The Cancer Biomarker Conundrum: Too Many False Discoveries

The boom in cancer [including ovarian] biomarker investments over the past 25 years has not translated into major clinical success. The reasons for biomarker failures include problems with study design and interpretation, as well as statistical deficiencies, according to an article published online August 12 in The Journal of the National Cancer Institute.

The boom in cancer [including ovarian] biomarker investments over the past 25 years has not translated into major clinical success. The reasons for biomarker failures include problems with study design and interpretation, as well as statistical deficiencies, according to an article published online August 12 in The Journal of the National Cancer Institute.

The National Institutes of Health defines a biomarker as “a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” In the past decade, there have been numerous biomarker discoveries, but most initially promising biomarkers have not been validated for clinical use.

Eleftherios P. Diamandis, M.D., Ph.D., Head, Section of Clinical Biochemistry, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada

To understand why so-called biomarker “breakthroughs” have not made it to the clinic, Eleftherios P. Diamandis, M.D., Ph.D., professor of pathology and laboratory medicine at Mount Sinai Hospital in Toronto and associate scientist at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, reviewed some biomarkers initially hailed as breakthroughs and their subsequent failings.

Diamandis first describes the requirements for biomarkers to be approved for clinical use: A biomarker must be released into circulation in easily detectable amounts by a small asymptomatic tumor or its micro-environment; and it should preferably be specific for the tissue of origin. Also, if the biomarker is affected by a non-cancer disease, its utility for cancer detection may be compromised. For example, the prostate-specific antigen (PSA) biomarker, which is used to detect prostate cancer, is also elevated in benign prostatic hyperplasia.

Diamandis looks at seven biomarkers that have emerged in the past 25 years, all of which were considered promising when they were first described. These include nuclear magnetic resonance of serum for cancer diagnosis; lysophosphatidic acid for ovarian cancer; four– and six-parameter diagnostic panels for ovarian cancer; osteopontin for ovarian cancer; early prostate cancer antigen-2 (EPCA-2) for prostate cancer detection; proteomic profiling of serum by mass spectrometry for ovarian cancer diagnosis; and peptidomic patterns for cancer diagnosis. Problems ranged from inappropriate statistical analysis to biases in case patient and control subject selection. For example, the problems with EPCA-2 included reporting values that were beyond the detection limit of the assay and using inappropriate reagents to test EPCA-2, such as solid surfaces coated with undiluted serum.

Diamandis concludes that “problems with pre-analytical, analytical, and post-analytical study design could lead to the generation of data that could be highly misleading.”

Sources:

The Cancer Biomarker Conundrum: Too Many False Discoveries, Journal of the National Cancer Institute Advance Access,  published on August 12, 2010, DOI 10.1093/jnci/djq335.

Eleftherios P. Diamandis. Cancer Biomarkers: Can We Turn Recent Failures into Success? Commentary, Journal of the National Cancer Institute Advance Access published on August 12, 2010, DOI 10.1093/jnci/djq306.

Georgia Tech’s Ovarian Cancer Early Detection Blood Test Exhibits High Accuracy in Small Study; Larger Study Planned

Scientists at the Georgia Institute of Technology have attained very promising results on their initial investigations of a new test for ovarian cancer. Using a new technique involving mass spectrometry of a single drop of blood serum, the test correctly identified women with ovarian cancer in 100 percent of the 94 patients tested. Because of the extremely low prevalence of ovarian cancer in the general population (∼0.04%), extensive prospective testing will be required to evaluate the test’s potential utility in general screening applications.

Scientists at the Georgia Institute of Technology have attained very promising results on their initial investigations of a new test for ovarian cancer. Using a new technique involving mass spectrometry of a single drop of blood serum, the test correctly identified women with ovarian cancer in 100 percent of the 94 patients tested. The results can be found online in the journal Cancer Epidemiology, Biomarkers, & Prevention Research.

John McDonald, Ph.D., Professor, Associate Dean for Biology Program Development, Georgia Institute of Technology; Chief Science Officer, Ovarian Cancer Institute

Facundo Fernandez, Ph.D., Associate Professor, School of Chemistry & Biochemistry, Georgia Institute of Technology

“Because ovarian cancer is a disease of relatively low prevalence, it’s essential that tests for it be extremely accurate. We believe we may have developed such a test,” said John McDonald, chief research scientist at the Ovarian Cancer Institute (Atlanta) and professor of biology at Georgia Tech.

The measurement step in the test, developed by the research group of Facundo Fernandez, associate professor in the School of Chemistry and Biochemistry at Tech, uses a single drop of blood serum, which is vaporized by hot helium plasma. As the molecules from the serum become electrically charged, a mass spectrometer is used to measure their relative abundance. The test looks at the small molecules involved in metabolism that are in the serum, known as metabolites. Machine learning techniques developed by Alex Gray, assistant professor in the College of Computing and the Center for the Study of Systems Biology, were then used to sort the sets of metabolites that were found in cancerous plasma from the ones found in healthy samples. Then, McDonald’s lab mapped the results between the metabolites found in both sets of tissue to discover the biological meaning of these metabolic changes.

The assay did extremely well in initial tests involving 94 subjects. In addition to being able to generate results using only a drop of blood serum, the test proved to be 100 percent accurate in distinguishing sera from women with ovarian cancer from normal controls. In addition it registered neither a single false positive nor a false negative

The group is currently in the midst of conducting the next set of assays, this time with 500 patients.

“The caveat is we don’t currently have 500 patients with the same type of ovarian cancer, so we’re going to look at other types of ovarian cancer,” said Fernandez. “It’s possible that there are also signatures for other cancers, not just ovarian, so we’re also going to be using the same approach to look at other types of cancers. We’ll be working with collaborators in Atlanta and elsewhere.”

In addition to having a relatively low prevalence, ovarian cancer is also asymptomatic in the early stages. Therefore, if further testing confirms the ability to accurately detect ovarian cancer by analyzing metabolites in the serum of women, doctors will be able detect the disease early and save many lives.

Libby’s H*O*P*E*™ Comment:

Alex Gray, Ph.D., Assistant Professor, College of Computing & Center for the Study of Systems Biology, Georgia Institute of Technology

This study involved testing the metabolite levels in blood sera from 44 women diagnosed with serous papillary ovarian cancer (stages I-IV) and 50 healthy women or women with benign conditions.  The assay distinguished between the cancer and control groups with an unprecedented 99% to 100% accuracy. The method possesses significant clinical potential as a cancer diagnostic tool.  Because of the extremely low prevalence of ovarian cancer in the general population (∼0.04%), extensive prospective testing will be required to evaluate the test’s potential utility in general screening applications.

Sources:

Initial Trials On New Ovarain Cancer Tests Exhibit Extremely High Accuracy, News Release, Georgia Institute of Technology, August 11, 2010.

Zhou M,Guan W, Walker LD, et. al. Rapid Mass Spectrometric Metabolic Profiling of Blood Sera Detects Ovarian Cancer with High Accuracy. Cancer Epidemiol Biomarkers Prev 1055-9965.EPI-10-0126; Published OnlineFirst August 10, 2010; doi:10.1158/1055-9965.EPI-10-0126

On the Path to Early Detection: Fox Chase & Sloan-Kettering Researchers Identify Early Ovarian Cancers

Researchers at the Fox Chase Cancer Center and the Memorial Sloan-Kettering Cancer Center discover early tumors and precancerous lesions in cysts that fold into the ovary from its surface, called inclusion cysts. “This is the first study giving very strong evidence that a substantial number of ovarian cancers arise in inclusion cysts and that there is indeed a precursor lesion that you can see, put your hands on, and give a name to,” says Jeff Boyd, PhD, Chief Scientific Officer at Fox Chase and lead author on the study …

Ovarian cancer kills nearly 15,000 women in the United States each year, and fewer than half of the women diagnosed with the disease survive five years. A screening test that detects ovarian cancer early, when it is still treatable, would likely reduce the high mortality, yet scientists have not known where the tumors originate or what they look like. Now, researchers at Fox Chase Cancer Center think they have answered both questions. The study, published on April 26th in PLoS ONE, reports that they have uncovered early tumors and precancerous lesions in cysts that fold into the ovary from its surface, called inclusion cysts.

Jeff Boyd, Ph.D., Professor, Chief Scientific Officer & Senior Vice President, The Robert C. Young, MD, Chair in Cancer Research, Fox Chase Cancer Center

“This is the first study giving very strong evidence that a substantial number of ovarian cancers arise in inclusion cysts and that there is indeed a precursor lesion that you can see, put your hands on, and give a name to,” says Jeff Boyd, PhD, Chief Scientific Officer at Fox Chase and lead author on the study, which also involved colleagues at the Memorial Sloan-Kettering Cancer Center. “Ovarian cancer most of the time seems to arise in simple inclusion cysts of the ovary, as opposed to the surface epithelium.”

Clinicians and researchers have been looking for early ovarian tumors and the precancerous lesions from which they develop for years without success. In this study, Boyd and colleagues used a combination of traditional microscopy and molecular approaches to reveal the early cancers.

“Previous studies only looked at this at the morphologic level, looking at a piece of tissue under a microscope,” Boyd says. “We did that but we also dissected away cells from normal ovaries and early stage cancers, and did genetic analyses. We showed that you could follow progression from normal cells to the precursor lesion, which we call dysplasia, to the actual cancer, and see them adjacent to one another within an inclusion cyst.”

To learn where and how the tumors arise, the team examined ovaries removed from women with BRCA mutations, who have a 40% lifetime risk of developing ovarian cancer, and from women without known genetic risk factors. In both groups, they found that gene expression patterns were dramatically different in cells in the inclusion cysts compared to the normal surface epithelium cells, including increased expression of genes that control cell division and chromosome movement.

Moreover, when they used a technique called FISH (fluorescence in situ hybridization), which can be used to identify individual chromosomes in cells, they saw that cells from very early tumors and precursor lesions frequently carried extra chromosomes. In fact, the team found that 9% of the normal cells isolated from the cysts had extra chromosomes, even though the tissue appeared completely benign under the microscope. By contrast, virtually none of the cells isolated from the surface of the ovary, which was previously thought to be the site of early ovarian cancers, carried extra chromosomes.

With these new data on the origin of ovarian cancer in hand, Boyd and others can now start to develop screening tests, perhaps based on molecular imaging, that could be used to detect early ovarian cancers in asymptomatic women.

Co-authors on the study include Bhavana Pothuri, Mario M. Leitao, Douglas A. Levine, Agnès Viale, Adam B. Olshen, Crispinita Arroyo, Faina Bogomolniy, Narciso Olvera, Oscar Lin, Robert A. Soslow, Mark E. Robson, Kenneth Offit, and Richard R. Barakat of Memorial Sloan-Kettering Cancer Center.

About the Fox Chase Cancer Center

Fox Chase Cancer Center is one of the leading cancer research and treatments centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet status for excellence three consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. For more information, call 1-888-FOX-CHASE or 1-888-369-2427.

Sources:

Abbott Labs Seeks FDA 510(k) Clearance For New Automated Ovarian Cancer Detection Test

A new diagnostic tool physicians can use to monitor patients for the most common form of ovarian cancer may soon be available in the United States.

Abbott Laboratories’ ARCHITECT HE4 assay uses a simple blood test to help in monitoring for the recurrence or progression of epithelial ovarian cancer. If approved by the FDA, this important immunoassay would be the first automated HE4 test available in the United States.

A new diagnostic tool physicians can use to monitor patients for the most common form of ovarian cancer may soon be available in the United States.  Abbott Laboratories’ (Abbott’s) ARCHITECT [Human Epididymal Protein 4] HE4 assay uses a simple blood test to help in monitoring for the recurrence or progression of epithelial ovarian cancer. If approved by the U.S. Food & Drug Administration (FDA), this important immunoassay would be the first automated HE4 test available in the United States.

