diluting the juiciest TILs, enriches them instead,” said Alexandre Harari, Ph.D., a Ludwig Lausanne investigator and a co-leader of a new study that aims to improve personalized cancer immunotherapy. “This allowed us to compare the activity of TILs that target neoepitopes with their counterparts in the peripheral bloodstream.”

The new study was detailed in a study that appeared March 15 in Nature Communications, in an article entitled “Sensitive and Frequent Identification of High Avidity Neo-Epitope Specific CD8+ T Cells in Immunotherapy-Naive Ovarian Cancer.” This article explains that ovarian tumors, which have tended to resist cell-based immunotherapies, harbor highly reactive killer T cells that can be identified and selectively grown.

“Tumors whose cells tend to be highly mutated, like those of melanoma and lung cancer, are the ones that respond best to immunotherapies,” noted Harari. “It has long been a question whether we’d even be able to detect sufficiently mutation-reactive T cells in patients with tumors that have low mutational loads.”

Ovarian tumors have a low mutational load. In a sense, they keep their cards close to their vest. Nonetheless, they are infiltrated with mutation-sensitive T cells.

Cancer cells that have a relatively large number of mutations in their DNA express aberrant proteins—or neoantigens—that reveal the cancer to the immune system. Killer T cells recognize tiny, mutated bits of these antigens, known as neoepitopes. But neoepitopes vary wildly from patient to patient, even within the same type of cancer. This has long stymied efforts to develop generally effective therapies that target cancer antigens.

“Comprehensive and deep analysis of circulating and tumor-infiltrating lymphocytes (TILs) for neoepitope specific CD8+ T cells has allowed prompt identification of oligoclonal and polyfunctional such cells from most immunotherapy-naive patients with advanced epithelial ovarian cancer studied,” the article’s authors wrote. “Neoepitope recognition is discordant between circulating T cells and TILs, and is more likely to be found among TILs, which display higher functional avidity and unique TCRs [T-cell receptors] with higher predicted affinity than their blood counterparts.”

Essentially, the researchers developed a new way to select and expand T cells from patients that best target a patient’s cancer and then reinfuse them into the patient. The researchers also showed that killer T cells isolated from ovarian tumors using their method are much better at both recognizing neoepitopes than are those isolated from blood.

“Our results,” the authors asserted, “imply that identification of neoepitope specific CD8+ T cells is achievable even in tumors with relatively low number of somatic mutations, and neoepitope validation in TILs extends opportunities for mutanome-based personalized immunotherapies to such tumors.”

“We could even compare T cells from the two compartments targeting the exact same mutation and show that the TILs were more functional than the T cells we collected from the peripheral bloodstream,” noted Harari.

Notably, the researchers found that, using their methods, highly reactive TILs could be obtained from some 90% of the ovarian cancer patients whose tumor samples they examined.

“The big message,” added George Coukos, M.D., Ph.D., study co-leader and director of the Ludwig Institute for Cancer Research, Lausanne, “is that future cell-based therapies can be envisioned for low-mutational-load tumors and should prioritize the use of TILs over T cells collected from peripheral blood. This novel strategy to obtain enriched TILs also offers great therapeutic opportunities.”

To read this full article on, please click here.

Metformin, Statins Not Linked With Ovarian Cancer Risk in Diabetic Patients

Metformin, Statins Not Linked With Ovarian Cancer Risk in Diabetic PatientsA large retrospective cohort study found no association between the use of metformin or statins and the incidence of ovarian cancer in women with type 2 diabetes.

“People who have type 2 diabetes have been reported to have an increased incidence of various cancers, including ovarian cancer, compared with those without diabetes, the risk being highest in insulin-treated patients,” wrote study authors led by Elina Urpilainen, of the University of Oulu in Finland. Metformin, commonly used to treat type 2 diabetes, has been linked with lower incidence of several cancer types, including ovarian cancer. Statins, widely used to treat the cardiovascular diseases associated with type 2 diabetes, also may have a cancer protective effect.

