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The New York Times, March 11, 2009, by Roni Caryn Rabin — Only about one-quarter of invasive ovarian cancers are detected in the early stages, when the disease is most treatable. Now, preliminary results from a large, continuing trial indicate that postmenopausal women who are screened for ovarian cancer either by transvaginal ultrasound scan or by a blood test followed by a scan are more likely to have their cancers detected at early stages, with almost half the cancers picked up before they had spread beyond the pelvis.

While the results suggest that widespread screening for ovarian cancer may be feasible, long a point of scientific controversy, the researchers warned that the benefits were still far from clear. Many of the women in the trial had false positive results on screening tests that led to unnecessary surgeries and complications, especially among those who had ultrasound scans alone. And there is still no evidence that screening reduces the death rate from ovarian cancer, the researchers said.

Interim results from the initial screening tests of some 100,000 British women were published online Tuesday in The Lancet Oncology. The trial uses a sophisticated research algorithm to interpret the results of a controversial blood test for the CA125 tumor marker, repeating the tests at specified intervals and following up with scans when indicated. The study is expected to continue through at least 2014.

“We have now demonstrated we can pick up the vast majority of women with ovarian cancer earlier than they would have otherwise been detected and before they have symptoms,” said Dr. Ian Jacobs, director of the Institute for Women’s Health at University College London, and director of the trial, “and that a good proportion of those women have earlier stage disease than we would normally expect them to have.”

But, Dr. Jacobs cautioned that “women thinking of having this must understand and realize that there’s a possibility it will do more harm than good.”

“We have reason to think it will save lives,” he added, “and then the question is, will it save enough lives to balance out the harm it does?”

The clinical trial includes some 202,638 British women ages 50 to 74 who were recruited from 2001 to 2005. About half were randomly assigned to a group that received no screening for ovarian cancer, while the rest were randomly assigned to receive annual screenings via transvaginal ultrasound scans or blood tests for the CA125 tumor marker followed by an ultrasound when indicated.

Some 58 invasive cancers were detected at first screening, and 28 of them, or 48 percent, were in the early stages, the study reported. There were no significant differences between the two screening methods, though the rate of unnecessary surgery was much higher among women screened by ultrasound alone.

Robert Smith, director of cancer screening for the American Cancer Society, said that while it was important to run large clinical trials, the preliminary results must be interpreted with caution. “We’re not even remotely close to knowing how to screen women of average risk with these tests, or even if we should,” he said.

Medical groups have long cautioned against using the results of a single blood test as a basis for further intervention.

Ovarian cancer, which is usually asymptomatic in its early stages, strikes 21,650 women annually in the United States, killing 15,520 a year.

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Screening Methods for Ovarian Cancer Under Study

Tentative Results Show a 20 Percent Increase in Survival Rates

March 11, 2009, by Gary Davis — Ovarian Cancer has long been a killer of women. Ovarian Cancer strikes 21,650 women per year killing 15,520 or nearly 72 percent. There is some hope that the numbers may be changing.

Roni Caryn Rabin reports in her article in The New York Times, “Screening Can Detect Early Ovarian Cancer,” doctors have found a screening test for postmenopausal women as

a result of ongoing studies.

This screening may be as a result of a blood test or a transvaginal ultrasound scan.

The major problem with ovarian cancer is that it has no early symptoms. Usually by the time it is discovered it is too late because it has already left the pelvis and spread to other parts of the body.

Ovarian Cancer is cancer that starts in the ovaries. Ovaries are reproductive glands found only in women that produce eggs or “ova” for reproduction. Ovarian Cancer is a “catch-all” phrase for different types of cancer cells that begin and grow on the ovaries. Even the benign cells must usually be dealt with.

However, there is some disagreement as to the effectiveness of the screening. In fact, only time will tell if the screening saves enough lives to be valuable.

The screening for the ovarian cancer consists of either a blood test or the transvaginal ultrasound scan.

Women between the ages of 50 and 74 were recruited for the British study that ended up with over 200,000 women.

Roughly half of the women were not screened. Their percentages remained consistent with pre-study women.

Of the women screened, 58 yielded positive results of ovarian cancer, however, 48 percent of the cancers were caught before they had a chance to spread.

The problem with the screening methodology at this point, is that there have been false positives so some surgery has been unnecessary.

It is going to take much longer to be able to follow the women and assess whether or not the “cure” is as bad as the illness.