The 2003 Hellstrom et al. study of known ovarian cancer biomarkers found that HE4, which has been detected in high levels in the blood of some ovarian cancer patients, shows the highest sensitivity and specificity of any other marker and is considered the best single marker for stage 1 of the disease.

According to the American Cancer Society, the five-year survival rate of ovarian cancer patients is 46 percent. However, when the disease is diagnosed and treated earlier, the survival rate increases to 93 percent. Less than 20 percent of all ovarian cancer is found in the early stage.

“The ability to monitor the recurrence or progression of ovarian cancer is a critical part of patient care. The ARCHITECT HE4 assay has the potential to be a powerful tool for both physicians and patients in the management of the disease,” said Michael Warmuth, Senior Vice President, Diagnostics, Abbott.

Abbott partnered with Fujirebio Diagnostics, Inc. in the development of the assay. The ARCHITECT HE4 assay is approved for use in Europe, as well as in other countries in Asia Pacific and Latin America. It is currently an investigational device in the United States.

About ARCHITECT HE4 Assay

The ARCHITECT HE4 assay is designed to be used as an aid in monitoring recurrence or progressive disease in patients with epithelial ovarian cancer, and must be used in conjunction with other clinical data. The ARCHITECT HE4 assay should not be used as a cancer screening test. In addition, certain types of cancer (e.g., mucinous or germ cell tumors) rarely express HE4, and the use of the ARCHITECT HE4 assay is not recommended for monitoring patients with those types of cancer.

About Ovarian Cancer

Ovarian cancer is the leading cause of death from gynecological cancers and the fifth-leading cause of cancer death in women. An estimated one in 71 women will develop ovarian cancer in their lifetimes. Women who are postmenopausal are at the greatest risk for ovarian cancer.

About Abbott Diagnostics

Abbott Diagnostics is a global leader in in vitro diagnostics (IVD) and offers a broad range of innovative instrument systems and tests for hospitals, reference labs, blood banks, physician offices and clinics. With more than 69,000 institutional customers in more than 100 countries, Abbott’s diagnostic products offer customers automation, convenience, cost effectiveness and flexibility. The history of Abbott Diagnostics is filled with examples of first-of-a-kind products and significant technological advancements, including the development of the very first diagnostic test to detect HIV.

About Abbott’s Diagnostics Businesses

Abbott is a global leader in in vitro diagnostics and offers a broad range of innovative instrument systems and tests for hospitals, reference labs, molecular labs, blood banks, physician offices and clinics. With more than 69,000 customers in more than 100 countries, Abbott’s diagnostic products offer customers automation, convenience, bedside testing, cost effectiveness and flexibility. Abbott has helped transform the practice of medical diagnosis from an art to a science through the company’s commitment to improving patient care and lowering costs.

About Abbott

Abbott (NYSE: ABT) is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs more than 72,000 people and markets its products in more than 130 countries.

References:

  • FDA 510(k) Clearances – Overview, Device Approvals & Clearances, Products & Medical Procedures, Medical Devices, U.S. Food & Drug Administration, U.S. Department of Health & Human Services.

Additional Information:

Anderson GL, McIntosh M, Wu L, et. al. Assessing lead time of selected ovarian cancer biomarkers: a nested case-control study. J Natl Cancer Inst. 2010 Jan 6;102(1):26-38. Epub 2009 Dec 30. PubMed PMID: 20042715;PubMed Central PMCID: PMC2802285.

Andersen MR, Goff BA, Lowe KA, et. al. Use of a Symptom Index, CA125, and HE4 to predict ovarian cancer. Gynecol Oncol. 2009 Nov 27. [Epub ahead of print] PubMed PMID: 19945742.

Moore RG, McMeekin DS, Brown AK, et. alA novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass. Gynecol Oncol. 2009 Jan;112(1):40-6. Epub 2008 Oct 12. PubMed PMID: 18851871.

Hellstrom I, Hellstrom KE. SMRP and HE4 as biomarkers for ovarian carcinoma when used alone and in combination with CA125 and/or each other. Adv Exp Med Biol. 2008;622:15-21. Review. PubMed PMID: 18546615.

Havrilesky LJ, Whitehead CM, Rubatt JM, et. al. Evaluation of biomarker panels for early stage ovarian cancer detection and monitoring for disease recurrence. Gynecol Oncol. 2008 Sep;110(3):374-82. Epub 2008 Jun 27. PubMed PMID: 18584856.

Moore RG, Brown AK, Miller MC, et. al. The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol. 2008 Feb;108(2):402-8. Epub 2007 Dec 3. PubMed PMID:  18061248.

Rosen DG, Wang L, Atkinson JN, et. al. Potential markers that complement expression of CA125 in epithelial ovarian cancer. Gynecol Oncol. 2005 Nov;99(2):267-77. Epub 2005 Aug 2.  PubMed PMID: 16061277.

Drapkin R, von Horsten HH, Lin Y, et. al. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res. 2005 Mar 15;65(6):2162-9. PubMed PMID: 15781627.

Elevated Proteins May Warn of Ovarian Cancer, But Sufficient Lead Time & Predictive Value Still Lacking

Fred Hutchinson Cancer Center researchers discovered that concentrations of the serum biomarkers CA125, human epididymis protein 4 (HE4), and mesothelin began to rise 3 years before clinical diagnosis of ovarian cancer, according to a new study published online December 30 in the Journal of the National Cancer Institute. However, the biomarkers became substantially elevated only in the last year prior to diagnosis. … In an accompanying editorial to the study results reported by Anderson et. al., Patricia Hartge, ScD, of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute, applauds the researchers for taking the field one step closer to successful screening study designs by showing that the levels of certain biomarkers do not increase early enough to be used for screening.

Fred Hutchinson Cancer Center researchers discovered that concentrations of the serum biomarkers CA125, human epididymis protein 4 (HE4), and mesothelin began to rise 3 years before clinical diagnosis of ovarian cancer, according to a new study published online December 30 in the Journal of the National Cancer Institute (JNCI). [1] However, the biomarkers became substantially elevated only in the last year prior to diagnosis.

Garnet L. Anderson, Ph.D., Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.

CA125, HE4, mesothelin, B7-H4, decoy receptor 3, and spondin-2 have been identified as potential ovarian cancer serum biomarkers, but their behavior in the prediagnostic period, with the exception of CA125, has not been evaluated.  In the JNCI study, Garnet L. Anderson, Ph.D., of the Division of Public Health Sciences at the Fred Hutchinson Cancer Research Center in Seattle, and colleagues analyzed prediagnostic serum samples and patient data from the Carotene and Retinol Efficacy Trial (CARET), a randomized, double-blind, placebo-controlled chemoprevention trial testing the effects of beta-carotene and retinol on lung cancer incidence among individuals at high risk for lung cancer. Prediagnostic serum samples (taken up to 18 years prior to diagnosis) were obtained for 34 CARET patients with ovarian cancer and 70 matched control CARET subjects. Changes in the levels of these biomarkers prior to ovarian cancer diagnosis were analyzed.

Anderson et. al. discovered that concentrations of CA125, HE4, and mesothelin (but not B7-H4, decoy receptor 3, and spondin-2) began to increase slightly in cancer patients relative to control subjects approximately 3 years before diagnosis, but became substantially elevated within one year prior to diagnosis. Thus, the diagnostic value of these biomarkers is limited because accuracy only increased shortly before diagnosis. “Although these markers are not accurate enough to prompt early intervention in existing screening protocols, the multivariable regression analyses identified modest but statistically significant increases in risk associated with CA125, HE4, and mesothelin, which are consistent with many of the established epidemiological risk factors for ovarian cancer,” say the authors of the study.

“I still think biomarkers may play a role in a cost-effective screening program, although none of these seem accurate enough either alone or together to justify their use in average-risk women,” Anderson told Medscape Oncology. “I do not know of any other currently identified biomarkers that hold more promise than these, but there has been a massive effort over the last few years to identify candidates and not all have been thoroughly vetted,” said Dr. Anderson.

One problem, cites Dr. Anderson, may lie in the approach used in identifying potential ovarian cancer biomarkers. “Most of the discovery work done so far has been conducted in women with advanced-stage disease and compared them to healthy women,” she explained. “If discovery work were done in samples like the ones we used here, representing specimens collected months to years prior to the advanced stage diagnosis, we might have a better chance of finding earlier signals of aggressive disease.”

Another opportunity for improving screening and early diagnosis lies in imaging, she adds. “Currently the most common and only affordable imaging option that could be considered for routine screening is transvaginal ultrasound, but it performs poorly in terms of accurately determining those women [who] have ovarian cancer from those who do not,” said Dr. Anderson. “A substantial improvement in this area would be very exciting.”

Study Limitations Cited By JNCI Editors

The JNCI editors state three limitations that they believe are associated with the study by Anderson et. al. First, the study sample size was small.  Second, all women who participated in CARET had a history of heavy smoking, and therefore, the JNCI editors believe that the blood serum testing results obtained by Anderson et. al. may not apply to other non-smoking groups. Third, the blood collected from women participating in CARET was collected at different times, but only a few samples were collected during the last 2–3 years before ovarian cancer diagnosis.

Designing Ovarian Cancer Early Detection Programs — Accompanying JNCI Editorial

Patricia Hartge, Sc.D. Deputy Director, Epidemiology and Biostatistics Program, Division of Cancer Epidemiology & Genetic, National Cancer Institute

In an accompanying editorial to the study results reported by Anderson et. al., Patricia Hartge, ScD, of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute, applauds the researchers for taking the field one step closer to successful screening study designs by showing that the levels of certain biomarkers do not increase early enough to be used for screening. [2]

Dr. Hartge notes that despite the discovery that CA125 and other serum markers increase before the clinical onset of ovarian cancer, it has been exceedingly difficult to devise a successful ovarian cancer early screening program for asymptomatic women. Nevertheless, Hartge believes that Anderson et al. take a valuable step toward the design of such a successful screening program by demonstrating why screening regimens that are based on markers, or panels of markers, can fail. Specifically, the researchers discovered that blood levels of CA125, HE4, mesothelin, and three other promising markers did not increase early enough in the course of the disease to allow detection in early stages. Dr. Hartge emphasizes that the markers typically rose within one year of the disease symptoms that led to an accurate diagnosis, and therefore, many of the ovarian cancer patients were diagnosed with advanced stage disease.

Hartge further states “[t]hat the results of Anderson et al. are not the last word in serum markers or in combinations of markers.” “Serum markers likely will form a key element in any screening regimen, with the lead time and other parameters of each marker or combination of markers being taken into account. The careful evaluation technique applied in the current study fits into a staged approach necessary for testing performance of early markers of disease.” Hartge adds that “[o]nly the time-consuming, expensive, and demanding randomized clinical trial can reveal whether an early detection program that includes the biomarkers can save lives.”

In support of her position, Dr. Hartge observes that current randomized trials are testing the value of different screening programs that are built on combinations of CA125, ultrasound, and risk factor data (e.g., family history and age). After four rounds of screening 34,261 postmenopausal women for ovarian cancer with both CA125 and ultrasound, University of Alabama at Birmingham School of Medicine investigators of the large U.S. screening trial observed that the predictive value of a positive screen was quite low — approximately 1%. Of the 60 screen-detected cancers, 72% had already advanced to at least stage III. [3] In addition, of every 20 women who underwent surgery after a positive screen, only one women was diagnosed with cancer. Furthermore, in a recent UK trial with a slightly different design, positive predictive values from the first round of screening were higher; 35% in the 50,078 women whose risk was assessed with CA125 and risk factor data, followed by ultrasound only if indicated, and 3% in the 50,639 women screened first with ultrasound. [4] The effects on mortality in both trials remain to be determined.