The new study examined these potential effects in a cohort of 137,643 women over 40 years old and diagnosed with type 2 diabetes in Finland between 1996 and 2011; it covered a total follow-up of 748,282 person-years at risk, with a mean follow-up of 5.4 years. The results were published in BJOG: An International Journal of Obstetrics and Gynaecology.

Over the follow-up period, 303 women were diagnosed with epithelial ovarian cancer. The incidence rate was highest in the oldest age group (60–69 years), at 51.4 per 100,000 person-years, and in the group with the longest duration of diabetes (5–8 years), at 52.5 per 100,000 person-years.

The investigators conducted a case-control analysis that included 6,060 controls matched for age and type 2 diabetes duration with the 303 cancer cases. Approximately two-thirds of both cases and controls were ever-users of metformin, and just over 50% were ever-users of statins.

In the full cohort, metformin use had a hazard ratio (HR) for ovarian cancer of 1.02 (95% CI, 0.72–1.45). In the case-control analysis, the HR was 0.91 (95% CI, 0.61–1.34). For statins, in the full cohort, the HR for ovarian cancer was 0.99 (95% CI, 0.78–1.25), and in the case-control analysis it was 0.96 (95% CI, 0.75–1.23). For insulin use, the HR in the full cohort was 1.19 (95% CI, 0.73–1.93), and in the case-control analysis it was 1.19 (95% CI, 0.72–1.97). The authors noted that there was also no trend with respect to rising cumulative use of metformin or statins.

They also pointed out several limitations to the study, including a lack of information on family history, parity of the women included, and data on BMI or other markers of insulin resistance. Still, the comprehensive national registers used are considered very reliable, they noted.

“We found no evidence of an association between metformin or other forms of oral antidiabetic medication and the incidence of epithelial ovarian cancer in women aged 40 years or older with type 2 diabetes,” they concluded.

To read this full article on, please click here.

U.S. To Cover Advanced Genomic Testing For Medicare Cancer Patients

U.S. To Cover Advanced Genomic Testing For Medicare Cancer PatientsThe U.S. government said on Friday it will pay for certain genetic tests for Medicare-eligible patients with advanced cancer, in a bid to help match patients with the drugs most likely to provide benefit.

The Centers for Medicare & Medicaid Services (CMS) said that diagnostic laboratory tests using Next Generation Sequencing (NGS) would be covered by the government healthcare program.

The National Coverage Determination (NCD) is an important step in the advance of so-called personalized medicine and follows U.S. Food and Drug Administration approvals of the tests.

“We want cancer patients to have enhanced access and expanded coverage when it comes to innovative diagnostics that can help them in new and better ways,” CMS Administrator Seema Verma said in a statement.

With the decision, one small test sample from a Medicare patient with advanced breast cancer, for example, could be simultaneously screened for all known gene mutations associated with potential treatments.

When a known cancer mutation cannot be matched to an approved treatment, results from the test using NGS can help determine a patient’s candidacy for clinical trials linked to their specific mutation.

The decision covers Foundation Medicine Inc’s FoundationOne CDx in vitro diagnostic test that can detect gene mutations associated with 15 already-approved targeted cancer drugs, such as Pfizer Inc’s Xalkori for lung cancer, as well as mutations in 324 genes and two genomic signatures in any solid tumor, CMS said.

It also covers other FDA-approved in vitro diagnostics if the test has an FDA-approved use in a patient’s cancer and results are provided to the treating physician with a report to specify treatment options.

Thermo Fisher Scientific said its approved NGS, called Oncomine Dx Target Test, will be covered under the CMS decision. The test screens for a wide variety of biomarkers and gene mutations associated with non-small cell lung cancer.

Tests that gain FDA approval or clearance as an in vitro companion diagnostic in future will automatically receive full coverage under this final NCD, CMS said.

The decision also extends coverage to repeat testing when a Medicare patient has a new primary diagnosis of cancer.

To read this full article on, please click here.