When my wife and I were trying to conceive it was found that she had scarring on her ovaries preventing conception. At that time the doctors told us that the ovaries had to be treated with the scar tissue removed so that there would be no chance of ovarian cancer.

GoogleNews.com, March 11, 2009, by Maria Cheng — Doctors screening women for ovarian cancer were able to pick up the disease about two years earlier than normal, according to a British study published Wednesday.

Scientists have long searched for a way to identify ovarian cancer early, which kills nearly 100,000 women worldwide every year. If it is found early, nearly 90 percent of women survive.

However, most women are currently only diagnosed with the disease after it has spread, when there is only a maximum 30 percent chance of survival.

In the British study, doctors enrolled approximately 200,000 post-menopausal women aged 50 to 74 across the United Kingdom from 2001 to 2005. About 100,000 of those women received no screening tests.

The remaining half were split into two groups. Roughly 50,000 were screened with a blood test. If the blood test results suggested an abnormality, they then had an ultrasound. The rest of the women, nearly 50,000, received an ultrasound only.

In the women who had a blood test first, researchers found 38 who had cancer. In those who only had an ultrasound, there were 32 cancer cases. Using the blood test method, ovarian cancer was picked up 89 percent of the time. With the ultrasound, the rate was about 75 percent.

In these preliminary results, doctors found nearly half of the cancers detected were at an early stage. Normally, doctors would only catch about 15 percent of early ovarian cancer patients.

The study was published online Wednesday in the medical journal, Lancet Oncology.

“I’m cautiously optimistic,” said Robert Smith, director of cancer screening at the American Cancer Society. Smith was not connected to the study.

“This may make a difference to saving lives, but we don’t know that right now,” he said. Smith said the tumors detected in screening are sometimes not the ones that kill.

To know if catching ovarian cancer early saves lives, researchers must wait until the study finishes in 2014 to look at all the data. The study was mainly paid for by Britain’s Medical Research Council, Cancer Research UK and the Department of Health.

“Picking up cancer early is a prerequisite to saving lives,” said Ian Jacobs, one of the study’s authors and dean of health sciences research and director of the Institute for Women’s Health at University College London. “But the question is, is this early enough?”

Experts will also have to weigh the tests’ benefits against its costs. “It’s a big and expensive jump to decide that (national) screening programs might be beneficial,” Smith said.

With any screening test, authorities must determine whether the tests save enough lives to merit the financial and other costs, like patients who will have unnecessary surgeries or psychological distress.

Several companies in the United States are seeking approval from the Food and Drug Administration to sell their tests.

On the Net:

http://www.lancet.com

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March 11, 2009 — The pharmaceutical industry and regulators are each adjusting well to the dawning of personalized medicine, said Lawrence Lesko, PhD, FCP, director of clinical pharmacology and biotherapeutics, U.S. Food and Drug Administration (FDA), recently at the University of Maryland School (Baltimore) of Pharmacy.

By 2019, a typical pharmacy, he said, will display extensive racks of self-testing kits for the risks of gene-associated diseases and a counseling center along side the prescription counter, where the pharmacist will help patients manage drugs designed for their personal genetic makeup.

Such changes will be the inevitable fruits of personalized medicine now taking root, Lesko said, adding that “precision medicine” may have been a better popular name for personalized medicine.

Lesko delivered the annual Andrew G. DuMez Memorial Lecture in honor of the former and pioneering dean of the School, who served the University from 1926-1948, and was a recipient of the highest national pharmacy award, the Remington Medal.

Lesko “is one of the leading thinkers in the area of pharmacology,” says Natalie D. Eddington, PhD, the current dean of the School, which is part of the University of Maryland, Baltimore.

“For precision medicine, the disease must be diagnosed to the gene,” said Lesko, who emphasized that vast amounts of data generated by human genome research in recent years creates an opportunity for drug makers to better target medicines to smaller populations of patients.

But at the same time, the challenge for drug makers is like turning a large field of long-range radar antennae inward into the body, he said. “Who is going to interpret the data? Who will explain that information to the patients? Pharmacists are the logical answer. Precision medicine will need a professional, nonphysician go between.”

Except for lacking a strong business economy for personalized medicine right now, the leading factor holding it back is lack of education, he said.