Confronting The “Daunting Arithmetic” Required To Detect Early Stage Ovarian Cancer

Based upon the foregoing, Dr. Hartge highlights the “daunting arithmetic” required to detect early stage ovarian cancer. In the U.S., Surveillance, Epidemiology and End Results (SEER) data indicates that incidence amounts to 13 cases of ovarian cancer per 100,000 woman per year, referred to by Dr. Hartge as the “proverbial needles in the haystack.” [5] So as not to present a problem without a potential solution, Hartge provides a roadmap to additional factors that may help future researchers develop early screening methods to identify those rare cases of ovarian cancer in the general population.  Notably, SEER data also indicates that incidence of ovarian cancer steadily increases with age from 21 cases per 100,000 women per year within the 50-54 age range to 57 cases per 100,000 women per year within the 80-84 age range. [6] Furthermore, family history, low parity, and more ovulations over a woman’s lifetime predict additional risk, with the strongest but least common predictor being a mutation in the BRCA1 or BRCA2 gene. Thus, the general approach suggested by Hartge focuses on women with higher baseline risks, for whom the predictive value of a positive serum test tends to increase. Dr. Hartge believes that the performance of an overall screening program will improve by targeting higher-risk subgroups of women for screening by combining personal history, genetic abnormality status, and levels of serum markers in one prediction model. With ongoing advances in understanding the origin and causes of ovarian cancer, Hartge states that the risk models that are useful for screening programs should also improve.

Further technology advancements may also improve future ovarian cancer early detection screening models, says Hartege. For example, a screening program that is based on a panel of biomarkers can be improved by developing new medical imaging technology that is more specific than current ultrasound technology.  If better imaging existed, fewer women would undergo surgery following a suspicious biomarker finding.  Similarly, development of less invasive surgery could further reduce harmful side effects.  Although Hartge observes that a highly accurate biomarker(s) or an overall screening program does not yet exist, she also explains that the current study by Anderson et. al., with its sobering implications, brings future researchers closer to understanding the crucial elements in designing an effective early detection program for ovarian cancer.

References:

1/Anderson GL , McIntosh M, Wu L, et. al. Assessing Lead Time of Selected Ovarian Cancer Biomarkers: A Nested Case–Control Study. Journal of the National Cancer Institute Advance Access published on January 6, 2010, DOI 10.1093/jnci/djp438. J. Natl. Cancer Inst. 102: 26-38.

2/Hartge P. Designing Early Detection Programs for Ovarian Cancer. Journal of the National Cancer Institute Advance Access published on January 6, 2010, DOI 10.1093/jnci/djp450. J. Natl. Cancer Inst. 102: 3-4.

3/Partridge E, Kreimer AR, Greenlee RT, et al. Results from four rounds of ovarian cancer screening in a randomized trial. Obstet Gynecol (2009) 113(4):775–782. [PMCID: PMC2728067; PMID: 19305319].

4/Menon U, Gentry-Maharaj A, Hallett R, et al. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol (2009) 10(4):327–340. [PMID: 19282241]

5/ Horner MJ, Ries LAG, Krapcho M, et al, eds. SEER Cancer Stat Fact Sheets (2009) Bethesda, MD: National Cancer Institute. http://seer.cancer.gov/statfacts/html/ovary.html. Accessed December 2, 2009.

6/Horner MJ, Ries LAG, Krapcho M, et. al., eds. SEER Cancer Statistics Review, 1975-2006, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2006, based on November 2008 SEER data submission, posted to the SEER web site, 2009 [See Table 21.6: Incidence & Mortality Rates By Age].

Sources:

Barack Obama Proclaims September 2009 As National Ovarian Cancer Awareness Month

Yesterday, U.S. President Barack Obama designated September 2009 as National Ovarian Cancer Awareness Month.  National Ovarian Cancer Awareness Month helps educate women and men about the importance of knowing the early warning signs and symptoms of the disease, scheduling routine doctor visits, and continuing robust scientific research.

Yesterday, U.S. President Barack Obama designated September 2009 as National Ovarian Cancer Awareness Month.  The official proclamation issued by the White House is set forth below.  National Ovarian Cancer Awareness Month helps educate women and men about the importance of knowing the early warning signs and symptoms, scheduling routine doctor visits, and continuing robust scientific research.

White House SealTHE WHITE HOUSE

Office of the Press Secretary

______________________________________________________________________

For Immediate Release August 31, 2009

NATIONAL OVARIAN CANCER AWARENESS MONTH, 2009

– – – – – – –

BY THE PRESIDENT OF THE UNITED STATES OF AMERICA

A PROCLAMATION

Ovarian cancer remains the leading cause of death from gynecologic cancer among women in the United States. Every year, thousands are diagnosed and go on to fight the disease with grace and dignity. National Ovarian Cancer Awareness Month honors all those affected by this cancer and renews our commitment to fighting an illness that takes the lives of too many in our Nation.

Women are often diagnosed with ovarian cancer when it is already at an advanced stage. This problem can be attributed to a lack of effective early detection technologies and minimal or no specific symptoms associated with the disease. By learning more about risk factors and maintaining regular physician consultations, women have their best chance of early detection of ovarian cancer.

Science continues to expand our knowledge about this illness, promising hope to those who, years ago, would be without it. Through dedicated research, treatment outcomes have improved for many, and we are building a foundation for the development of evidence-based screening, which can help diagnose the disease at the earliest possible stage when the likelihood of cure is high.

This month we recommit to supporting the women who continue to battle valiantly against this malady as well as all families who are affected. National Ovarian Cancer Awareness Month helps educate women and men about the importance of knowing common signs and symptoms, scheduling routine doctor visits, and continuing robust scientific research. As a Nation, we are united in our resolve to reduce incidence and improve the lives of all those affected.

NOW, THEREFORE, I, BARACK OBAMA, President of the United States of America, by virtue of the authority vested in me by the Constitution and laws of the United States, do hereby proclaim September 2009 as National Ovarian Cancer Awareness Month. I encourage citizens, Government agencies, private businesses, nonprofit organizations, and other interested groups to join in activities that will increase awareness of what Americans can do to prevent and control ovarian cancer.

IN WITNESS WHEREOF, I have hereunto set my hand this thirty-first day of August, in the year of our Lord two thousand nine, and of the Independence of the United States of America the two hundred and thirty-fourth.

BARACK OBAMA

Source: NATIONAL OVARIAN CANCER AWARENESS MONTH, 2009, By the President of the United States of America, A Proclamation, Office of the Press Secretary For The President of the United States of America, The White House, August 31, 2009.

UA Research Team Designing Holographic Imaging System For Ovarian Cancer

University of Arizona researchers Jennifer Barton and Ray Kostuk have received a five-year, $2.4 million grant from the National Institutes of Health to build the instrument that they hope will one day be used to monitor women at high risk for ovarian cancer.

Hologram of Human Ovary

Human ovary image captured with the use of the prototype holographic imaging system the team developed. (Photo: Univ. of Arizona News)

Hologram of An Orange

For comparison, an onion is imaged with the use of the prototype system the team developed. (Photo: Univ. of Arizona News)

Two University of Arizona [UA] researchers have formed a research team to design, build and evaluate two versions of an ovarian cancer medical imaging and screening instrument that will use holographic components in a new type of optical microscope.

Raymond Kostuk and Jennifer Barton have secured a five-year, $2.4 million grant from the National Institutes of Health to build the instrument that they hope will one day be used to monitor women at high risk for ovarian cancer. Kostuk is the Kenneth Von Behren Professor of Electrical and Computer Engineering and professor of optical sciences. Barton heads the UA department of biomedical engineering and is assistant director of the BIO5 Institute.

The system is unique in that it will for the first time project multiple spatial images from different depths within a tissue sample and simultaneously provide spectral information from optical markers in order to better identify cancerous cells.

This combined spectral spatial imaging technique shows potential to be much more effective in identifying cancerous tissue sites than by separately using spatial or spectral information.

The grant was issued following the successful two-year development of a prototype system the team built. It tests the validity of using holographic technology for subsurface imaging without having to perform surgery and take tissue samples.

According to the National Institutes of Health, there is, to date, no single effective screening test for ovarian cancer, so ovarian cancer is rarely diagnosed in its early stages. The result is that in more than 50 percent of women with ovarian cancer are diagnosed in the late stages of the disease when the cancer has already advanced.

  • About 76 percent percent of women with ovarian cancer survive one year after diagnosis.
  • About 45 percent live longer than 5 years after diagnosis.

Barton said ovarian cancer provides a compelling case to test holographic imaging and its efficacy in detecting cancers. At the present time the preferred treatment is surgery, which is also often needed to diagnose ovarian cancer. The procedure includes taking tissue samples, which may threaten the woman’s ability to have children in the future.

Jennifer Barton, UA

Jennifer Barton, Professor & Chair, Department of Biomedical Engineering; Assistant Director, BIO5 Institute. (Photo: Univ of Arizona News)

“Ovarian cancer has no symptoms until it is highly advanced making the five-year prognosis extremely poor. Those at high risk – with a family history of ovarian cancer or those who carry genetic mutations in the BRCA1 and BRCA2 genes, which normally help protect against both breast and ovarian cancer – may be counseled to have their ovaries removed through laparoscopic surgery,” Barton said. “Now imagine if you are an 18-year-old woman who has this history – ovaries are an important part of your overall health. They produce hormones you need over and above the notion that you would need your ovaries should you want to have children in the future.”

Thus, new technology capable of reliably diagnosing ovarian cancer in earlier stages could reduce the morbidity, high mortality and economic impact of this disease.

The system will work like a high-powered microscope that can be used to study tissue samples already removed. In addition, an endoscopic version is in the design stage to safely scan the ovaries for cancer during laparoscopic screenings in high-risk women, or as an adjunct to other laparoscopic procedures in all women.

The team will work with Dr. Kenneth D. Hatch, president of the Society of Pelvic Surgeons, and a professor of obstetrics and gynecology and director of female pelvic medicine and reconstructive surgery at the UA College of Medicine.

Through Hatch and a partnership with his patients who consent, Barton and Kostuk will be able to identify abnormal spatial and spectral markers of cancerous ovarian tissue.

Ray Kostuk

Ray Kostuk, Kenneth Von Behren Professor of Electrical and Computer Engineering & Professor of Optical Sciences, University of Arizona (Photo: Univ. of Arizona News)

The new imaging system will be tested on high-risk patients who are willing to participate and provide some future benefit to other patients who find themselves in a similar situation, Barton said.

Kostuk and Barton’s aim is to design the imaging system so that it is easy to use, requiring very little training, and also be cost effective.

“The system will image like an MRI or a CT scan but with much higher resolution than an ultrasonic image and will be a lot less expensive than an MRI. As an additional benefit no radiation will be used or exposed to sensitive ovary areas during the cancer screenings,” Kostuk said.

During the past 25 years Kostuk has researched different aspects of holography and holographic materials for use as optical elements.

The holographic imaging system being designed combines an optical technique that creates images capable of detecting subtle tissue microstructure changes. Together with fluorescence spectroscopy methods, the system has demonstrated capability for early cancer detection.

Another member of the team, UA research professor Marek Romanowski, with the UA department of biomedical engineering and the BIO5 Institute, is working on the development of targeted fluorescent dyes that will be used on tissue samples to identify or confirm suspected cancerous areas shown in the spatial image.

The multidisciplinary approach to the design of the hologram-based imaging system is a testament to the complexity of treating cancers.

“One of the advantages of being part of the UA is the ability to interact collaboratively with people in other disciplines,” Kotuk said. “Jennifer is a wonderful colleague who can identify important medical applications for new techniques and is able to bridge the gap between traditional engineering and medicine. Her skill and knowledge is critical to the success of the program,” he said.

“To solve the really interesting problems of today, no one person has all the expertise needed,” Barton added.

