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Promising Screening Tool for Early Detection of Ovarian Cancer

Evaluating its change over time, CA-125, the protein long-recognized for predicting ovarian cancer recurrence, now shows promise as a screening tool for early-stage disease, according to researchers at The University of Texas MD Anderson Cancer Center.

The updated findings are published in Cancer; preliminary data were first presented at the 2010 American Society of Clinical Oncology (ASCO) annual meeting. If a larger study shows survival benefit, the simple blood test could offer a much-needed screening tool to detect ovarian cancer in its early stages – even in the most aggressive forms – in post-menopausal women at average risk for the disease.

MD Anderson has a long history in the research of the important biomarker. In the 1980s, Robert Bast, M.D., vice president for translational research at MD Anderson and co-investigator on the ASCO study, discovered CA-125 and its predictive value of ovarian cancer recurrence. Since then, researchers at MD Anderson and beyond have been trying to determine its role in early disease detection. The marker, however, can become elevated for reasons other than ovarian cancer, leading to false positives in early screening.

“Over the last ten years, there’s been a lot of excitement over new markers and technologies in ovarian cancer,” said Karen Lu, M.D., professor and chair, Department of Gynecologic Oncology and the study’s corresponding author. “I and other scientists in the gynecologic oncology community thought we would ultimately find a better marker than CA-125 for the early detection of the disease. After looking at new markers and testing them head-to-head in strong, scientific studies, we found no marker better than CA-125.”

According to the American Cancer Society, 22,240 women will be diagnosed with ovarian cancer in 2013 and another 14,030 are expected to die from the disease. The challenge, explained Lu, is that more than 70 percent of women with ovarian cancer are diagnosed with advanced disease.

“Finding a screening mechanism would be the Holy Grail in the fight against ovarian cancer, because when caught early it is not just treatable, but curable,” said Lu, also the trial’s principal investigator.

For the prospective, single-arm, 11-year study, 4,051 women were enrolled from seven sites across the country, with MD Anderson serving as the lead site. All were healthy, post-menopausal women, ages 50-74, with no strong family history of breast or ovarian cancer. The study’s primary endpoint was specificity, or few false positives. In addition, the study looked at the positive predictive value, or the number of operations required to detect a case of ovarian cancer.

Each woman received a baseline CA-125 blood-test. Using the Risk of Ovarian Cancer Algorithm (ROCA), a mathematical model based on the patient’s age and CA-125 score, women were stratified to one of three risks groups, with the respective follow-up: “low,” came back in a year for a follow-up blood test; “intermediate,” further monitoring with repeat CA-125 blood test in three months; and “high,” referred to receive transvaginal sonography (TVS) and to see a gynecologic oncologist.

Based on the women’s CA-125 change over time, the average annual rate of referral to the intermediate and high groups were 5.8 percent and .9 percent, respectively. Cumulatively, 117 women (2.9 percent) were determined to be high risk, and thereby received the TVS and were referred to a gynecologic oncologist. Of those women, 10 underwent surgery: four had invasive ovarian cancer; two had borderline disease; one had endometrial cancer and three had benign ovarian tumors – a positive predictive value of 40 percent, which greatly surpasses the clinical benchmark of 10 percent, say the researchers. The specificity of the test was 99.9 percent, explained Lu. The screening failed to detect two borderline ovarian cancers.

Of great importance, said Lu, is that the four invasive ovarian cancers detected were high-grade epithelial tumors, the most aggressive form of the disease, and were caught early (stage IC or IIB), when the disease is not only treatable, but most often curable. Lu also noted that all four women found to have invasive disease were monitored at low risk for three years or more prior to a rising CA-125.

“CA-125 is shed by only 80 percent of ovarian cancers,” explained Bast, the study’s senior author. “At present, we are planning a second trial that will evaluate a panel with four blood tests including CA-125 to detect the cancers we may otherwise miss with CA-125 alone. The current strategy is not perfect, but it appears to be a promising first step.”

While encouraging, the findings are neither definitive, nor immediately practice-changing, stressed Lu; who also said a large, randomized prospective screening trial still needs to be conducted. Such research is ongoing in the United Kingdom; results from more than 200,000 women should be known by 2015.

“As a clinician treating women with this disease for more than ten years, I’ve become an admitted skeptic of ovarian cancer screening. Now, with these findings, I’m cautiously optimistic that in the not too distant future, we may be able to offer a screening method that can detect the disease in its earliest, curable stages and make a difference in the lives of women with this now-devastating disease.”