“We have a public health crisis in this country. Drugs are intended to treat symptoms not diseases.” Instead, “new [personalized] drugs will now be developed by pathways, by going after the biochemical actions set off by genes. Cancer gets it,” added Lesko, referring to new drug discovery and development trends in cancer research that work to find genetic keys for fighting different kinds of cancers.

To ease the pharmaceutical industry into personalized medicine, “centers of pharmacy practice in precision medicine will evolve just like the pharmacy industry has done for all such major changes,” he said.

From the government’s standpoint, Lesko said, “It didn’t take a lot of pushing to get the pharmaceutical industry interested in personalized medicine. New drugs cost drug makers more than an average of $1 billion to market.”

Lesko said pharmacists will not likely be very challenged by the emergence of personalized medicine. But they must first overcome three “limiting factors”: the time constraints of current pharmacy practices; the cost of continuing education; and the evaluation of current interest in taking personalized medicine forward.

For the drug makers, “We need to integrate genomic biomarkers into all phases of drug development,” he said. And for the FDA, “First, we need to set up public-private partnerships to qualify predictive biomarkers” in human cells for disease-fighting drugs.”

Lesko said a current example of a gene-specific drug is Warfarin. The effectiveness of the widely prescribed anticoagulant is variable depending on whether patients have a couple of key genes. The FDA has labeled at least 10 precision medical drugs so far that can be considered personalized medicines, he said.

The FDA has advanced three ideas for the emergence of personalized medicine, said Lesko. It created a “safe harbor” for industry to submit exploratory genomic data. It has a genomic consulting service. And the agency has a center to relabel previously approved drugs with new pharmacological information.

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W. Gregory Feero, MD, PhD

March 11, 2009

The coming year promises to usher in important reforms to the delivery of healthcare in the United States. Rising costs, questions about health care quality, and a business community rendered uncompetitive at least in part by the high cost of employee benefits have aligned strange bedfellows with significant political resources to affect change. The population at large seems ready for reform. Prevention, personalized medicine, and the medical home have become societal buzzwords, with much debate regarding the merits of each concept. The medical home model seems to be growing in currency among multiple segments of the health care ecosystem and has been endorsed by several influential health care provider groups as an essential part of any reform package. Though the exact definition of a medical home is slippery—one is reminded of the parable about the blind men and the elephant—one can make a strong argument that genomic information should have a room reserved in any model of a medical home that gains acceptance.

Tremendous progress has been made over the past 2 years in understanding the genomic underpinnings of many of the disorders most costly to our society. At the same time, the cost of obtaining genomic information has plummeted. Currently, an individual can obtain a “genome-wide scan” for less than $500; such scans contain more than 500,000 bits of information from the genome with potential relevance to health and disease. As of the end of 2008, full genome sequencing costs have decreased more than 10,000- fold from the costs of only 8 years ago—a rate of decline exceeding that of Moore’s law for decreasing cost of semiconductors in the computer industry. There is no evidence that the rate of decline is diminishing—many feel that complete genome sequencing will be available for a price comparable to that of a CT scan within the next 5 to 10 years. Though the rate of accumulation of data is currently outstripping our knowledge of what to do with it, this will not remain the case for long; and failure to develop health care systems that are capable of dealing with genomic information now will do future generations a disservice.

Consider four aspects of care delivery that might logically be part of an individual’s medical home and may potentially be greatly affected by the availability of low-cost, full-genome sequence information: 1) newborn screening; 2) pharmacotherapy; 3) reproductive counseling; and 4) disease risk management.

First, newborn screening panels are the earliest “genetic test” most people encounter. Currently most states test newborns for more than 29 disorders using biochemical measurements, some with very low positive predictive values. It seems likely that many of these tests could be enhanced by having full genome sequence information available from an early age either to replace the biochemical screen or to aid in the interpretations of ambiguous results.

Second, the number of medications for which pharmacogenetic testing is potentially helpful is growing rapidly— and for a handful such testing is imperative. The availability of a repository of genomic sequence data in the context of a medical home seems likely to become a means to economically select the right drug at the right dose for the patient in question.

Third, numerous guidelines currently suggest that patients considering having children be offered the option of genetic testing for carrier status of a variety of conditions with implications for their potential offspring. Patients choosing to access such genomic sequence information in their medical home could do so without need of redundant testing.