Sources:

Beyond BRCA1 & BRCA2: U.K. Researchers Identify Genetic Defect That Could Increase Risk of Ovarian Cancer Up To 40%

Scientists have located a region of DNA which – when altered – can increase the risk of ovarian cancer according to research published in Nature Genetics today. An international research group led by scientists based at the Cancer Research UK Genetic Epidemiology Unit, at the University of Cambridge and UCL (University College London) searched through the genomes of 1,810 women with ovarian cancer and 2,535 women without the disease from across the UK. …The scientists estimate that there is a 40 per cent increase in lifetime risk for women carrying the DNA variation on both copies of chromosome nine compared with someone who doesn’t carry it on either chromosome. The risk for women carrying the variation on both chromosomes is 14 in 1000 – compared with [10] ten in 1000 [in the general population]. … The lifetime risk for a woman carrying the DNA variant on one copy of the chromosome is increased by 20 per cent from ten in 1000 to 12 in 1000. …

Genetic link to ovarian cancer found

Cancer Research UK

SUNDAY 2 AUGUST 2009

Cancer Research UK Press Release

Scientists have located a region of DNA which – when altered – can increase the risk of ovarian cancer according to research published in Nature Genetics today.

An international research group led by scientists based at the Cancer Research UK Genetic Epidemiology Unit, at the University of Cambridge and UCL (University College London) searched through the genomes of 1,810 women with ovarian cancer and 2,535 women without the disease from across the UK. They analysed 2.5 million variations in DNA base pairs – the letters which spell out the genetic code – to identify common spelling ‘errors’ linked to ovarian cancer risk.

The scientists identified the genetic ‘letters’- called single nucleotide polymorphisms (SNPs) – which when spelled slightly differently increase ovarian cancer risk in some women. This is the first time scientists have found a SNP linked uniquely to risk of ovarian cancer and is the result of eight years of investigations. With the help of the international Ovarian Cancer Association Consortium (OCAC), they then looked at more than 7,000 additional women with ovarian cancer and 10,000 women without disease from around the world to confirm this finding.

Vodpod videos no longer available.

The region of risk DNA is located on chromosome nine – there are 23 pairs of each chromosome in humans, one of each pair inherited from each parent. The scientists estimate that there is a 40 per cent increase in lifetime risk for women carrying the DNA variation on both copies of chromosome nine compared with someone who doesn’t carry it on either chromosome. The risk for women carrying the variation on both chromosomes is 14 in 1000 – compared with [10] ten in 1000 [in the general population].

Approximately 15 per cent of women in the UK population carry two copies of the variant DNA.

The lifetime risk for a woman carrying the DNA variant on one copy of the chromosome is increased by 20 per cent from ten in 1000 to 12 in 1000. Approximately 40 per cent of women in the UK carry one copy.

Senior author Dr. Simon Gayther, whose work is supported by Cancer Research UK and The Eve Appeal charity which fundraises for the gynaecological cancer research team based at UCL, said: “The human DNA blueprint contains more than 10 million genetic variants. These are part and parcel of our characteristics and make-up – but a handful will also increase the chances of some women getting ovarian cancer and we have found the first one of these.”

“There is now a genuine hope that as we find more, we can start to identify the women at greatest risk and this could help doctors to diagnose the disease earlier when treatment has a better chance of being successful.”

Dr. Andrew Berchuck, head of the international Ovarian Cancer Association Consortium steering committee, said: “This study confirms that ovarian cancer risk is partly determined by genetic variants present in a large number of women. This initial discovery and others that will likely follow in the future lay the groundwork for individualised early detection and prevention approaches to reduce deaths from ovarian cancer.”

Ovarian cancer is the fifth most common cancer in women in the UK with around 6,800 new cases diagnosed each year in the UK – 130 women every week. It is the fourth most common cause of cancer death in women in the UK with around 4,300 deaths from the disease in the UK each year.

BRCA1 and BRCA2 are high risk genes which cause breast cancer and are already known to significantly increase the risk of ovarian cancer- but faults in these genes are rare and probably cause less than five per cent of all cases of ovarian cancer.

Lead author, Professor Dr Paul Pharoah, a Cancer Research UK senior research fellow at the University of Cambridge, said: “We already know that people with mistakes in the BRCA1 and BRAC2 genes have a greater risk of ovarian cancer – but on their own they don’t account for all of the inherited risk of the disease. “It is likely that the remaining risk is due to a combination of several unidentified genes – which individually carry a low to moderate risk. Now we have ticked one off, the hunt is on to find the rest.”

Rose Lammy, the mother of David Lammy MP [Member of Parliament] for Tottenham and Minister for Higher Education and Intellectual Property, died of ovarian cancer in 2008. Rose Lammy’s DNA sample was included in the study, and she carried both risk alleles of the new genetic marker that researchers have identified.

David Lammy said: “I am pleased that Mum’s sample was included in this study as it is one step towards earlier diagnosis of ovarian cancer when treatment is more successful. We now know the fact that she had this altered DNA meant that her lifetime risk had risen from 10 in 1,000 to 14 in 1,000, an increase of 40 per cent compared to those women who don’t carry this DNA variation. Dr Lesley Walker, director of cancer information at Cancer Research UK, added: “This is an important discovery. Our researchers have worked as part of a huge collaboration to establish the regions of DNA that can increase someone’s risk of developing ovarian cancer. “This research paves the way for scientists to discover even more genes linked to ovarian cancer and could lead to new approaches to treat or prevent the disease – crucially it will help doctors manage women who are at increased risk.”

Source: Genetic link to ovarian cancer found, Cancer Research U.K. Press Release & Video, 02 Aug. 09.

Reference: Honglin Song et al. (2009). A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2 Nature Genetics 10.1038/ng.424.

New Study Shows Four-Year Window for Early Detection of Ovarian Cancer

A new study by Howard Hughes Medical Institute researchers shows that most early stage ovarian tumors exist for years at a size that is a thousand times smaller than existing tests can detect reliably.  But the researchers say their findings also point to new opportunities for detecting ovarian cancer—a roughly four-year window during which most tumors are big enough to be seen with a microscope, but have not yet spread.

Tiny Early-Stage Ovarian Tumors Define Early Detection Challenge

Currently available tests detect ovarian cancer when it is about the size of the onion in the photograph. To reduce ovarian cancer mortality by 50 percent, an early detection test would need to be able to reliably detect tumors the size of the peppercorn. (Photo Source:  Patrick O. Brown, Howard Hughes Medical Institute Investigator, Research News Release, July 28, 2009)

Currently available tests detect ovarian cancer when it is about the size of the onion in the photograph. To reduce ovarian cancer mortality by 50 percent, an early detection test would need to be able to reliably detect tumors the size of the peppercorn. (Photo Source: Patrick O. Brown, Howard Hughes Medical Institute Investigator, Research News Release, July 28, 2009)

A new study by Howard Hughes Medical Institute researchers shows that most early stage ovarian tumors exist for years at a size that is a thousand times smaller than existing tests can detect reliably.

But the researchers say their findings also point to new opportunities for detecting ovarian cancer—a roughly four-year window during which most tumors are big enough to be seen with a microscope, but have not yet spread.

“Our work provides a picture of the early events in the life of an ovarian tumor, before the patient knows it’s there,” says Howard Hughes Medical Institute researcher Patrick O. Brown. “It shows that there is a long window of opportunity for potentially life-saving early detection of this disease, but that the tumor spreads while it is still much too small to be detected by any of the tests that have been developed or proposed to date.”

According to the American Cancer Society, some 15,000 women in the United States and 140,000 women worldwide die from ovarian cancer each year. The vast majority of these deaths are from cancers of the serous type, which are usually discovered only after the cancer has spread.

“Instead of typically detecting these cancers at a very advanced stage, detecting them at an early stage would be enormous in terms of saving lives,” says Brown, who is at Stanford University School of Medicine. Early detection would enable surgeons to remove a tumor before it spreads, he adds.

The article—co-authored by Chana Palmer of the Canary Foundation, a nonprofit organization focused on early cancer detection—was published July 28, 2009, in the open access journal PLoS Medicine.

“Like almost everything with cancer … the more closely you look at the problem, the harder it looks,” Brown says. “That’s not to say that I don’t believe it’s a solvable problem. It’s just a difficult one.” — Patrick O. Brown, M.D. Ph.D.

Patrick O. Brown, M.D. Ph.D., Howard Hughes Medical Institute Investigator, Stanford University School of Medicine

Patrick O. Brown, M.D. Ph.D., Howard Hughes Medical Institute Investigator, Stanford Univ. School of Medicine

“Like almost everything with cancer … the more closely you look at the problem, the harder it looks,” Brown says. “That’s not to say that I don’t believe it’s a solvable problem. It’s just a difficult one.”

In the quest to develop early detection methods for ovarian cancer, Brown says, science hasn’t had a firm grasp on its target. So he and Palmer took advantage of published data on ovarian tumors to generate a better understanding of how the cancer progresses in its earliest stages.

The team analyzed data on serous-type ovarian tumors that were discovered when apparently healthy women at high genetic [BRCA1 gene mutation] risk for ovarian cancer had their ovaries and fallopian tubes removed prophylactically. Most of the tumors were microscopic in size; they were not detected when the excised tissue was examined with the naked eye.

The analysis uncovered a wealth of unexplored information. Thirty-seven of the early tumors had been precisely measured when they were excised – providing new details about the size of the tumors when they were developing prior to intervention, Brown says. By extrapolating from this “occult” size distribution to the size distribution of larger, clinically evident tumors, the researchers were able to develop a model of how the tumors grew and progressed. “We are essentially trying to build a story for how these tumors progress that fits the data,” Brown explains.

Among the study’s findings:

  • Serous ovarian tumors exist for at least four years before they spread.
  • The typical serous cancer is less than three millimeters across for 90 percent of this “window of opportunity for early detection.”
  • These early tumors are twice as likely to be in the fallopian tubes as in the ovaries.
  • To cut mortality from this cancer in half, an annual early-detection test would need to detect tumors five millimeters in diameter or less – about the size of a black peppercorn and less than a thousandth the size at which these cancers are typically detected today.

Brown’s lab is now looking for ways to take advantage of that window of opportunity to detect the microscopic tumors and intervene before the cancer spreads.

One strategy the laboratory is pursuing is to examine tissues near the ovaries, in the female reproductive tract, for protein or other molecular markers that could signify the presence of cancer. Brown says answering another question might also prove helpful: whether there is any reliable flow of material from the ovaries and fallopian tubes through the uterus and cervix into the vagina—material that might be tested for a specific cancer marker.

Despite science’s broad understanding of cancer at a molecular level, it has been challenging to identify simple molecular markers that signal the presence of early disease. One current blood marker, CA-125, has proven useful in monitoring later-stage ovarian cancer, but it has not been helpful for early detection. So Brown’s lab is also looking for biomarkers that are present only in ovarian tumors and not in healthy cells, instead of relying on tests that look for unusually high levels of a molecule that is part of normal biology (like CA-125).

The researchers are doing extensive sequencing of all messenger RNA molecules (which carry information for the production of specific proteins) in ovarian cancer cells, searching for evidence of proteins in these cells that would never be found in non-cancer cells. These variant molecules could be produced as a result of chromosome rearrangements—when the genome is cut and spliced in unusual ways—in ovarian cancers. “It’s a long shot,” says Brown, “but it’s important enough to try.”

Source: Tiny Early-Stage Ovarian Tumors Define Early Detection Challenge, Research News, Howard Hughes Medical Institute, July 29, 2009 [summarizing Brown PO, Palmer C, 2009 The Preclinical Natural History of Serous Ovarian Cancer: Defining the Target for Early Detection. PLoS Med 6(7): e1000114. doi:10.1371/journal.pmed.1000114].

Vox Populi*: Libby, We’ll Be Missing You

Vox Populi:  Libby, We’ll Be Missing You.

voxpopDear Libby,

One year ago today, you left us after an extended battle with ovarian cancer.  You are missed as a wife, a daughter, a sister, an aunt and a cousin.  You were, and continue to be, a very special family member to your loved ones who remain behind.  You battled this insidious disease with courage but lost that battle in the prime of your life at age 26.