The study is continuing; and, as follow-up, Lu and her team plan to look at combining other markers with CA-125 to determine the screening impact of their combined change over time.

The study was supported by the National Cancer Institute, and was a research project of MD Anderson’s ovarian cancer Specialized Program of Research Excellence (SPORE), NCI P50 CA83639, the Bioinformatics Shared Resources of MD Anderson CCSG NCI P30 CA16672, the National Foundation for Cancer Research. It has also received philanthropic funds from Golfers Against Cancer, the Tracy Jo Wilson Ovarian Cancer Foundation, the Mossy Foundation, the Norton family and Stuart and Gaye Lynn Zarrow.

In addition to Lu, and Bast, other authors on the study include: Therese Bevers, M.D. Department of Clinical Cancer Prevention, Herbert Fritsche, Ph.D., Department of Laboratory Medicine, Deepak Bedi, M.D., Department of Diagnostic Radiology, Michael T. Deavers, M.D., Department of Pathology and Clinical Pathology; Charlotte Sun, Dr.PH, Department of Gynecologic Oncology, Mary A. Hernandez, Office of Translational Research, all with MD Anderson; Steven Skates, Ph.D., Massachusetts General Hospital and Harvard Medical School; Olasunkanmi Adeyinka, M.D., UT Physicians Family Physicians; William Newland, M.D., The Iowa Clinic; Richard Moore, M.D. and Cornelius Granai, M.D., both with Women & Infants Hospital, Brown University; Leroy Leeds, M.D., OGA Medical Center; Steven Harris, M.D., OB/GYN Associates of Dallas; Jeremy Geffen, M.D., Geffen Cancer Research Institute; and Nora Horick, Harvard Medical School and Massachusetts General Hospital.

As a co-inventor of the CA-125, Bast receives royalties from, and has served as an advisor to, Fujirebio Diagnostics, Inc.

Study: A 2-stage ovarian cancer screening strategy using the Risk of Ovarian Cancer Algorithm (ROCA) identifies early-stage incident cancers and demonstrates high positive predictive value [Cancer]

Source: MD Anderson Cancer Center

New Test Assesses Gestational Diabetes Risk Early in Pregnancy

Levels of a biomarker in a pregnant woman’s blood can help physicians gauge her risk of developing gestational diabetes during the first trimester, according to a recent study accepted for publication in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism (JCEM).

Gestational diabetes is a form of diabetes that can develop during pregnancy, often during the second trimester. The condition causes glucose levels in the bloodstream to be higher than normal. Early diagnosis and treatment can help the woman manage the condition. If left untreated, high blood glucose in the mother increases the risk of jaundice, breathing and hypoglycemia problems in the newborn. Uncontrolled gestational diabetes also can increase the risk of premature delivery and preeclampsia, or pregnancy-induced high blood pressure.

“Although it is important to quickly intervene in cases of gestational diabetes, often only women who have risk factors like a family history or obesity are screened early in pregnancy,” said one of the study’s authors, Atsuhiro Ichihara, MD, PhD, of Tokyo Women’s Medical University. “Women who don’t have the traditional risk factors may not be diagnosed until the second trimester. The method identified in this study offers every pregnant woman the opportunity to know her risk early on.”

The prospective cohort study tested the blood of 716 pregnant women during the first trimester to measure their levels of the soluble (pro)renin receptor, or s(P)RR. Of the participants, 44 women developed gestational diabetes.

Researchers found pregnant women with elevated s(P)RR levels were more likely to be diagnosed with gestational diabetes. Women who had the highest s(P)RR levels were 2.9 times more likely to develop gestational diabetes than women who had the lowest levels.

“In addition to gestational diabetes, recent studies have found elevated s(P)RR levels are associated with the birth of larger babies and high blood pressure in late pregnancy,” Ichihara said. “The evidence suggests the biomarker is important in the interaction between mother and fetus during pregnancy.”

Source: Prediction of Gestational Diabetes Mellitus by Soluble (Pro)Renin Receptor during the First Trimester

Source: EurekAlert!

Genophen Taps NextBio Clinical to Incorporate Genomic Data into Disease Risk Software

NextBio recently announced that it has formed a partnership with Genophen, a Stanford University spinout, which will focus on generating personalized disease prevention and wellness plans for patients based on a combination of genomic, clinical, environmental, and behavioral data.