Finally, a long and growing list of known genomic variants contribute to a person’s risk of developing common complex conditions like diabetes, heart disease, and cancer. Many of these variants are already being incorporated in disease risk assessment algorithms, and at least some are likely to prove to be helpful in improving both screening and prevention efforts. The availability of full genome sequence information in the context of the medical home could allow patients to access relevant genetic risk information of their choosing at the most appropriate point in life.

The above examples also illustrate that achieving the maximum potential of a genome-enabled (or, in fact, any) medical home will require continued progress in another major technological area—health information technology. One major issue that needs immediate attention, regardless of the ultimate fate of the medical home model, is that genomic data lack interoperability between the majority of electronic medical record systems. The Personalized Health Care Workgroup of the American Health Information Community initiated by former US Department of Health and Human Services Secretary Michael Leavitt has made a start towards addressing this point over the past several years. Early indications are that the Obama administration views both personalized medicine and the electronic medical record as important to the nation’s health, but it is too early to know what initiatives may be put forward in these areas.

A somewhat more pedantic but potentially very costly problem is that billions of bits of genomic data on millions of individuals will overwhelm the storage capacity of current health information technology systems. In the wash of genomic data, information security will be another critical consideration.

Physician assistants are well positioned to be co-architects of any emerging health care reform. The American Academy of Physician Assistants supports the idea of the patientcentered medical home. For the upcoming 111th Congress, the AAPA has made the medical home concept, and clear delineation of the PA role within it, part of their agenda (see www.aapa.org/gandp/pdf/AAPA_HC_Discussion%20_Ltr_to_TDaschle_ 1208.pdf for more information).

As evidenced by this Genetics in Medicine column and numerous other educational activities, the PA community has also been a leader in adopting and enacting competencies for genetics and genomics education for its members. Continued vision and leadership by PAs will help to ensure that the genome has a home in the future of medicine. JAAPA

Michael A. Rackover, PA-C, MS; Constance Goldgar, MS, PA-C, department editors

Gregory Feero is a family physician and Chief, Genomic Healthcare Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland. He has indicated no relationships to disclose relating to this article.

From the March 2009 Issue of JAAPA

By Michael A. Rackover, PA-C, MS; Constance Goldgar, MS, PA-C

In a paper published in the [October 23, 2008] issue of the journal Nature, the Tumor Sequencing Project (TSP) consortium identified 26 genes that are frequently mutated in lung adenocarcinoma—an achievement that more than doubles the number of genes known to be associated with this deadly disease. But this pioneering effort involved far more than just tallying up genes. Using a systematic, multidisciplinary approach, the TSP team also detailed key pathways involved in the disease and described patterns of genetic mutations among different subgroups of lung cancer patients, including smokers and never-smokers.1

This recent announcement of an advance in our understanding of lung cancer is only one example of what is becoming a regular series of announcements of advances in our understanding of genetic contributions to common disease. Since 2005, more than 190 genome-wide association studies (GWAS) have identified robust associations with genetic variants for nearly 70 common, complex diseases and traits, including age related macular degeneration, QT interval prolongation, inflammatory bowel disease, type 2 diabetes, Crohn’s disease, and obesity. We live in exciting times. GWAS and other technologies will promote better diagnosis, improved determination of risk, and more individualized treatment.

This article is the first in a new department in JAAPA that will demonstrate how genetics is becoming the fundamental science for all health care providers and how it has—or soon will— influence your clinical practice as a PA. One of our objectives is to show the clinical relevance of genetics to different disciplines within PA practices. Another is to present current practical applications of genetics, while reinforcing underlying genetic concepts and principles that can be applied more broadly. We hope to provide articles that deliver a snapshot of how genetics and genomics are changing and will continue to change our understanding of the natural science of disease and health.

In addition, we hope the column can serve as a forum for the following:

• Perspectives from experts in genetics/ genomics that allow us to update our clinical toolbox for best practice

• Reviews of current and newly introduced genetics resources for clinicians and practice tools to support critical analysis of genetic literature

• Discussions of clinical genetics concepts: technological advances, genetic testing available to clinicians, important aspects of counseling patients about genetic information, ELSI (ethical, legal, and social implications) issues, and more

• Ethical, historical, and philosophical perspectives on common topics within genetics

• Reports from PA genetic experts who interface with policy groups, national organizations, and patients to help inform PAs at large of issues that will affect their clinical practice.

This first article describes some of the activities PAs are working on in the genetics community.