I wonder why your life was cut short by this disease.

I wonder why an effective screening test has not been discovered by a country that set a lofty goal of landing a man on the moon and accomplished that goal within a decade.

I wonder why there are so many pink ribbons yet so few teal ribbons.

I wonder how the mothers of a major Hollywood celebrity (Angelina Jolie) and the President of the U.S. (Barack Obama) could die from ovarian cancer, yet U.S. women remain generally unaware of the early warning signs and symptoms of the disease.

I have faith that you are in a much better place now.  A place that only knows pure love.  A place that knows no pain or suffering. A place where there are logical answers to my questions above.

I remember when you rode in my new red convertible sports car at the age of 11 with your blond hair blowing behind you in the wind.  At that moment, your life seemed limitless.

I remember when, as a young adult, you helped others who could not help themselves.  You chose generosity and kindness while many of your peers sought money and power.

I remember your positive attitude after initial diagnosis, despite the fact that you had every reason to blame life and others for your plight.

I remember your dry sense of humor after a doctor attempted to soften the blow of a disease recurrence diagnosis by telling you that even he could step out into the street tomorrow and get hit by a bus.  You suggested that the doctor needed serious help with his “people skills,” but joked that his insensitive statement should appear on an ovarian cancer fundraising T-shirt.

I remember how you continued to seek out medical solutions to your disease in the face of dire odds and statistics.

I remember “hearing” your smile on the telephone, regardless of our 3,000 mile separation.

I will always remember your example of love, faith, hope, courage, persistence, and ultimately, acceptance.

On July 28, 2008, I wrote about two songs that immediately came to mind after I heard about your passing.  One year later, two songs again come to mind based upon your inspiration and memory.

The first song is I’ll Be Missing You.

I’ll Be Missing You was written by Terry “Sauce Money” Carroll and performed by Sean “Diddy” Combs (then Puff Daddy), Faith Evans and 112.  Terry Carroll received a 1997 Grammy Award for the song that is based in part upon the melody of the 1983 Grammy Award-Winning song Every Breath You Take (written by Sting and performed by The Police).  I’ll Be Missing You was inspired by the memory of Combs’ fellow Bad Boy Records artist Christopher Wallace (aka Notorious B.I.G. ) who died in March 1997.  The song lyrics express what our family is feeling today when we think of you:

… Life ain’t always what it seem to be
Words can’t express what you mean to me
Even though you’re gone, we still a team
Through your family, I’ll fulfill your dream

In the future, can’t wait to see
If you open up the gates for me
Reminisce sometime
The night they took my friend
Try to black it out but it plays again
When it’s real feelings’ hard to conceal
Can’t imagine all the pain I feel
Give anything to hear half your breath
I know you still livin’ your life after death

… It’s kinda hard with you not around
Know you in heaven smilin down
Watchin us while we pray for you
Every day we pray for you
Til the day we meet again
In my heart is where I’ll keep you friend
Memories give me the strength I need to proceed
Strength I need to believe …
I still can’t believe you’re gone
Give anything to hear half your breath
I know you still living you’re life, after death …

The second song is Eva Cassidy’s cover of Over The Rainbow, which is the Academy Award-Winning song written by Harold Arlen and E.Y. Harburg, and originally sung by Judy Garland, in the 1939 Academy Award-Nominated “Best Picture” film Wizard of Oz.

Eva Cassidy, like you, died in the prime of her life from cancer.  Eva was 33 years old when she died in 1996 from melanoma, the deadliest form of skin cancer.  During her life, she created and sung beautiful music in relative obscurity. After her death, millions of worldwide fans “discovered” her music and today celebrate her life.  The lyrics of this classic ballad celebrate our belief that you are now at peace in a beautiful place “somewhere over the rainbow,” along with the hope that we will one day be reunited with you:

Somewhere over the rainbow
Way up high
There’s a land that I heard of
Once in a lullaby

Some day I’ll wish upon a star
And wake up where the clouds are far behind me
Where troubles melt like lemondrops
Away above the chimney tops
That’s where you’ll find me

Somewhere over the rainbow
Bluebirds fly
Birds fly over the rainbow
Why then, oh why can’t I?

In Mitch Albom’s bestselling memoir Tuesdays With Morrie, Morrie Schwartz, who was suffering from terminal Lou Gehrig’s Disease, taught Albom (his former college student) an important lesson about how death reminds us to live fully each day with love. “As long as we can love each other, and remember the feeling of love we had, we can die without ever really going away,” he told Albom one Tuesday. “All the love you created is still there. All the memories are still there. You live on in the hearts of everyone you have touched and nurtured while you were here. Death ends a life, not a relationship.”

Libby, your memory, love, and inspiration live on in our hearts and minds.  Your physical life ended one year ago, but your relationship with us is eternal.  We will forever love you.

Libby Remick (1982 - 2008) Grieve not, nor speak of me with tears, but laugh and talk of me as if I were beside you there. -- Isla Paschal Richardson

Libby Remick (1982 - 2008) "Grieve not, nor speak of me with tears, but laugh and talk of me as if I were beside you there." -- Isla Paschal Richardson

I am requesting family members and readers to honor Libby by contributing at least $1.00 to ovarian cancer research via the Ovarian Cancer Research Fund (and PayPal).  To make a contribution, click on Kelly Ripa’s picture located on the left homepage sidebar, or simply CLICK HERE.

__________________________

  • Ovarian cancer causes more deaths than any other cancer of the female reproductive system.
  • In 2009, the American Cancer Society (ACS) estimates that there will be approximately 21,550 new ovarian cancer cases diagnosed in the U.S.  ACS estimates that 14,600 U.S. women will die from the disease, or about 40 women per day.
  • Ovarian cancer is not a “silent” disease; it is a “subtle” disease. Recent studies indicate that some women may experience persistent, nonspecific symptoms, such as (i) bloating, (ii) pelvic or abdominal pain, (iii) difficulty eating or feeling full quickly, or (iv) urinary urgency or frequency. Women who experience such symptoms daily for more than a few weeks should seek prompt medical evaluation. To learn more about the warning signs and symptoms of ovarian cancer, CLICK HERE.
  • Ovarian cancer can afflict adolescent, young adult, and mature women, although the risk of disease increases with age and peaks in the late 70s. Pregnancy and the long-term use of oral contraceptives reduce the risk of developing ovarian cancer.
  • There is no reliable screening test for the detection of early stage ovarian cancer. Pelvic examination only occasionally detects ovarian cancer, generally when the disease is advanced. A Pap smear cannot detect ovarian cancer. However, the combination of a thorough pelvic exam, transvaginal ultrasound, and a blood test for the tumor marker CA125 may be offered to women who are at high risk of ovarian cancer and to women who have persistent, unexplained symptoms like those listed above.
  • If diagnosed at the localized stage, the 5-year ovarian cancer survival rate is 92%; however, only about 19% of all cases are detected at this stage, usually fortuitously during another medical procedure.
  • For women with regional and distant metastatic disease, the 5-year ovarian cancer survival rates are 71% and 30%, respectively. The 10-year relative survival rate for all stages combined is 38%.

__________________________

*”Vox Populi,” a Latin phrase that means “voice of the people,” is a term often used in broadcast journalism to describe an interview of a “man on the street.”

In the spirit of Vox Populi, Libby’s H*O*P*E*™ searches online for original pieces of writing created by ovarian cancer survivors, survivors’ family members, cancer advocates, journalists, and health care professionals, which address one or more aspects of ovarian cancer within the context of daily life. The written pieces that we discover run the gamut; sometimes poignant, sometimes educational, sometimes touching, sometimes comedic, but always honest. The written piece may be an essay, editorial, poem, letter, or story about a loved one. In all cases, we have received permission from the writer to publish his or her written piece as a Libby’s H*O*P*E*™ Vox Populi weblog post.

It is our hope that the monthly Vox Populi feature will allow readers to obtain, in some small way, a better understanding of how ovarian cancer impacts the life of a woman diagnosed with the disease and her family. We invite all readers to submit, or bring to our attention, original written pieces suitable for publication as monthly Vox Populi features.


Women’s Gynecological Exams: Another Victim Of The Troubled Economy?

“… At Mother’s Day, a new survey from the National Ovarian Cancer Coalition (NOCC), http://www.ovarian.org, reveals some startling facts about women’s health: more than 52 percent of women expect the economy will impact their gynecological health choices, in many cases delaying or skipping their annual gynecological exams altogether.”

Continue reading

M.D. Anderson Study Predicts Dramatic Growth in Cancer Rates Among U.S. Elderly, Minorities

” … Over the next 20 years, the number of new cancer cases diagnosed annually in the United States will increase by 45 percent, from 1.6 million in 2010 to 2.3 million in 2030, with a dramatic spike in incidence predicted in the elderly and minority populations, according to research from The University of Texas M. D. Anderson Cancer Center. …Given these statistics, the role of screening and prevention strategies becomes all the more vital and should be strongly encouraged, said [Ben] Smith [M.D.]. … These findings also highlight two issues that must be addressed simultaneously: clinical trial participation and the increasing cost of cancer care. Historically, both older adults and minorities have been under-represented in such studies, and, therefore, vulnerable to sub-optimal cancer treatment. Simultaneously, over the past decade in particular, the cost of cancer care is growing at a rate that’s not sustainable. …”

“Research underscores impact on health care system, importance of screenings, prevention strategies, inclusive clinical trials

Cancer Newsline Podcast
M. D. Anderson audio player (click & play)
Dramatic Growth in Cancer Rates Among Elderly, Minorities

Over the next 20 years, the number of new cancer cases diagnosed annually in the United States will increase by 45 percent, from 1.6 million in 2010 to 2.3 million in 2030, with a dramatic spike in incidence predicted in the elderly and minority populations, according to research from The University of Texas M. D. Anderson Cancer Center.

The study, published online today in Journal of Clinical Oncology, is the first to determine such specific long-term cancer incidence projections. It predicts a 67 percent increase in the number of adults age-65-or-older diagnosed with cancer, from 1 million in 2010 to 1.6 million in 2030. In non-white individuals over the same 20-year span, the incidence is expected to increase by 100 percent, from 330,000 to 660,000.

Ben Smith, M.D., Adjunct Assistant Professor, Department of Radiation Oncology, The University of Texas M.D. Anderson Center

Ben Smith, M.D., Adjunct Assistant Professor, Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center

According to Ben Smith, M.D., adjunct assistant professor in M. D. Anderson’s Department of Radiation Oncology, the study underscores cancer’s growing stress on the U.S. health care system.

‘In 2030, 70 percent of all cancers will be diagnosed in the elderly and 28 percent in minorities, and the number of older adults diagnosed with cancer will be the same as the total number of Americans diagnosed with cancer in 2010,’ said Smith, the study’s senior author. ‘Also alarming is that a number of the types of cancers that are expected to increase, such as liver, stomach and pancreas, still have tremendously high mortality rates.’

Unless specific prevention and/or treatment strategies are discovered, cancer death rates also will increase dramatically, said Smith, who is currently on active military duty and is stationed at Lackland Air Force Base.

To conduct their research, Smith and his team accessed the United States Census Bureau statistics, updated in 2008 to project population growth through 2050, and the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) registry, the premier population-based cancer registry representing 26 percent of the country’s population. Cancer incidence rates were calculated by multiplying the age, sex, race and origin-specific population projections by the age, sex, race and origin-specific cancer incidence rates.

The researchers found that from 2010 to 2030, the population is expected to grow by 19 percent (from 305 to 365 million). The total number of cancer cases will increase by 45 percent (from 1.6 to 2.3 million), with a 67 percent increase in cancer incidence in older Americans (1 to 1.6 million), compared to an 11 percent increase in those under the age of 65 (.63 to .67 million).