Specifically, Genophen is partnering with NextBio so that it can use the NextBio Clinical platform to analyze genetic variants from whole genome sequence data and combine these with information on things like diet, family history, and exercise to create bespoke disease prevention plans for patients.

Genophen’s President and CEO Hossein Fakhrai-Rad told BioInform that the company tapped NextBio’s platform because it offered access to a curated database of genomic variants that are associated with various disease conditions, and because it expands Genophen’s own internally built repository. The arrangement also lets Genophen focus its efforts on disease risk assessment rather than spend time going through the literature and linking variants and diseases, he said.

Founded in 2008 at the Stanford Genome Technology Center, Genophen has developed a software system dubbed ‘the Genophen platform’ that uses a series of proprietary algorithms to assess patients’ risk of developing complex or multi-factorial diseases such as type II diabetes based on genetic, clinical, environmental, and behavioral information. The platform then provides personalized recommendations to help patients minimize their risk. The platform also prioritizes factors that increase patients’ risk based on their health profiles, and calculates how lifestyle changes could help reduce risk.

Genophen plans to launch its platform publicly in a few weeks, and it will include new features such as a new user interface, Fakhrai-Rad said. He added that in the last year his company has been putting the platform through its paces with a select group of physicians and patients via a pilot project and a currently ongoing beta test program.

The company has also partnered with Illumina’s CLIA laboratory to handle the whole-genome sequencing aspect of its business, Fakhrai-Rad said. Also, it is finalizing arrangements with a second CLIA lab that will offer genotyping services, which are less comprehensive than NGS but much cheaper, Fakhrai-Rad said.

In addition, Fakhrai-Rad stressed that the company will not offer a direct-to-consumer service, but will work in concert with physicians and genetic counselors who will be responsible for discussing a recommended course of action with patients and helping them make decisions about next steps.

For NextBio, the partnership with Genophen reflects a growing demand for its tools from healthcare providers who are looking to make it easier to use whole-genome and targeted sequencing data, NextBio CEO Saeid Akhtari told BioInform.

Historically, the company’s products have been patronized by customers in the pharmaceutical and biotechnology industries involved in drug research and development. However, since the launch of NextBio Clinical last April (BI 4/27/2012), it has begun to receive business from clients in the clinical market including cancer centers, hospitals, and diagnostic companies, Akhtari said.

For instance, last June the company announced that the Cancer Care Institute had licensed its product portfolio — which also includes the NextBio Research software — to analyze oncology patient data for research studies and to select appropriate treatments for patients based on their molecular profiles (BI 6/29/2012).

Earlier this year, Emory University’s Winship Cancer Institute and the Aflac Cancer Center of Children’s Healthcare of Atlanta tapped NextBio Clinical to support their partnership, which is focused on identifying biomarkers that can predict brain cancer metastasis in children in order to help clinicians determine which patients should receive radiation therapy (BI 1/25/2013).

And NextBio expects that the demand for its clinical software to continue to grow and even surpass demand from the pharma/biotech market over the next few years as more clinicians and patients continue to avail themselves of sequencing and molecular profiling technologies, Akhtari said.

The software is also holding its own, Akhtari said, against competing products such as KnomeClinic, a software suite launched by Knome for interpreting and annotating human genomes(BI 6/15/2012).

NextBio believes customers prefer its offering, according to Akhtari, because it provides access to analytic capabilities on private cloud infrastructure so that customers don’t have to purchase their own hardware; offers comprehensive curated content; and comes with an adaptive learning knowledgebase that uses newly incorporated information from patients to improve correlations between variants and disease. The company also updates its software and database content regularly in response to customers’ requests, he said.

Akhtari said that NextBio has potential deals currently going through an “approval process” with other companies besides Genophen, but declined to disclose who those new clients are.

Source: Genophen

New Fnding Increases Chances of Rapid Detection and Targeted Treatment

Men with a faulty gene known to increase the risk of breast cancer in women are four times more likely to develop prostate cancer, important new research published in the British Journal of Cancer shows.

Alzheimer’s Association Awards Largest Ever Research Grant to DIAN for Innovative Therapy Trials

The Alzheimer’s Association announced recently the awarding of its largest ever research grant – nearly $4.2 million over four years – to the Dominantly Inherited Alzheimer’s Network–Therapeutic Trials Unit (DIAN-TTU), based at Washington University School of Medicine in St. Louis, to enable the program to move forward more quickly with innovative drug and biomarker trials in people with genetically-based, young-onset Alzheimer’s disease.