Genomics versus genetics

According to the World Health Organization, “the main difference between genomics and genetics is that genetics scrutinizes the functioning and composition of the single gene, whereas genomics addresses all genes and their interrelationships in order to identify their combined influence on the growth and development of the organism.”1 In clinical practice, genomics is the recognition of the value that genetic information brings to promoting health as well as to diagnosing, treating, predicting, and preventing all diseases, not only genetic diseases.

1. WHO definitions of genetics and genomics. World Health Organization Web site. http://www.who.int/genomics/ geneticsVSgenomics/en/. Accessed December 11, 2008.

Michael Rackover, one of the department editors, is serving his second term on the Board of Directors of the National Coalition for Health Professional Education in Genetics (NCHPEG) and also is a liaison from AAPA to the NCHPEG. He completed a 4-month sabbatical at the National Human Genome Research Institute (NHGRI) at the National Institutes of Health in 2006. Rackover organized a 2-day meeting in March 2007 attended by the executives of the four PA organizations; the acting surgeon general, Rear Admiral Kenneth Moritsugu, MD; and Dr. Francis Collins, along with his staff at the NHGRI. The purpose of the meeting was to develop an outline for how PAs can use current and anticipated genetics knowledge in the clinical setting. Rackover won the 2008 Physician Assistant Education Association (PAEA) Outstanding Service Award in part for his work in helping PAs to learn about genomics.

Constance Goldgar, the co-department editor, serves as the PAEA represen tative to NCHPEG. She (as lead author) and an energetic group of PAs and genetics experts developed and launched the CME Web site Genetics in the Physician Assistant’s Practice (http://pa.nchpeg.org). This past year, with Michael Rackover and others, she has worked to establish guidelines for PA clinical competencies in genetics/ genomics2 as well as recommendations for a medical genetics curriculum specifically for PAs.3 Currently, Goldgar is working with the interprofessional NCHPEG GeneFacts group to develop point-of-care genetics tools for clinicians.

Karen Clarke, a PA with a master’s degree and board certification in genetic counseling, has contributed to graduate and professional PA education in genetics over the past 2 years. Clarke recently volunteered to represent AAPA for the working group Evaluation of Genomic Applications in Practice and Prevention (EGAPP). The EGAPP pilot initiative was launched in 2004 by the CDC’s National Office of Public Health Genomics to establish a systematic, evidence-based process to evaluate genetic tests and other applications of genomic technology as they transition from research to clinical and public health practice. This independent, nonfederal expert panel, the EGAPP Working Group, has been formed to provide recommendations based on the analytic validity, clinical validity, and clinical utility of genetic tests used in specific clinical scenarios. For more information about EGAPP, please visit www.egappreviews.org/about.htm.

We know that other PAs are working in the genetics/genomics arena, and we extend an invitation to you to help us develop a robust cadre of expert PAs who can share perspectives, knowledge, and questions as we all grapple with genetic issues and the future of medicine. Write to jaapa@haymarketmedia.com with your thoughts and ideas.

Alan E. Guttmacher, MD, acting director of the NHGRI is delighted that JAAPA will be publishing this series of articles about genomics and its increasingly important medical applications. Genomics will soon change the way we practice medicine every day. For this transformation in clinical care to happen in a timely and effective manner, providers—and patients—will have to increase their genetics literacy. This series is an important step towards that goal. Dr. Guttmacher applauds the PA profession for being among the first to take on the challenge of applying the incredibly powerful new tool of genomics to patient care.

Please look forward to reading our forum bimonthly. JAAPA

REFERENCES

1. Large-scale genetic study sheds new light on lung cancer, opens door to individualized treatment strategies. NIH News. http://www.genome.gov/27528559. October 23, 2008. Accessed December 11, 2008.

2. Rackover M, Goldgar C, Wolpert C, et al. Establishing essential physician assistant clinical competencies guidelines for genetics and genomics. Journal of Physician Assistant Education. 2007;18(2):48-49.

3. Goldgar C, Rackover M. Recommendations for a physician assistant medical genetics curriculum. Journal of Physician Assistant Education. 2008;19(2):30-36.

Michael Rackover is program director and associate professor, Physician Assistant Program, Philadelphia University, Philadelphia, Pennsylvania. Constance Goldgar is associate director and assistant professor at the University of Utah Physician Assistant Program, Salt Lake City. The authors have no relationships to disclose relating to the content of this article.