With respect to race, a 100 percent increase in cancer is expected for minorities (.33 to .66 million); in contrast, in white Americans, a 31 percent increase is anticipated (1.3 to 1.7 million). The rates of cancer in blacks, American Indian-Alaska Native, multi-racial, Asian-Pacific Islanders and Hispanics will increase by 64 percent, 76 percent, 101 percent, 132 percent and 142 percent, respectively.

Regarding disease-specific findings, Smith and his team found that the leading cancer sites are expected to remain constant – breast, prostate, colon and lung. However, cancer sites with the greatest increase in incidence expected are: stomach (67 percent); liver (59 percent); myeloma (57 percent); pancreas (55 percent); and bladder (54 percent).

Given these statistics, the role of screening and prevention strategies becomes all the more vital and should be strongly encouraged, said Smith. In the study, Smith and his team site [sic]: vaccinations for hepatitis B and HPV; the chemoprevention agents tamoxifen and raloxifene; interventions for tobacco and alcohol; and removal of pre-malignant lesions, such as colon polyps.

These findings also highlight two issues that must be addressed simultaneously: clinical trial participation and the increasing cost of cancer care. Historically, both older adults and minorities have been under-represented in such studies, and, therefore, vulnerable to sub-optimal cancer treatment. Simultaneously, over the past decade in particular, the cost of cancer care is growing at a rate that’s not sustainable.

‘The fact that these two groups have been under-represented in clinical research participation, yet their incidence of cancer is growing so rapidly, reflects the need for therapeutic trials to be more inclusive and address issues that are particularly relevant to both populations,’ said Smith. ‘In addition, as we design clinical trials, we need to seek not only the treatment that will prolong survival, but prolong survival at a reasonable cost to patients. These are two issues that oncologists need to be much more concerned about and attuned to.’

Another issue that needs to be addressed is the shortage of health care professionals predicted. For example, according to a workforce assessment by American Society for Clinical Oncology (ASCO), the shortage of medical oncologists will impact the health care system by 2020. Smith said ASCO and other professional medical organizations beyond oncology are aware of the problem, and are actively engaged in efforts to try and grow the number of physicians, as well as encourage the careers of nurse practitioners and physician assistants who are part of the continuum of care, to best accommodate the increase in demand forecasted.

‘There’s no doubt the increasing incidence of cancer is a very important societal issue. There will not be one solution to this problem, but many different issues that need to be addressed to prepare for these changes,’ said Smith. ‘I’m afraid if we don’t come to grips with this as a society, health care may be the next bubble to burst.’

In addition to Smith, other M. D. Anderson authors on the study include: Thomas Buchholz, M.D., professor and chair of the Department of Radiation Oncology and the study’s senior author; Gabriel Hortobagyi, M.D., professor and chair of the Department of Breast Medical Oncology; and Grace Smith, M.D., Ph.D., assistant professor in the Department of Radiation Oncology. Arti Hurria, M.D., post-doctoral fellow in the Department of Medical Oncology, City of Hope Cancer Center, also is a contributing author on the study.”

Sources:

President of M.D. Anderson Outlines 10 Steps To Achieve Progress Against Cancer.

“The Houston Chronicle recently published a commentary by John Mendelsohn, M.D., president of M. D. Anderson, outlining actions the nation should take to achieve great progress against cancer. … Here are 10 steps we can take to ensure that deaths decrease more rapidly, the ranks of survivors swell, and an even greater number of cancers are prevented in the first place. …”

“Ten Pieces Help Solve Cancer Puzzle

John Mendelsohn, M.D., President, The University of Texas M.D. Anderson Cancer Center

John Mendelsohn, M.D., President, The University of Texas M.D. Anderson Cancer Center

The Houston Chronicle recently published a commentary by John Mendelsohn, M.D., president of M. D. Anderson, outlining actions the nation should take to achieve great progress against cancer.

An American diagnosed with cancer today is very likely to join the growing ranks of survivors, who are estimated to total 12 million and will reach 18 million by 2020. The five-year survival rate for all forms of cancer combined has risen to 66%, more than double what it was 50 years ago.

Along with the improving five-year survival rates, the cancer death rate has been falling by 1% to 2% annually since 1990.

According to the World Health Organization, cancer will be the leading worldwide cause of death in 2010. Over 40% of Americans will develop cancer during their lifetime.

While survival rates improve and death rates fall, cancer still accounts for one in every five deaths in the U.S., and cost this nation $89.0 billion in direct medical costs and another $18.2 billion in lost productivity during the illness in 2007, according to the National Institutes of Health.

Here are 10 steps we can take to ensure that deaths decrease more rapidly, the ranks of survivors swell, and an even greater number of cancers are prevented in the first place.

#1.  Therapeutic cancer research should focus on human genetics and the regulation of gene expression.

Cancer is a disease of cells that have either inherited or acquired abnormalities in the activities of critical genes and the proteins for which they code. Most cancers involve several abnormally functioning genes – not just one – which makes understanding and treating cancer terribly complex. The good news is that screening for genes and their products can be done with new techniques that accomplish in days what once took years.

Knowledge of the human genome and mechanisms regulating gene expression, advances in technology, experience from clinical trials, and a greater understanding of the impact of environmental factors have led to exciting new research approaches to cancer treatment, all of which are being pursued at M. D. Anderson:

  • Targeted therapies.  These therapies are designed to counteract the growth and survival of cancer cells by modifying, replacing or correcting abnormally functioning genes or their RNA and protein products, and by attacking abnormal biochemical pathways within these cells.
  • Molecular markers.  Identifying the presence of particular abnormal genes and proteins in a patient’s cancer cells, or in the blood, will enable physicians to select the treatments most likely to be effective for that individual patient.
  • Molecular imaging.  New diagnostic imaging technologies that detect genetic and molecular abnormalities in cancers in individual patients can help select optimal therapy and determine the effectiveness of treatment within hours.
  • Angiogenesis.  Anti-angiogenesis agents and inhibitors of other normal tissues that surround cancers can starve the cancer cells of their blood supply and deprive them of essential growth-promoting factors which must come from the tumor’s environment.
  • Immunotherapy. Discovering ways to elicit or boost immune responses in cancer patients may target destruction of cancer cells and lead to the development of cancer vaccines.

#2.  Better tests to predict cancer risk and enable earlier detection must be developed.

New predictive tests, based on abnormalities in blood, other body fluids or tissue samples, will be able to detect abnormalities in the structure or expression of cancer-related genes and proteins. Such tests may predict the risk of cancer in individuals and could detect early cancer years before any symptoms are present.

The prostate-specific antigen test for prostate cancer currently is the best known marker test to detect the possible presence of early cancer before it has spread. Abnormalities in the BRCA 1 and BRCA 2 genes predict a high risk for breast cancer, which can guide the decisions of physicians and patients on preventive measures. Many more gene-based predictors are needed to further our progress in risk assessment and early detection.

#3.  More cancers can and must be prevented.

In an ideal world, cancer “care” would begin with risk assessment and counseling of a person when no malignant disease is present. Risk factors include both inherited or acquired genetic abnormalities and those related to lifestyle and the environment.

The largest risk factor for cancer is tobacco smoking, which accounts for nearly one-third of all cancer deaths. Tobacco use should be discouraged with cost disincentives, and medical management of discontinuing tobacco use must be reimbursed by government and private sector payors.

Cancer risk assessment should be followed by appropriate interventions (either behavioral or medical) at a pre-malignant stage, before a cancer develops. Diagnosis and treatment of a confirmed cancer would occur only when these preventive measures fail.

A full understanding of cancer requires research to identify more completely the genetic, environmental, lifestyle and social factors that contribute to the varying types and rates of cancer in different groups in this country and around the world. A common cancer in Japan or India, for example, often is not a common cancer in the U.S. When prostate cancer occurs in African-Americans it is more severe than in Caucasians. A better understanding of the factors that influence differences in cancer incidence and deaths will provide important clues to preventing cancer in diverse populations worldwide.

#4.  The needs of cancer survivors must become a priority.

Surviving cancer means many things: reducing pain, disability and stress related to the cancer or the side effects of therapy; helping patients and their loved ones lead a full life from diagnosis forward; preventing a second primary cancer or recurrence of the original cancer; treating a difficult cancer optimally to ensure achieving the most healthy years possible, and more.  Since many more patients are surviving their cancers – or living much longer with cancer – helping them manage all the consequences of their disease and its treatment is critically important.  It is an area ripe for innovative research and for improvement in delivery of care.

#5.  We must train future researchers and providers of cancer care.

Shortages are predicted in the supply of physicians, nurses and technically trained support staff needed to provide expert care for patients with cancer.  On top of this, patient numbers are projected to increase.  We are heading toward a “perfect storm” unless we ramp up our training programs for cancer professionals at all levels.   The pipeline for academic researchers in cancer also is threatened due to the increasing difficulty in obtaining peer-reviewed research funding. We must designate more funding from the NIH and other sources specifically for promising young investigators, to enable them to initiate their careers.

#6.  Federal funding for research should be increased.

After growing by nearly 100% from 1998-2002, the National Cancer Institute budget has been in decline for the past four years. Through budget cuts and the effects of inflation, the NCI budget has lost approximately 12% of its purchasing power.  Important programs in tobacco control, cancer survivorship and support for interdisciplinary research have had significant cuts.  The average age at which a biomedical researcher receives his or her first R01 grant (the gold standard) now stands at 42, hardly an inducement to pursue this field. This shrinks the pipeline of talented young Americans who are interested in careers in science, but can find easier paths to more promising careers elsewhere.  Lack of adequate funding also discourages seasoned scientists with outstanding track records of contributions from undertaking innovative, but risky research projects.  The U.S. leadership in biomedical research could be lost.

Biomedical research in academic institutions needs steady funding that at least keeps up with inflation and enables continued growth.

#7.  The pace of clinical research must accelerate.

As research ideas move from the laboratory to patients, they must be assessed in clinical trials to test their safety and efficacy. Clinical trials are complicated, lengthy and expensive, and they often require large numbers of patients.  Further steps must be taken to ensure that efficient and cost-effective clinical trials are designed to measure, in addition to outcomes, the effects of new agents on the intended molecular targets. Innovative therapies should move forward more rapidly from the laboratory into clinical trials.

The public needs to be better educated about clinical trials, which in many cases may provide them with access to the best care available.  Greater participation in trials will speed up drug development, in addition to providing patients with the best options if standard treatments fail.  The potential risks and benefits of clinical trials must continue to be fully disclosed to the patients involved, and the trials must continue to be carefully monitored.

The issue of how to pay for clinical trials must be addressed. The non-experimental portion of the costs of care in clinical trials currently are borne in part by Medicare, and should be covered fully by all payors. The experimental portion of costs of care should be covered by the owner of the new drug, who stands to benefit from a new indication for therapeutic use.

#8.  New partnerships will encourage drug and device development.

One way to shorten the time for drug and device development is to encourage and reward collaboration among research institutions, and collaboration between academia and industry.  Increasingly, partnerships are required to bring together sufficient expertise and resources needed to confront the complex challenges of treating cancer. There is enormous opportunity here, but many challenges, as well.

Academic institutions already do collaborate, but we need new ways to stimulate increased participation in cooperative enterprises.

Traditionally, academic institutions have worked with biotech and pharmaceutical companies by conducting sponsored research and participating in clinical trials.  By forming more collaborative alliances during the preclinical and translational phases prior to entering the clinic, industry and academia can build on each other’s strengths to safely speed drug development to the bedside. The challenge is that this must be done with agreements that involve sharing, but also protect the property rights and independence of both parties.

The results of all clinical trials must be reported completely and accurately, without any influence from conflicts of interest and with full disclosure of potential conflicts of interest.

#9. We must provide access to cancer care for everyone who lives in the U.S.

More than 47 million Americans are uninsured, and many others are underinsured for major illnesses like cancer. Others are uninsurable because of a prior illness such as cancer.  And many are indigent, so that payment for care is totally impossible.

Depending on where they live and what they can afford, Americans have unequal access to quality cancer care. Treatment options vary significantly nationwide. We must find better ways to disseminate the best standards of high-quality care from leading medical centers to widespread community practice throughout the country.

Cancer incidence and deaths vary tremendously among ethnic and economic groups in this country. We need to address the causes of disparities in health outcomes and move to eliminate them.

We are unique among Western countries in not providing direct access to medical care for all who live here. There is consensus today among most Americans and both political parties that this is unacceptable.  Especially for catastrophic illnesses like cancer, we must create an insurance system that guarantees access to care.

A number of proposals involving income tax rebates, vouchers, insurance mandates and expanded government insurance programs address this issue. Whatever system is selected should ensure access and include mechanisms for caring for underserved Americans.  The solution will require give-and-take among major stakeholders, many of which benefit from the status quo.  However, the social and economic costs have risen to the point that we have no choice.

#10.  Greater attention must be paid to enhancing the quality of cancer care and reducing costs.

New therapies and medical instruments are expensive to develop and are a major contributor to the rising cost of medical care in the U.S.  The current payment system rewards procedures, tests and treatments rather than outcomes.  At the same time, cancer prevention measures and services are not widely covered.  A new system of payment must be designed to reward outcomes, as well as the use of prevention services.

Quality of care can be improved and costs can be reduced by increasing our efforts to reduce medical errors and to prescribe diagnostic tests and treatments only on the basis of objective evidence of efficacy.

A standardized electronic medical record, accessible nationwide, is essential to ensuring quality care for patients who see multiple providers at multiple sites, and we are far behind many other nations.  Beyond that, a national electronic medical record could provide enormous opportunities for reducing overhead costs, identifying factors contributing to many illnesses (including cancer), determining optimal treatment and detecting uncommon side effects of treatment.

What the future holds in store.

I am optimistic. I see a future in which more cancers are prevented, more are cured and, when not curable, more are managed as effectively as other chronic, life-long diseases. I see a future in which deaths due to cancer continue to decrease.

Achieving that vision will require greater collaboration among academic institutions, government, industry and the public.  Barriers to quality care must be removed.  Tobacco use must be eradicated.  Research must have increased funding.  Mindful that our priority focus is on the patient, we must continue to speed the pace of bringing scientific breakthroughs from the laboratory to the bedside.

M. D. Anderson resources:

John Mendelsohn, M.D.”

Primary SourceTen Pieces Help Solve Cancer Puzzle, by John Mendelsohn, M.D., Feature Article, The University of Texas M.D. Anderson Cancer Center Cancer News, Mar. 2009.

The Rock Band “N.E.D.”: Their Medical Skills Save Many; Their Music Could Save Thousands

When spoken by a doctor, the medical term “N.E.D.” – No Evidence of Disease – is music to the ears of an ovarian cancer survivor.   A band of doctors, called “N.E.D.,” wants to be music to the ears of the general public when it comes to raising awareness about women’s cancers. …During the day, this eclectic group of highly skilled physicians perform under the bright lights of the operating room while caring for women who are battling gynecological cancers.  By night, these physicians turn into artists who play a mix of rock and alternative rock music to give a voice to the needs, struggles, and triumphs of their cancer patients. … Victor Hugo, the French author of the classic novels Les Misérables and Notre-Dame de Paris (The Hunchback of Notre Dame), once said, “music expresses that which cannot be said and on which it is impossible to be silent.”  The band N.E.D. believes in the same principle when it comes to the promotion of gynecologic cancer awareness and education through music.  The N.E.D. band members will save many women’s lives throughout their medical careers; however, they could very well save thousands of lives through the educational cancer awareness message brought to light through their music.

Explanation of LOGO:Pink for breast cancer, yellow is the symbolic color for hope, teal for gyn cancer, the other three colors are just complimentary, but there are six colors total, one for each band member.

Explanation of the N.E.D. Logo: Pink for Breast Cancer, Yellow is the Symbolic Color for Hope, Teal for Gynecologic Cancer; the Remaining Three Colors are Just Complimentary, But There Are Six Colors Total, One for Each Band Member. (Photo Source: Motema Music)

When spoken by a doctor, the medical term “N.E.D.” – No Evidence of Disease – is music to the ears of an ovarian cancer survivor.   A band of doctors, called “N.E.D.,” wants to be music to the ears of the general public when it comes to raising awareness about women’s cancers.  Yes, you read that correctly, six gynecologic oncologists want to raise awareness about ovarian cancer and other women’s cancers through their music. During the day, this eclectic group of highly skilled physicians perform under the bright lights of the operating room while caring for women who are battling gynecological cancers.  By night, these physicians turn into artists who play a mix of rock and alternative rock music to give a voice to the needs, struggles, and triumphs of their cancer patients.

The members of N.E.D. are set forth below.

On drums and percussion as well as guitar is Nimesh P. Nagarsheth, Assistant Professor, Division of Gynecologic Oncology, Mount Sinai Medical Center, New York, New York & Englewood Hospital and Medical Center, Englewood, New Jersey.

On lead guitar is William E. Winter, III, M.D., Northwest Cancer Specialists, Portland, Oregon.

On bass guitar, harmonica and vocals, William R. (Rusty) Robinson, M.D. FACS, FACOG. , Professor, Director of Clinical Research, Harrington Cancer Center, Texas Tech University Health Science Center, Amarillo, Texas.

On guitar and lead vocals, John F. Boggess, M.D., Associate Professor, Fellowship Program Director, Gynecology Oncology, Director, Robotic Assisted Medicine Center, University of North Carolina at Chapel Hill.

On lead vocals and guitar, Joanie Hope, M.D., Fellow, Gynecologic Oncology, New York University Langone Medical Center, New York, New York.

On guitar, John T. Soper, M.D., The Hendricks Professor of Obstetrics and Gynecology, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill.

The Backstory

Most of the N.E.D. band members played in musical groups during their youth. Nimesh Nagarsheth’s interest in music relates back to his college days. As a student at the University of Wisconsin, Nagarsheth focused on musical percussion study, but later, due to pragmatism, he refocused his concentration on medicine. “I saw many really talented peers who worked really hard and were not getting jobs as musicians.” “Music has always been a passion of mine, ever since I was a child,” said Nagarsheth,. “But to be honest with you, I didn’t really develop an interest in medicine until I went to college.”

While in medical school in Oregon, John Boggess played in a band with other medical students in the 1980s to earn rent money, and he developed a small following.  But, Boggess gave up musical pursuits to practice medicine.  Joanie Hope said that she has been musical since she was a child: “When I was in medical school, I wrote lots of songs with medical themes, because medicine is, after all, about people and their troubles. When I was in residency, I didn’t have time to do much with music, but now that I’ve found this band, I’m able to tap into my creative energy again.”  John Soper played in high school and college bands, and as an adult was a member of a local bluegrass group called Piney Mountain Boys, which split up in 1989.

Oddly enough, the creation of N.E.D. arose from an immediate need for entertainment at the 2008 annual meeting of the Society of Gynecologic Oncologists (SGO).  In short order, the six gynecologic oncologists met and rehearsed in preparation for the gig.  Notably, with the exception of John Soper and John Boggess, the band members never met, much less played together. They rehearsed one night, and performed the next. William Winter,  a band member, said he and his colleagues were game to play for their peers, but noted that “[n]one of us are known for our music.” As stated in the vernacular by John Soper, the goal “was to not suck.” Despite the band’s hasty creation and short preparation time, the doctors who attended the SGO meeting loved the band’s music and rocked out on Led Zeppelin and Allman Brothers Band songs. The band played the 30 or so classic covers that they rehearsed, and when the large crowd of doctors asked for more, the band performed the same songs again. “People were sticking around,” Winter said. “We didn’t get booed off the stage. We actually got asked to do some encores. We played everything we know. We had to replay songs.” Marsha Wilson, communications director for the Gynecologic Cancer Foundation (GCF), said ” “Everybody went crazy. They were really good.”

After receiving positive feedback for its performance at the 2008 SGO Annual Meeting, N.E.D. went on to perform at the First National Gynecologic Cancer Symposium and played at Arlington National Cemetery in front of the memorial to military women who died in the line of duty. After several more successful gigs, the seeds were planted for a band that would be devoted entirely to raising gynecologic cancer awareness and funding for disease screening, clinical trials, and patient education.

The Band’s Mission of Gynecologic Cancer Awareness & Education

“Do you ever see the words gynecologic oncology in print?” asked John Boggess.  Boggess’ comment carries the underlying message that gynecological cancers are often overlooked, and reveals the overarching charitable mission of N.E.D. In a world where “me first” mentality is commonplace, and rock stars drive ultra-luxury sports cars, run with entourages, and make a habit of attending rehab, these multifaceted doctors simply want to raise the general public’s awareness about women’s cancers.  “We think that people need to understand about these diseases and the women who have them,” said John Boggess. “So anything that we can do outside of the surgery we do every day in the operating room and in the clinic, we find to be an incredible privilege.”

In 2008, several band members were asked about the future potential of N.E.D. as a vehicle for cancer awareness.  At that time, Joanie Hope stated that she wanted a future for the band that would “speak to people” through music. “I want people to listen to us at home so that our music and lyrics reflect what they are feeling if they have cancer, or someone they love does,” said Hope. Nimesh Nagarsheth responded, “I’d like us to make a CD.  We could sell them at concerts as a fundraising tool, and we could put educational inserts about women’s cancer inside the case.  Joanie [Hope] and I, as the ‘New York division of N.E.D.,’ have already written ten original songs, some with lyrics about cancer …”

Each original song written by the band was inspired by the doctors’ work with women’s cancers.  Joanie Hope wrote a song entitled, “Rhythm Heals,” which is intended to inspire her patients.  “It encompasses what we’re all about,” said Hope. “There are many ways to heal beyond what we do as doctors. My patients teach me that all the time.” Nimesh Nagarsheth wrote the song “Third-Person Reality” to address a doctor’s struggle to help patients dealing with cancer diagnoses.  “It’s tempting to remove yourself from the situation and be like a third person,” said Nagarsheth, “but we have to overcome that because our patients need us.”  The hard-rocking track “False Pretenses,” written by William Winter and sung by John Boggess, urges genuine communication when time is short due to a patient’s dire diagnosis.

Motéma Music & The Gynecologic Cancer Foundation Take Interest

NED Group Picture

Meet The Band: (Bottom Row) John Boggess; (Center Row, left to right) Nimesh Nagarsheth, Joanie Hope, William Winter, William (Rusty) Robinson; (Top Row) John Soper. (Photo Source: N.E.D. Facebook Page)

The 2008 comments made by Joanie Hope and Nimesh Nagarsheth in regard to N.E.D.’s future were indeed prophetic. Shortly thereafter, the band landed a record deal with Motéma Music, a New York record label that features world music and jazz musicians.  Motéma artist K.J. Denhert is currently working with the band as a performance and songwriting coach. Mario McNulty, who has worked with David Bowie, Linkin’ Park and other classic rock bands, will produce the band’s first album.

N.E.D.’s first album is set for release in November 2009 during Gynecologic Cancer Month. Although the band wants to appeal to cancer patients and their families, William Winter said that they also want to reach others who may not be aware of the other types of cancers that afflict women. Winter’s hope is to “market it to anyone and everyone . . . and have them understand what goes on with women’s cancers, and the pain behind these things and what women feel and what cancer patients feel and go through.”

N.E.D. also receives support from the GCF.  GCF believes that N.E.D.’s efforts are consistent with its charitable and educational mission. In fact, the band will be featured as part of a GCF national campaign, the Gynecologic Cancer Awareness Movement, which is scheduled to kick off in November 2009 in Washington D.C.  Although the band has received support from GCF, additional monies are needed to fund the band’s CD recording and post-production costs. GCF is accepting donations and soliciting funds to support the production of the band’s first CD. Any future proceeds from the sale of the CD and live performances will be donated to the Gynecologic Cancer Foundation (GCF) whose mission is to educate the public about gynecologic cancers and support promising research.  You can help by making a donation to the GCF (marked with a designation for “N.E.D.”) through one of the methods provided below.

*          *          *          *

Online Contribution (Through the Network for Good):

CLICK HERE to donate now.

By Mail:

Mail your tax deductible contribution to:
The Gynecologic Cancer Foundation
230 W. Monroe, Suite 2528
Chicago, Il. 60606-4703
CLICK HERE for a donation form (Microsoft Word Document) to mail in with your contribution.

By Telephone:

Call GCF at 312-578-1439 and donate with a credit card

*          *          *          *

In addition to landing the Motéma record contract, N.E.D. has been invited to appear on “The Bonnie Hunt Show,” and is in discussions with CBS and ABC with respect to potential appearances on “The Early Show” and “Good Morning America,” respectively.  Also, the band hopes to obtain an audience with Oprah Winfrey.

Their Medical Skills Save Many; Their Music Could Save Thousands

The importance of N.E.D. and its mission to raise women’s cancer awareness is best understood through the eyes of a gynecologic cancer patient.  Samantha Hill, one of Nimesh Nagarsheth’s patients, was diagnosed with ovarian cancer at a young age.  Samantha says that when she learned that her doctor played in a rock band, she was not surprised. Hill emphasized that it is her greatest hope that N.E.D.’s message gets across to the general public.  “You’re 35 years old and you hear that you have cancer, and you’re in shock,” she recalls. “I felt that he [Nagarsheth] could relate and I think music is a very important tool.  And I think that specifically, ovarian cancer, there’s not much awareness and it’s really a silent killer.”

Victor Hugo, the French author of the classic novels Les Misérables and Notre-Dame de Paris (The Hunchback of Notre Dame), once said, “music expresses that which cannot be said and on which it is impossible to be silent.”  The band N.E.D. believes in the same principle when it comes to promotion of gynecologic cancer awareness and education through music.  The N.E.D. band members will save many women’s lives throughout their medical careers; however, they could very well save thousands of lives through the educational cancer awareness message brought to light through their music.

N.E.D. Band Rehearsal 1, December 7, 2008  (Motema artist KJ Denhert working with the band)


__________________________________________________

About Gynecologic Cancers & Gynecologic Oncologists

Gynecologic cancers originate in the female reproductive organs, including the cervix, ovaries, uterus, fallopian tubes, vagina and vulva.  Every woman is at risk for developing a gynecologic cancer. It is estimated that there were approximately 78,000 new cases diagnosed, and approximately 28,000 deaths, from gynecologic cancers in the United States during 2008.

Gynecologic oncologists are physicians committed to the comprehensive treatment of women with cancer. After completing four years of medical school and four years of residency in obstetrics and gynecology, these physicians pursue an additional three to four years of training in gynecologic oncology through a rigorous fellowship program overseen by the American Board of Obstetrics and Gynecology. Gynecologic oncologists are not only trained to be skilled surgeons capable of performing wide-ranging cancer operations, but they are also trained in prescribing the appropriate chemotherapy for those conditions and/or radiation therapy when indicated. Frequently, gynecologic oncologists are involved in research studies and clinical trials that are aimed at finding more effective and less toxic treatments to further advance the field and improve cure rates.  Studies on outcomes from gynecologic cancers, especially ovarian cancer, demonstrate that women treated by a gynecologic oncologist have a better likelihood of prolonged  survival compared to care rendered by non-specialists. Due to their extensive training and expertise, gynecologic oncologists often serve as the “team captain” who coordinates all aspects of a woman’s cancer care and recovery. Gynecologic oncologists understand the impact of cancer and its treatments on all aspects of women’s lives, including future childbearing, sexuality, physical and emotional well-being, and the impact cancer can have on the patient’s whole family.  But, there are only about 1,000 board-certified gynecologic oncologists in the United States.  Women may need to ask their primary care provider for referral to a gynecologic oncologist if a gynecologic cancer is suspected because not all physicians are aware of the practice scope of modern gynecologic oncologists. Women can find a gynecologic oncologist by going online to www.wcn.org and clicking on the find a doctor button. This simple step may be the first stride forward to long-term survivorship and cure.  It’s important to start gynecologic cancer care with the right team and a winning game plan.

About the Gynecologic Cancer Foundation

The Gynecologic Cancer Foundation (GCF) is a 501(c)(3) not-for-profit organization whose mission is to ensure public awareness of gynecologic cancer prevention, early diagnosis and proper treatment. In addition, GCF supports research and training related to gynecologic cancers. GCF advances this mission by increasing public and private funds that aid in the development and implementation of programs to meet these goals. For more information about GCF, its educational materials or research grants, please visit www.thegcf.org or contact GCF Headquarters by phone at 312-578-1439 or by e-mail at info@thegcf.org.  For additional information on gynecologic cancers or a referral to a gynecologic oncologist or a related specialist, please call the toll-free GCF Information Hotline at 800-444-4441.  For more information about women’s cancers, visit GCF’s Women’s Cancer Network Web site:  www.wcn.org. Log on for a confidential risk assessment to learn about your risk for developing gynecologic and breast cancers. Comprehensive information about each gynecologic cancer and breast cancer is available on the site. The site also provides the opportunity to locate a nearby gynecologic oncologist, a step women are urged to take if they suspect or have been diagnosed with a gynecologic cancer.

Primary Sources:

N.E.D. Band Bio, Artist Profile, Motéma Music.

N.E.D. on Facebook.

Doctor (and former Danbury resident) fights cancer with rock ‘n’ roll, by Brian Koonz, The News-Times, Mar. 16, 2009.

UNC doctor-rockers score record deal, by Allen Mask, M.D., News Video Story, WRAL.com, Feb. 5, 2009 (CLICK HERE to watch video)

Medicine Meets Music: Surgeons Form Unusual Rock Band, by Gillian Granoff, Education Update Online, Feb. 2009.

Album will benefit gynecological cancer causes, by Sarah Avery – Staff Writer, The News & Observer, Jan. 30, 2009.

Band of Doctors, English, Music, Videos, Franz Strasser Blog, Dec. 17, 2008 (video news story).

Cancer doc rocks out, lands contract, tour next?, By Noelle Crombie, The Oregonian, KATU.com, Dec. 12, 2008.

Cancer docs form rock ‘n’ roll band and land a record deal, by Noelle Crombie, The Oregonian, Dec. 9, 2008 (story includes free MP3 clip of the N.E.D. song “False Pretenses”)

Doctors Double As Rock Stars To Help Raise Cancer Awareness, by Kafi Drexel, NY1 News, Dec. 9, 2008 (including video news story).

All hail the rock docs!, by Bill Egbert, Health Section, Daily News, December 8, 2008.

GynOncs Rock at Society Meetings, Band Looks Forward to Bigger & Better Gigs, While Raising Awareness of Women’s Cancers, by Margot J. Fromer, Oncology Times, Aug. 14, 2008. [PDF Document].

2008 State of the State of Gynecologic Cancers, Sixth Annual Report to the Women of America, Gynecologic Cancer Foundation. [PDF Document]

To Screen or Not To Screen? Ultrasound + CA125 Blood Test Fail to Detect Early Stage Ovarian Cancer

On March 10, 2009, Libby’s H*O*P*E*™ reported on the preliminary findings of a large British study that suggest that the combination of transvaginal ultrasound and CA125 blood test (a blood serum marker for ovarian cancer) can detect early ovarian cancer.  A recent U.S. study, published in the April 2009 issue of Obstetrics & Gynecology, found that the same combination screening regime did not detect early stage ovarian cancer and often resulted in unnecessary surgery. The U.S. and British studies, taken together, highlight the need to find an effective screening method to detect ovarian cancer.

On March 10, 2009, Libby’s H*O*P*E*™ reported on the preliminary findings of a large British study that suggest that the combination of transvaginal ultrasound and CA125 blood test (a blood serum marker for ovarian cancer) can detect early ovarian cancer.  A recent U.S. study, published in the April 2009 issue of Obstetrics & Gynecology, found that the same combination screening regime did not detect early stage ovarian cancer and often resulted in unnecessary surgery. The U.S. and British studies, taken together, highlight the need to find an effective screening method to detect ovarian cancer.

partridge-edward

Dr. Edward E. Partridge is the Director of the University of Alabama Birmingham Comprehensive Cancer Center, Birmingham, Alabama.

In a recent interview with U.S. News & World Report, the lead researcher of the U.S. study, Dr. Edward Partridge, Director of the University of Alabama Birmingham Comprehensive Cancer Center, said, “The jury is still out on the efficacy of screening with CA125 and transvaginal ultrasound in terms of reducing the mortality rate of ovarian cancer.  In this study, we do not have mortality data on the screening versus the non-screening group, so no conclusions can be made of the impact of screening with CA125 and transvaginal ultrasound.”

Partridge noted that this study only reports data on women who were screened. “We learned that the positive predictive value for the combination of tests is pretty low — in the 1 to 1.3 percent range,” he said. “A substantial number of the tests are false positives.”  In addition, screening with transvaginal ultrasound lead to a higher rate of surgery for positive findings than positive CA125, Partridge said. “Transvaginal ultrasound leads to more ‘unnecessary’ surgeries,” he said.  Partridge also noted that a high percentage of the cancers detected through screening were late-stage malignancies.  “If you detect them at a late stage, it is unlikely that you are going to impact mortality,” he said. “In order to affect mortality, one has to detect them at an earlier stage.”

As part of the study, the U.S. researchers collected data on 34,261 women who underwent annual screening for CA125 and also had transvaginal ultrasound.  A CA 125 value at or above 35 units/mL or an abnormality on transvaginal ultrasound was considered a “positive” screen.  The researchers found that  transvaginal ultrasound produced more positive findings for cancer than CA125 screening over the four years of screening, while the CA125 positive tests decreased from 60 percent in the first year to 34 percent in the third year.  Of the 89 invasive ovarian cancers diagnosed, 60 were detected through screening. In addition, 72 percent of the screen-detected cancer were late-stage cancers, the U.S. researchers reported.

Partridge told U.S. News & World Report that even detecting cancer early may not have an impact on mortality. “In any screening trial, the ultimate test of its usefulness is does it impact mortality,” he said.  Patridge added that based upon the findings of this study and The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) study published by Menon et. al. in the March 10 online edition of  The Lancet Oncology, the CA125 blood test & ultrasound screening method will not have any effect on mortality. “What we need is a more sensitive and specific screening test,” Partridge said.

In the UKCTOCS study, a British research team found that screening was able to identify most women with gynecologic cancer. The combination of the CA125 blood test and ultrasound found 90 percent of the cancers, while ultrasound alone found 75 percent of the cancers.  The researchers also found that almost 50 percent of all the cancers found were in an early stage (stage I or II).  And, 48 percent of the more invasive ovarian cancers detected were designated as being stage I tumors. By way of comparison, the British researchers pointed out that only 28 percent of ovarian cancers are identified in this early stage.

Dr. David G. Mutch, the Ira C. and Judith Gall Professor of Obstetrics and Gynecology at Washington University, St. Louis, and author of an accompanying journal editorial, agreed there is no worthwhile screening test for ovarian cancer as yet.  “Patients who were screened presented at the same stage as they would have if they were unscreened,” Mutch said. “There is no good screening test at this point.”  Mutch added that there is no reason to screen for ovarian cancer in the general population at this point. “The prevalence of the diseases is so low, one in 2,500, and the specificity of the tests are so low, that we are going to operate on a lot of patients unnecessarily,” he said.

Primary Sources: