U.S. President Barack Obama Proclaims September 2014 As National Ovarian Cancer Awareness Month — What Should You Know?

Today, U.S. President Barack Obama designated September 2014 as National Ovarian Cancer Awareness Month. “This month, our Nation stands with everyone who has been touched by this disease, and we recognize all those committed to advancing the fight against this cancer through research, advocacy, and quality care. Together, let us renew our commitment to reducing the impact of ovarian cancer and to a future free from cancer in all its forms.”

Today, U.S. President Barack Obama designated September 2014 as National Ovarian Cancer Awareness Month. The Presidential Proclamation is reproduced in full below.

During National Ovarian Cancer Awareness Month, Libby’s H*O*P*E*™ will continue to honor the women who have lost their lives to the disease (including our own Elizabeth “Libby” Remick), support those who are currently battling the disease, and celebrate with those who have beaten the disease. This month, medical doctors, research scientists, and ovarian cancer advocates renew their commitment to develop a reliable early screening test, improve current treatments, discover new groundbreaking therapies, and ultimately, defeat the most lethal gynecologic cancer.

Let us begin this month with several important facts relating to ovarian cancer. Please take time to review these facts — they may save your life or that of a loved one.

Ovarian Cancer Facts

Lethality. Ovarian cancer causes more deaths than any other cancer of the female reproductive system.

Statistics. In 2014, the American Cancer Society (ACS) estimates that there will be approximately 21,980 new ovarian cancer cases diagnosed in the U.S. ACS estimates that 14,270 U.S. women will die from the disease, or about 39 women per day or 1-to-2 women every hour. This loss of life is equivalent to 28 Boeing 747 jumbo jet crashes with no survivors — each and every year.

Signs & Symptoms. Ovarian cancer is not a “silent” disease; it is a “subtle” disease. Recent studies indicate that women with ovarian cancer are more like to experience four persistent, nonspecific symptoms as compared with women in the general population, 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. Note: Several other symptoms have been commonly reported by women with ovarian cancer. These symptoms include fatigue, indigestion, back pain, pain with intercourse, constipation and menstrual irregularities. However, these additional symptoms are not as useful in identifying ovarian cancer because they are also found in equal frequency in women within the general population who do not have the disease.

Age. Although the median age of a woman with ovarian cancer at initial diagnosis is 63, the disease cancer can afflict adolescent, young adult, and mature women. Ovarian cancer does not discriminate based upon age.

Prevention. Pregnancy, breastfeeding, long-term use of oral contraceptives, and tubal ligation reduce the risk of developing ovarian cancer.

Risk Factors.

• BRCA Gene Mutations. Women who have had breast cancer, or who have a family history of breast cancer or ovarian cancer may have increased risk. Women who test positive for inherited mutations in the BRCA-1 or BRCA-2 gene have an increased lifetime risk of breast and ovarian cancer. A women can inherit a mutated BRCA gene from her mother or father. Women of Ashkenazi (Eastern European) Jewish ancestry are at higher risk (1 out of 40) for inherited BRCA gene mutations. Studies suggest that preventive surgery to remove the ovaries and fallopian tubes in women possessing BRCA gene mutations can decrease the risk of ovarian cancer.

• Lynch Syndrome. An inherited genetic condition called “hereditary nonpolyposis colorectal cancer” (also called “Lynch syndrome“), which significantly increases the risk of colon/rectal cancer (and also increases the risk of other types of cancers such as endometrial (uterine), stomach, breast, small bowel (intestinal), pancreatic, urinary tract, liver, kidney, and bile duct cancers), also increases ovarian cancer risk.

• Hormone Therapy. The use of estrogen alone menopausal hormone therapy may increase ovarian cancer risk. The longer estrogen alone replacement therapy is used, the greater the risk may be. The increased risk is less certain for women taking both estrogen and progesterone, although a large 2009 Danish study involving over 900,000 women suggests that combination hormone therapy may increase risk. Because some health benefits have been identified with hormone replacement therapy, a women should seek her doctor’s advice regarding risk verses benefit based on her specific factual case.

• Smoking. Smoking has been linked to an increase in mucinous epithelial ovarian cancer.

Early Detection. 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 CA-125 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. This early detection strategy has shown promise in a 2013 University of Texas M.D. Anderson Cancer Center early detection study involving over 4,000 women. Importantly, another large ovarian cancer screening trial that is using similar early detection methods is under way in the United Kingdom, with results expected in 2015. The U.K. study is called “UKCTOCS” (UK Collaborative Trial of Ovarian Cancer Screening) and involves over 200,000 women aged 50-74 years.

Treatment.

• Treatment includes surgery and usually chemotherapy.

• Surgery usually includes removal of one or both ovaries and fallopian tubes (salpingo-oophorectomy), the uterus (hysterectomy), and the omentum (fatty tissue attached to some of the organs in the belly), along with biopsies of the peritoneum (lining of the abdominal cavity) and peritoneal cavity fluid.

• In younger women with very early stage tumors who wish to have children, removal of only the involved ovary and fallopian tube may be possible.

• Among patients with early ovarian cancer, complete surgical staging has been associated with better outcomes.

• For women with advanced disease, surgically removing all abdominal metastases larger than one centimeter (debulking) enhances the effect of chemotherapy and helps improve survival.

• For women with stage III ovarian cancer that has been optimally debulked, studies have shown that chemotherapy administered both intravenously and directly into the abdomen (intraperitoneally) improves survival.

• Studies have also found that ovarian cancer patients whose surgeries are performed by a board-certified gynecologic oncologist at a high quality/high surgical volume medical facility have more successful outcomes. Such medical facilities include National Cancer Institute-Designated Cancer Centers and member institutions of the National Comprehensive Cancer Network.

• Patients can enter clinical trials at the start of, during the course of, and even after, their ovarian cancer treatment(s).

• New types of treatment are being tested in ovarian and solid tumor clinical trials, including “biological therapy” and “targeted therapy.” For example, these types of treatment can exploit biological/molecular characteristics unique to an ovarian cancer patient’s specific tumor classification, or better “train” the patient’s own immune system to identify and attack her tumor cells, without harming normal cells.

Survival. 

• If diagnosed at the localized stage, the 5-year ovarian cancer survival rate is 92%; however, only about 15% of all cases are detected at an early stage, usually fortuitously during another medical procedure. The majority of cases (61%) are diagnosed at a distant or later stage of the disease.

• Overall, the 1-, 5-, and 10-year relative survival of ovarian cancer patients is 75%, 44%, and 34%, respectively.

• The 10-year relative survival rate for all disease stages combined is only 38%.

• Relative survival varies by age; women younger than 65 are twice as likely to survive 5 years (56%) following diagnosis as compared to women 65 and older (27%).

Help Spread the Word to “B-E-A-T” Ovarian Cancer

Please help us “B-E-A-T” ovarian cancer by spreading the word about the early warning signs & symptoms of the disease throughout the month of September.

B = bloating that is persistent and does not come and go

E = eating less and feeling fuller

A =abdominal or pelvic pain

T = trouble with urination (urgency or frequency)

Women who have these symptoms almost daily for more than a few weeks should see their doctor. Prompt medical evaluation may lead to detection at the earliest possible stage of the disease. As noted above, early stage diagnosis is associated with an improved prognosis.

__________________________________________________________

The White House

Office of the Press Secretary

For Immediate Release August 29, 2014

BY THE PRESIDENT OF THE UNITED STATES OF AMERICA

A PROCLAMATION

Ovarian cancer is the most deadly of all female reproductive system cancers. This year nearly 22,000 Americans will be diagnosed with this cancer, and more than 14,000 will die from it. The lives of mothers and daughters will be taken too soon, and the pain of this disease will touch too many families. During National Ovarian Cancer Awareness Month, we honor the loved ones we have lost to this disease and all those who battle it today, and we continue our work to improve care and raise awareness about ovarian cancer.

When ovarian cancer is found in its early stages, treatment is most effective and the chances for recovery are greatest. But ovarian cancer is difficult to detect early — there is no simple and reliable way to screen for this disease, symptoms are often not clear until later stages, and most women are diagnosed without being at high risk. That is why it is important for all women to pay attention to their bodies and know what is normal for them. Women who experience unexplained changes — including abdominal pain, pressure, and swelling — should talk with their health care provider. To learn more about the risk factors and symptoms of ovarian cancer, Americans can visit www.Cancer.gov.

Regular health checkups increase the chance of early detection, and the Affordable Care Act expands this critical care to millions of women. Insurance companies are now required to cover well-woman visits, which provide women an opportunity to talk with their health care provider, and insurers are prohibited from charging a copayment for this service.

For the thousands of women affected by ovarian cancer, the Affordable Care Act also prohibits insurance companies from denying coverage due to a pre-existing condition, such as cancer or a family history of cancer; prevents insurers from denying participation in an approved clinical trial for any life-threatening disease; and eliminates annual and lifetime dollar limits on coverage. And as we work to ease the burden of ovarian cancer for today’s patients, my Administration continues to invest in the critical research that will lead to earlier detection, improved care, and the medical breakthroughs of tomorrow.

Ovarian cancer and the hardship it brings have affected too many lives. This month, our Nation stands with everyone who has been touched by this disease, and we recognize all those committed to advancing the fight against this cancer through research, advocacy, and quality care. Together, let us renew our commitment to reducing the impact of ovarian cancer and to a future free from cancer in all its forms.

NOW, THEREFORE, I, BARACK OBAMA, President of the United States of America, by virtue of the authority vested in me by the Constitution and the laws of the United States, do hereby proclaim September 2014 as National Ovarian Cancer Awareness Month. I call upon citizens, government agencies, organizations, health care providers, and research institutions to raise ovarian cancer awareness and continue helping Americans live longer, healthier lives. I also urge women across our country to talk to their health care providers and learn more about this disease.

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

BARACK OBAMA

__________________________________________________________

Sources:

• Cancer Facts & Figures 2014. Atlanta: American Cancer Society; 2014 [PDF file].

• Presidential Proclamation — National Ovarian Cancer Awareness Month, 2013, Office of the Press Secretary, The White House, August 29, 2014.

U.S. President Barack Obama Proclaims September 2013 As National Ovarian Cancer Awareness Month — What Should You Know?

Yesterday, U.S. President Barack Obama designated September 2013 as National Ovarian Cancer Awareness Month. “… During National Ovarian Cancer Awareness Month, we lend our support to everyone touched by this disease, we remember those we have lost, and we strengthen our resolve to better prevent, detect, treat, and ultimately defeat ovarian cancer…. This month, we extend a hand to all women battling ovarian cancer. We pledge our support to them, to their families, and to the goal of defeating this disease. …”

Yesterday, U.S. President Barack Obama designated September 2013 as National Ovarian Cancer Awareness Month. The Presidential Proclamation is reproduced in full below.

During National Ovarian Cancer Awareness Month, Libby’s H*O*P*E*™ will honor the women who have lost their lives to the disease, support those who are currently battling the disease, and celebrate with those who have beaten the disease. This month, medical doctors, research scientists, and ovarian cancer advocates renew their commitment to develop a reliable early screening test, improve current treatments, discover new groundbreaking therapies, and ultimately, defeat the most lethal gynecologic cancer.

Let us begin this month with several important facts relating to ovarian cancer. Please take time to review these facts — they may save your life or that of a loved one.

Ovarian Cancer Facts

Lethality. Ovarian cancer causes more deaths than any other cancer of the female reproductive system.

Statistics. In 2013, the American Cancer Society (ACS) estimates that there will be approximately 22,240 new ovarian cancer cases diagnosed in the U.S. ACS estimates that 14,030 U.S. women will die from the disease, or about 38 women per day or 1-to-2 women every hour. This loss of life is equivalent to 28 Boeing 747 jumbo jet crashes with no survivors — every year.

Signs & Symptoms. Ovarian cancer is not a “silent” disease; it is a “subtle” disease. Recent studies indicate that women with ovarian cancer are more like to experience four persistent, nonspecific symptoms as compared with women in the general population, 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. Note: Several other symptoms have been commonly reported by women with ovarian cancer. These symptoms include fatigue, indigestion, back pain, pain with intercourse, constipation and menstrual irregularities. However, these additional symptoms are not as useful in identifying ovarian cancer because they are also found in equal frequency in women within the general population who do not have the disease.

Age. Although the median age of a woman with ovarian cancer at initial diagnosis is 63, the disease cancer can afflict adolescent, young adult, and mature women. Ovarian cancer does not discriminate based upon age.

Prevention. Pregnancy, breastfeeding, long-term use of oral contraceptives, and tubal ligation reduce the risk of developing ovarian cancer.

Risk Factors.

• BRCA Gene Mutations. Women who have had breast cancer, or who have a family history of breast cancer or ovarian cancer may have increased risk. Women who test positive for inherited mutations in the BRCA-1 or BRCA-2 gene have an increased lifetime risk of breast and ovarian cancer. A women can inherit a mutated BRCA gene from her mother or father. Women of Ashkenazi (Eastern European) Jewish ancestry are at higher risk (1 out of 40) for inherited BRCA gene mutations. Studies suggest that preventive surgery to remove the ovaries and fallopian tubes in women possessing BRCA gene mutations can decrease the risk of ovarian cancer.

• Lynch Syndrome. An inherited genetic condition called “hereditary nonpolyposis colorectal cancer” (also called “Lynch syndrome“), which significantly increases the risk of colon/rectal cancer (and also increases the risk of other types of cancers such as endometrial (uterine), stomach, breast, small bowel (intestinal), pancreatic, urinary tract, liver, kidney, and bile duct cancers), also increases ovarian cancer risk.

• Hormone Therapy. The use of estrogen alone menopausal hormone therapy may increase ovarian cancer risk. The longer estrogen alone replacement therapy is used, the greater the risk may be. The increased risk is less certain for women taking both estrogen and progesterone, although a large 2009 Danish study involving over 900,000 women suggests that combination hormone therapy may increase risk. Because some health benefits have been identified with hormone replacement therapy, a women should seek her doctor’s advice regarding risk verses benefit based on her specific factual case.

• Smoking. Smoking has been linked to an increase in mucinous epithelial ovarian cancer.

Early Detection. 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 CA-125 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. This early detection strategy has shown promise in a 2013 University of Texas M.D. Anderson Cancer Center early detection study involving over 4,000 women. Importantly, another large ovarian cancer screening trial that is using similar early detection methods is under way in the United Kingdom, with results expected in 2015. The U.K. study is called “UKCTOCS” (UK Collaborative Trial of Ovarian Cancer Screening) and involves over 200,000 women aged 50-74 years.

Treatment.

• Treatment includes surgery and usually chemotherapy.

• Surgery usually includes removal of one or both ovaries and fallopian tubes (salpingo-oophorectomy), the uterus (hysterectomy), and the omentum (fatty tissue attached to some of the organs in the belly), along with biopsies of the peritoneum (lining of the abdominal cavity) and peritoneal cavity fluid.

• In younger women with very early stage tumors who wish to have children, removal of only the involved ovary and fallopian tube may be possible.

• Among patients with early ovarian cancer, complete surgical staging has been associated with better outcomes.

• For women with advanced disease, surgically removing all abdominal metastases larger than one centimeter (debulking) enhances the effect of chemotherapy and helps improve survival.

• For women with stage III ovarian cancer that has been optimally debulked, studies have shown that chemotherapy administered both intravenously and directly into the abdomen (intraperitoneally) improves survival.

• Studies have also found that ovarian cancer patients whose surgeries are performed by a board-certified gynecologic oncologist at a high quality/high surgical volume medical facility have more successful outcomes. Such medical facilities include National Cancer Institute-Designated Cancer Centers and member institutions of the National Comprehensive Cancer Network.

• Patients can enter clinical trials at the start of, during the course of, and even after, their ovarian cancer treatment(s).

• New types of treatment are being tested in ovarian and solid tumor clinical trials, including “biological therapy” and “targeted therapy.” For example, these types of treatment can exploit biological/molecular characteristics unique to an ovarian cancer patient’s specific tumor classification, or better “train” the patient’s own immune system to identify and attack her tumor cells, without harming normal cells.

Survival. 

• If diagnosed at the localized stage, the 5-year ovarian cancer survival rate is 92%; however, only about 15% of all cases are detected at an early stage, usually fortuitously during another medical procedure. The majority of cases (61%) are diagnosed at a distant or later stage of the disease.

• Overall, the 1-, 5-, and 10-year relative survival of ovarian cancer patients is 75%, 44%, and 34%, respectively.

• The 10-year relative survival rate for all disease stages combined is only 38%.

• Relative survival varies by age; women younger than 65 are twice as likely to survive 5 years (56%) following diagnosis as compared to women 65 and older (27%).

Help Spread the Word To “B-E-A-T” Ovarian Cancer

Please help us “B-E-A-T” ovarian cancer by spreading the word about the early warning signs & symptoms of the disease throughout the month of September.

B = bloating that is persistent and does not come and go

E = eating less and feeling fuller

A =abdominal or pelvic pain

T = trouble with urination (urgency or frequency)

Women who have these symptoms almost daily for more than a few weeks should see their doctor. Prompt medical evaluation may lead to detection at the earliest possible stage of the disease. As noted above, early stage diagnosis is associated with an improved prognosis.

__________________________________________________________

The White House

Office of the Press Secretary

For Immediate Release August 30, 2013

BY THE PRESIDENT OF THE UNITED STATES OF AMERICA

A PROCLAMATION

Each September, America calls attention to a deadly disease that affects thousands of women across our country. This year, over 22,000 women will develop ovarian cancer, and more than half that number of women will die of this disease. During National Ovarian Cancer Awareness Month, we lend our support to everyone touched by this disease, we remember those we have lost, and we strengthen our resolve to better prevent, detect, treat, and ultimately defeat ovarian cancer.

Because ovarian cancer often goes undetected until advanced stages, increasing awareness of risk factors is critical to fighting this disease. Chances of developing ovarian cancer are greater in women who are middle-aged or older, women with a family history of breast or ovarian cancer, and those who have had certain types of cancer in the past. I encourage all women, especially those at increased risk, to talk to their doctors. For more information, visit www.Cancer.gov.

My Administration is investing in research to improve our understanding of ovarian cancer and develop better methods for diagnosis and treatment. As we continue to implement the Affordable Care Act, women with ovarian cancer will receive increased access to health care options, protections, and benefits. Thanks to this law, insurance companies can no longer set lifetime dollar limits on coverage or cancel coverage because of errors on paperwork. By 2014, the health care law will ban insurers from setting restrictive annual caps on benefits and from charging women higher rates simply because of their gender. Additionally, insurance companies will be prohibited from denying coverage or charging higher premiums to patients with pre-existing conditions, including ovarian cancer.

This month, we extend a hand to all women battling ovarian cancer. We pledge our support to them, to their families, and to the goal of defeating this disease.

NOW, THEREFORE, I, BARACK OBAMA, President of the United States of America, by virtue of the authority vested in me by the Constitution and the laws of the United States, do hereby proclaim September 2013 as National Ovarian Cancer Awareness Month. I call upon citizens, government agencies, organizations, health care providers, and research institutions to raise ovarian cancer awareness and continue helping Americans live longer, healthier lives. I also urge women across our country to talk to their health care providers and learn more about this disease.

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

BARACK OBAMA

__________________________________________________________

Sources:

• Cancer Facts & Figures 2013. Atlanta: American Cancer Society; 2013 [PDF file].

• Presidential Proclamation — National Ovarian Cancer Awareness Month, 2013, Office of the Press Secretary, The White House, August 30, 2013.

Ovarian Cancer Tumors Can Grow For Ten Years Or More Before Being Detected By Today’s Blood Tests

A new mathematical model developed by Stanford University School of Medicine scientists finds that ovarian cancer tumors can grow for 10 years or longer before currently available blood tests will detect them.

A new mathematical model developed by Stanford University School of Medicine scientists indicates that tumors can grow for 10 years or longer before currently available blood tests will detect them. The analysis, which was restricted to ovarian cancer tumors but is broadly applicable across all solid tumor types, was published online November 16 in Science Translational Medicine.

“The study’s results can be viewed as both bad and good news,” said Sanjiv “Sam” Gambhir, M.D., Ph.D., professor and chair of radiology and the study’s senior author. Sharon Hori, Ph.D., a postdoctoral scholar in Dr. Gambhir’s laboratory, is the lead study author.

The mathematical model developed by Dr. Sam Gambhir’s lab shows that it would be possible to detect tumors years before they grow big enough to metastasize if researchers can develop the right biomarkers.

The bad news, as explained by Dr. Gambhir, is that by time a tumor reaches a detectable size using today’s available blood tests, it is likely to have metastasized to other areas of the body, making it much more deadly than if it had been caught earlier. “The good news is that we have, potentially, 10 or even 20 years to find the tumor before it reaches this size, if only we can improve our blood-based methods of detecting tumors,” said Dr. Gambhir. “We think our mathematical model will help guide attempts to do that.”

The study advances previous research about the limits of current detection methods. For instance, it is strikingly consistent with a finding reported two years ago by Stanford biochemistry professor Patrick Brown, M.D., Ph.D., that current ovarian cancer tests could not detect tumors early enough to make a significant dent in the mortality rate. There is a push to develop more-sensitive diagnostic tests and find better biomarkers, and Dr. Gambhir’s new model could be an essential tool in this effort. For the first time, the new model connects the size of a tumor with blood biomarker levels being shed by that tumor.

To create their model, Drs. Gambhir and Hori used mathematical models originally developed to predict the concentration of drugs injected into the blood. The investigators linked these to additional models of tumor cell growth.

Tumors do not secrete drugs, but they can shed telltale molecules into surrounding tissue, from which those substances, known as “biomarkers,” diffuse into the blood. Some biomarkers may be made predominantly by tumor cells.  These substances can be measured in the blood as proxies for a tumor.

Some biomarkers are in wide use today. One is the well-known PSA (prostate specific antigen) for prostate cancer. Another example of a biomarker is CA-125 (cancer antigen 125) for ovarian cancer. But these and other currently used blood tests for cancer biomarkers were not specifically developed for early detection, and are generally more effective for relatively noninvasive monitoring of the progress of a late-stage tumor or tumor response to treatment. That is, rising blood levels of the substance may indicate that the tumor is growing, while declining levels may indicate possible tumor shrinkage.

Both CA-125 and PSA are also produced, albeit in smaller amounts, by healthy tissue, complicating efforts to detect cancer at an early stage when the tumor’s output of the biomarker is relatively low.

The new mathematical model employs separate equations, each governing the movement of a biomarker from one compartment into the next. Into these equations, one can plug known values — such as how fast a particular type of tumor grows, how much of the biomarker a tumor cell of this type sheds per hour, and the minimum levels of the biomarker that must be present in the blood for a currently available assay to detect it.

As a test case, Drs. Gambhir and Hori chose CA-125, a well-studied biomarker which is shed into the blood by ovarian cancer tumors. Ovarian cancer is a notorious example of a condition for which early detection would make a significant difference in survival outcomes.

CA-125 is a protein made almost exclusively by ovarian tumor cells. The well-known pharmacokinetics, metabolic fates (typical amounts secreted by an ovarian cell), typical ovarian tumor growth rates, and other properties of CA-125 make the biomarker an excellent candidate for “road testing” with Gambhir and Hori’s model. CA-125 is by no means the ideal biomarker, said Dr. Gambhir, while noting that it can still be used to better understand the ideal properties of biomarkers for early ovarian cancer detection.

Applying their equations to CA-125, Drs. Gambhir and Hori determined that an ovarian cancer tumor would need to reach a size of approximately 1.7 billion cells, or the volume of a cube with a 2-centimeter edge, before the currently available CA-125 blood test could reliably detect it. At typical tumor-growth rates, it would take a single cancer cell approximately 10.1 to 12.6 years of development to become a tumor containing 1.7 billion cells.

The model further calculated that a biomarker otherwise equivalent to CA125 — but shed only by ovarian tumor cells — would allow reliable detection within 7.7 years, while the tumor’s size would be that of a tiny cube about one-sixth of an inch high.

In the last decade, many potential new biomarkers for different forms of cancers have been identified. There’s no shortage of promising candidates — six for lung cancer alone, for example. But validating a biomarker in large clinical trials is a long, expensive process. So it is imperative to determine as efficiently as possible which, among many potential tumor biomarkers, is the best prospective candidate.

“This [mathematical] model could take some of the guesswork out of it,” Gambhir said. He also stated:

“It [the mathematical model] can be applied to all kinds of solid cancers and prospective biomarkers as long as we have enough data on, for instance, how much of it a tumor cell secretes per hour, how long the biomarker can circulate before it’s degraded and how quickly tumor cells divide. We can tweak one or another variable — for instance, whether a biomarker is also made in healthy tissues or just the tumor, or assume we could manage to boost the sensitivity of our blood tests by 10-fold or 100-fold — and see how much it advances our ability to detect the tumor earlier on.”

There are new detection technologies capable of detecting biomarkers at concentrations as low as a few hundred molecules per milliliter (1-cubic centimeter) of blood. In 2009, Dr. Gambhir and his colleagues reported on one such developing technology: “magneto-nanosensors” that can detect biomarkers with a 100-fold greater sensitivity than current methods.

Better biomarker detection alone might allow ovarian cancer tumor detection at the 9-year point, said Gambhir.

A second priority is to come up with new and better biomarkers. “It’s really important for us to find biomarkers that are made exclusively by tumor cells,” Dr. Gambhir said.

Under the right conditions (a highly sensitive assay measuring levels of a biomarker that is shed only by cancer cells), Gambhir stated, the model predicts that a tiny tumor with a volume equivalent to a cube less than one-fifteenth of an inch (or 1.7 millimeters) on a side could be detected.

Dr. Gambhir is also the Virginia and D.K. Ludwig Professor in Cancer Research and director of the Molecular Imaging Program at Stanford, the director of the Canary Center at Stanford for Cancer Early Detection, and a member of the Stanford Cancer Institute.

The study was funded by the Canary Foundation and the National Cancer Institute.

Sources:

• Hori S, Gambhir S, Mathematical Model Identifies Blood Biomarker–Based Early Cancer Detection Strategies and Limitations. Sci. Transl. Med. 3, 109ra116 (2011).

• New model establishes guidelines for earlier cancer detection, Press Release, Stanford School of Medicine, November 16, 2011.

Mesothelin Antibodies Occur In Some Women With An Epidemiologic Risk For Ovarian Cancer.

Researchers at Rush University Medical Center discover mesothelin antibodies in the bloodstream of infertile women, who possess a higher risk of ovarian cancer.

Using a new approach to developing biomarkers for the very early detection of ovarian cancer, researchers at Rush University Medical Center have identified a molecule in the bloodstream of infertile women, who possess a higher risk of ovarian cancer. This finding may be relevant in the future for screening women at high risk for the disease — or even those with early-stage ovarian cancer.

The molecule — an antibody that the human body manufactures — is an autoimmune response to mesothelin. Mesothelin a well-characterized ovarian cancer antigen and protein which is found in abundance on the surface of ovarian cancer cells, but present only in limited amounts in normal human tissue.

The study is published in the August 16 online version issue of Cancer Epidemiology, Biomarkers & Prevention, published by the American Association for Cancer Research (AACR).

Judith Luborsky, Ph.D., Lead Study Author; Professor, Pharmacology, Obstetrics & Gynecology and Preventive Medicine, Rush Medical College

“The finding is extremely important because at present medical tests are unable to detect ovarian cancer in its early stages, which is why death rates from this disease are so high,” said Judith Luborsky, Ph.D., professor of pharmacology, obstetrics and gynecology and preventive medicine at Rush and the lead author of the study.

“Our approach to discovering cancer biomarkers was unique in this study. Instead of investigating molecules specific to ovarian cancer alone, we asked what molecules women with a risk of ovarian cancer and those with ovarian cancer had in common,” Luborsky said.

The study may have enabled the researchers to explain, in part, the link between infertility and ovarian cancer that has been established in numerous epidemiological surveys.

“More important, with the discovery of the mesothelin antibody, we now have what appears to be a biomarker that can potentially be used in screening tests to help us conquer ovarian cancer,” Luborsky said.

According to the American Cancer Society’s most recent estimates, it is anticipated that 21,900 new cases of ovarian cancer will be diagnosed in the U.S. in 2011, and approximately 15,460 deaths will occur in connection with the disease. Ovarian cancer is the ninth most common cancer in women (not counting skin cancer) and ranks as the fifth highest cause of cancer death in women. It is the most lethal gynecologic cancer. The poor prognosis for women with ovarian cancer is due to the lack of both clinical symptoms when the cancer first develops and the absence of laboratory tests specific to the disease.

In the study at Rush, researchers tested for mesothelin antibodies in the bloodstream of 109 women who were infertile; 28 women diagnosed with ovarian cancer, 24 women with benign ovarian tumors or cysts, and 152 healthy women. Causes of infertility included endometriosis, ovulatory dysfunction, and premature ovarian failure. Some causes of infertility were unexplained.

Significant levels of mesothelin antibodies were found in women with premature ovarian failure, ovulatory dysfunction and unexplained infertility, as well as in women with ovarian cancer. The same results were not found in women with endometriosis, good health, or benign disease. Endometriosis is generally associated with the clear cell and endometrioid subtypes of epithelial ovarian cancer, as compared to other forms of the disease associated with infertility, which may explain why mesothelin antibodies were not found in the endometriosis cases.

It is important to emphasize that the explanation as to why the presence of mesothelin antibodies in the bloodstream should be linked with ovarian cancer is not clear.

“It has been hypothesized that an autoimmune response precedes or somehow contributes to the development and progression of malignant tumors,” Luborsky said. “We think that antibodies may arise in response to very early abnormal changes in ovarian tissue that may or may not progress to malignancy, depending on additional triggering events. Or, alternatively, antibodies may bind to normal cells in the ovary, causing dysfunction and leading to infertility — and, in a subpopulation of women, to the development of ovarian cancer.”

Other researchers involved in the study were Yi Yu, MS, and Seby Edassery, MS, both from Rush, as well as a group led by Ingegerd Hellstrom, M.D., Ph.D., and Karl Eric Hellstrom, M.D., Ph.D., which included Yuan Yee Yip, BS, Jade Jaffar, BS, and Pu Liu, Ph.D. from Harborview Medical Center at the University of Washington.

The study was supported by funding from the National Institutes of Health and Fujirebio Diagnostics, Inc.

About Rush

Rush is a not-for-profit academic medical center comprising Rush University Medical Center, Rush University, Rush Oak Park Hospital and Rush Health.

Rush’s mission is to provide the best possible care for its patients. Educating tomorrow’s health care professional, researching new and more advanced treatment options, transforming its facilities and investing in new technologies—all are undertaken with the drive to improve patient care now, and for the future.

Sources:

• Luborsky JL, et al. Autoantibodies to Mesothelin in Infertility. Cancer Epidemiol Biomarkers Prev. 2011 Aug 16. PubMed PMID: 21846819 [Epub ahead of print]

• Researchers at Rush University Medical Center Discover Antibody That May Help Detect Ovarian Cancer in its Earliest Stages, News Release, Rush University Medical Center, August 16, 2010.

2011 ASCO: Screening With CA-125 & Transvaginal Ultrasound Does Not Reduce Ovarian Cancer Death Rate, Results in High Number of False Positives

Findings from a large, long-term study – the Prostate, Lung, Colorectal and Ovarian (PLCO) Screening Trial – showed that using a CA-125 blood test and transvaginal ultrasound for early detection of ovarian cancer did not reduce the risk of dying from the disease, and resulted in a large number of false positives and related follow-up procedures.

ASCO Releases Studies From Upcoming Annual Meeting – Important Advances in Targeted Therapies, Screening, and Personalized Medicine

The American Society of Clinical Oncology (ASCO) today highlighted several studies in a press briefing from among more than 4,000 abstracts publicly posted online at http://www.asco.org in advance of ASCO’s 47th Annual Meeting. An additional 17 plenary, late-breaking and other major studies will be released in on-site press conferences at the Annual Meeting.

The meeting, which is expected to draw approximately 30,000 cancer specialists, will be held June 3-7, 2011, at McCormick Place in Chicago, Ill. The theme of this year’s meeting is “Patients. Pathways. Progress.”

“This year marks the 40th anniversary of the signing of the National Cancer Act, a law that led to major new investments in cancer research. Every day in our offices, and every year at the ASCO meeting, we see the results of those investments. People with cancer are living longer, with a better quality of life, than ever before,” said George W. Sledge Jr., M.D., President of ASCO, Ballve-Lantero Professor of Oncology and professor of pathology and laboratory medicine at the Indiana University School of Medicine.

“With our growing understanding of the nature of cancer development and behavior, cancer is becoming a chronic disease that a growing number of patients can live with for many years,” said Dr. Sledge. “The studies released today are the latest examples of progress against the disease, from new personalized treatments, to new approaches to screening and prevention.”

The study results from a large clinical trial involving ovarian cancer screening were highlighted in today’s press briefing as summarized below.

Screening with CA-125 and Transvaginal Ultrasound Does Not Reduce Ovarian Cancer Death Rate, Results in High Number of False Positives

A randomized, multicenter screening study of nearly 80,000 women in the general population showed that using a CA-125 blood test and transvaginal ultrasound for early detection of ovarian cancer did not reduce the risk of dying from the disease, and resulted in a large number of false positives and related biopsies and follow-up procedures. The results indicate that while these tests are widely and appropriately used to evaluate symptoms, and to gauge disease status and effectiveness of treatment in women already diagnosed with ovarian cancer, they are not useful in screening the general population.

Saundra S. Buys, M.D., Medical Director, Huntsman Cancer Institute’s High Risk Breast Cancer Clinic; Professor, Depart. of Internal Medicine, Univ. of Utah School of Medicine

“There hasn’t been a good method for the early detection of ovarian cancer, and our hypothesis was that CA-125 and transvaginal ultrasound, which are useful in measuring disease, would also identify ovarian cancer early, at a stage in which it is more likely to be cured,” said lead author Saundra Buys, M.D., professor of medicine at the University of Utah and Huntsman Cancer Institute in Salt Lake City. “The results were disappointing, but not necessarily surprising. The study shows that the available tests are not effective and may actually cause harm because of the high number of false positives. These results point to the continued need for more precise and effective screening tools for this disease.”

In the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, 78,216 women ages 55 to 74 were assigned to either annual screening (39,105 women) or usual care (39,111 women) between 1993 and 2001. Women in the screening arm were offered annual CA-125 testing for six years and transvaginal ultrasound for four, and followed for up to 13 years. Those in the usual care arm were not offered the screening tests.

The results showed no statistically significant difference in ovarian cancer cases or mortality between the two arms. Ovarian cancer was diagnosed in 212 women in the screening group arm compared to 176 in the usual care arm; 118 women in the screening arm died from ovarian cancer, while 100 died from ovarian cancer in the usual care group.

Among women in the screening arm, there were a high number of false positives – 3,285 false positives, compared to just 212 true positives. Of women who had a false positive test, 1,080 underwent surgery for biopsy – the procedure generally required to evaluate positive test results; 163 of them had serious complications.

The authors emphasized that the study results don’t apply to screening women with symptoms or abnormal findings on physical examination. [emphasis added] Physical examination based on symptoms and appropriate follow-up testing remains the best available approach for ovarian cancer detection.

[Note: This summary contains updated data and a correction from the original abstract. Correction:  Of the 3,285 women who received a false positive exam, 1,080 underwent surgery. Of those surgical patients, 163 encountered at least one serious complication.]

Sources:

• ASCO Releases Studies From Upcoming Annual Meeting – Important Advances in Targeted Therapies, Screening, and Personalized Medicine – Screening with CA-125 and Transvaginal Ultrasound Does Not Reduce Ovarian Cancer Death Rate, Results in High Number of False Positives, Press Release, American Society of Clinical Oncology, May 18, 2011. [Adobe Reader PDF]

• Buys SS, Partridge E, Black A, et. al. Effect of screening on ovarian cancer mortality in the prostate, lung, colorectal and ovarian (PLCO) cancer randomized screening trial. J Clin Oncol 29: 2011 (suppl; abstr 5001)(2011 ASCO Annual Meeting).

Resources:

• Screening Does Not Reduce Deaths from Ovarian Cancer for the General Population, http://www.Cancer.net, May 18, 2011.

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.

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:

• Fox Chase Researchers Identify Early Ovarian Cancers -Discovery May Facilitate Development of Screening Test, News Release, Fox Chase Cancer Center, April 26, 2010.

• Pothuri B, Leitao MM, Levine DA, Viale A, Olshen AB, et al. 2010 Genetic Analysis of the Early Natural History of Epithelial Ovarian Carcinoma. PLoS ONE 5(4): e10358. doi:10.1371/journal.pone.0010358

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.

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

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, 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, 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:

• Research Team Designing Holographic Imaging System for Ovarian Cancer, by Rebecca Ruiz-McGill, UA News, University of Arizona,  10 Aug. 2009.

• Hariri LP, Bonnema GT, Schmidt K, et. al. Laparoscopic optical coherence tomography imaging of human ovarian cancer. Gynecol Oncol. 2009 Aug;114(2):188-94. Epub 2009 May 29. PubMed PMID: 19481241.

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)

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 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].

Senators Kennedy & Hutchison Renew War On Cancer

On March 26, 2009, Senators Edward M. Kennedy (D-Massachusetts) and Kay Bailey Hutchison (R-Texas) introduced the 21st Century Cancer Access to Life-Saving Early detection, Research and Treatment (ALERT) Act, a bill to comprehensively address the challenges our nation faces in battling cancer. This is the first sweeping cancer legislation introduced since the National Cancer Act in 1971, authored by Senator Kennedy. The 21^st Century Cancer ALERT Act is a comprehensive approach to cancer prevention and detection, research and treatment. It invests in cancer research infrastructure and improves collaboration among existing efforts. Prevention and early detection for those most at risk are emphasized through support for innovative initiatives and new technologies such as biomarkers.  The legislation addresses the need to increase enrollment in clinical research by increasing access and removing barriers to patients’ participation in clinical trials. The bill also includes a plan designed to improve care for cancer survivors. Additional provisions regarding prevention and screening initiatives will increase access to care for underserved populations and reduce the burden of disease and cost of healthcare to the nation.

Edward M. Kennedy, U.S. Senator For The Commonwealth of Massachusetts

On March 26, 2009, Senators Edward M. Kennedy (D-Massachusetts) and Kay Bailey Hutchison (R-Texas) introduced the 21st Century Cancer Access to Life-Saving Early detection, Research and Treatment (ALERT) Act, a bill to comprehensively address the challenges our nation faces in battling cancer. This is the first sweeping cancer legislation introduced since the National Cancer Act in 1971, authored by Senator Kennedy. The 21^st Century Cancer ALERT Act is a comprehensive approach to cancer prevention and detection, research and treatment. It invests in cancer research infrastructure and improves collaboration among existing efforts. Prevention and early detection for those most at risk are emphasized through support for innovative initiatives and new technologies such as biomarkers.  The legislation addresses the need to increase enrollment in clinical research by increasing access and removing barriers to patients’ participation in clinical trials. The bill also includes a plan designed to improve care for cancer survivors. Additional provisions regarding prevention and screening initiatives will increase access to care for underserved populations and reduce the burden of disease and cost of healthcare to the nation.

We provide below the full text of the following documents:

• Kennedy On The Introduction of the 21st Century ALERT Act, As Entered Into the Congressional Record, Office of Senator Edward M. Kennedy, U.S. Senator For Massachusetts, March 26, 2009.

• Kennedy Renews the War Against Cancer, Press Release, Office of Senator Edward M. Kennedy, U.S. Senator For Massachusetts, March 26, 2009.

• 21st Century Cancer ALERT Act, Senators Kennedy and Hutchinson, Section by Section Summary, Office of Senator Edward M. Kennedy, U.S. Senator For Massachusetts, March 26, 2009.

• Renewing the War on Cancer, by Edward M. Kennedy and Kay Bailey Hutchinson, Op-Ed., Houston Chronicle, March 26, 2009.

• S. 717: 21st Century Cancer ALERT (Access to Life-Saving Early detection, Research and Treatment) Act, 111th Congress,www.govtrack.us (Full text of bill as of April 13, 2009).  CLICK HERE for Adobe Reader PDF document.

_____________________________________________________

KENNEDY ON THE INTRODUCTION OF THE 21st Century ALERT Act

As Entered into the [Congressional] Record

March 26, 2009

FOR IMMEDIATE RELEASE

Thirty seven years ago, a Republican President and Democratic Congress came together in a new commitment to find a cure for cancer. At the time, a cancer diagnosis meant almost certain death. In 1971, we took action against this deadly disease and passed the National Cancer Act with broad bipartisan support, and it marked the beginning of the War on Cancer.

Since then, significant progress has been made. Amazing scientific research has led to methods to prevent cancer, and treatments that give us more beneficial and humane ways to deal with the illness. The discoveries of basic research, the use of large scale clinical trials, the development of new drugs, and the special focus on prevention and early detection have led to breakthroughs unimaginable only a generation ago.

As a result, cancer today is no longer the automatic death sentence that it was when the war began. But despite the advances we have made against cancer, other changes such as aging of the population, emerging environmental issues, and unhealthy behavior, have allowed cancer to persist. The lives of vast numbers of Americans have been touched by the disease. In 2008, over 1.4 million Americans were diagnosed with some form of cancer, and more than half a million lost their lives to the disease.

The solution isn’t easy but there are steps we can and must take now, if we hope to see the diagnosis rate decline substantially and the survival rate increase in the years ahead. The immediate challenge we face is to reduce the barriers that obstruct progress in cancer research and treatment by integrating our current fragmented and piecemeal system of addressing the disease.

Last year, my colleague Senator Hutchison and I agreed that to build on what the nation has accomplished, we must launch a new and more urgent war on cancer. The 21st Century Cancer ALERT Act we are introducing today will accelerate our progress by using a better approach to fighting this relentless disease. Our goal is to break down the many barriers that impede cancer research and prevent patients from obtaining the treatment that can save their lives.

We must do more to prevent cancer, by emphasizing scientifically proven methods such as tobacco cessation, healthy eating, and exercise. Healthy families and communities that have access to nutritious foods and high quality preventive health care will be our best defense against the disease. I’m confident that swift action on national health reform will make our vision of a healthier nation a reality. Obviously, we cannot prevent all cancers, so it is also essential that the cancers that do arise be diagnosed at an initial, curable stage, with all Americans receiving the best possible care to achieve that goal.

We cannot overemphasize the value of the rigorous scientific efforts that have produced the progress we have made so far. To enhance these efforts, our bill invests in two key aspects of cancer research– infrastructure and collaboration of the researchers. We include programs that will bring resources to the types of cancer we least understand. We invest in scientists who are committed to translating basic research into clinical practice, so that new knowledge will be brought to the patients who will most benefit from it.

One of the most promising new breakthroughs is in identifying and monitoring the biomarkers that leave enough evidence in the body to alert clinicians to subtle signs that cancer may be developing. Biomarkers are the new frontier for improving the lives of cancer patients because they can lead to the earliest possible detection of cancer, and the Cancer ALERT Act will support the development of this revolutionary biomarker technology.

In addition, we give new focus to clinical trials, which have been the cornerstones of our progress in treating cancer in recent decades. Only through clinical trials are we able to discover which treatments truly work. Today, however, less than 5% of cancer patients currently are enrolled in clinical trials, because of the many barriers exist that prevent both providers and patients from participating in these trials. A primary goal of our bill is to begin removing these barriers and expanding access to clinical trials for many more patients.

Further, since many cancer survivors are now living longer lives, our health systems must be able to accommodate these men and women who are successfully fighting against this deadly disease. It’s imperative for health professionals to have the support they need to care for these survivors. To bring good lifelong care to cancer survivors, we must invest more in research to understand the later effects of cancer and how treatments affect survivors’ health and the quality of their lives.

We stand today on the threshold of unprecedented new advances in this era of extraordinary discoveries in the life sciences, especially in personalized medicine, early diagnosis of cancer at the molecular level, and astonishing new treatments based on a patient’s own DNA. To make the remarkable promise of this new era a reality, we must make sure that patients can take DNA tests, free of the fear that their genetic information will somehow be used to discriminate against them. We took a major step toward unlocking the potential of this new era by approving strong protections against genetic discrimination in health insurance and employment when the Genetic Nondiscrimination Act was signed into law last year.

In sum, we need a new model for research, prevention and treatment of cancer, and we are here today to start that debate in Congress. We must move from a magic bullet approach to a broad mosaic of care, in which survivorship is also a key part of our approach to cancer. By doing so, we can take a giant step toward reducing or even eliminating the burden of cancer in our nation and the world. It’s no longer an impossible dream, but a real possibility for the future.

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Press Contact

Anthony Coley/ Melissa Wagoner (202) 224-2633

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Kennedy Renews the War Against Cancer

March 26, 2009

FOR IMMEDIATE RELEASE

Bill will Renew America’s Commitment to Fighting Cancer and Finding Cures

WASHINGTON, DC— Senators Edward M. Kennedy and Kay Bailey Hutchison today introduced the 21st Century Cancer Access to Life-Saving Early detection, Research and Treatment (ALERT) Act, a bill to comprehensively address the challenges our nation faces in battling this disease. This is the first sweeping cancer legislation introduced since the National Cancer Act in 1971, authored by Kennedy.

The 21st Century Cancer ALERT Act will provide critical funding for promising research in early detection, and supply grants for screening and referrals for treatment. These measures will also ensure patient access to prevention and early detection, which is supplemented by increased access to clinical trials and information.

The bill places an emphasis on strengthening cancer research and the urgent need for resources to both prevent and detect cancers at an early stage. The bill strives to give scientists the tools they need to fight cancer and to understand more thoroughly how the disease works. Through fostering new treatments, increased preventative measures and funding for research, the ALERT Act begins a new chapter in how Americans will live with and fight cancer.

Senators Kennedy and Hutchison first proposed the idea for comprehensive cancer legislation last May, when the Health, Education, Labor and Pensions Committee held a hearing to discuss the need for a renewed focus on the deadly disease. Elizabeth Edwards, Lance Armstrong and Hala Moddelmog from Susan G. Komen for the Cure testified at the hearing.

Senator Kennedy, Chairman of the Health, Education, Labor, and Pensions Committee, said, “We’ve come a long way in fighting cancer since we passed the National Cancer Act thirty-eight years ago, but not far enough. Americans still live in fear that they or someone they love will be affected. Today, we’re better equipped for the fight— learning each and every day a little bit more about the disease and what we can do to fight it. Cancer is a complex disease and it requires comprehensive strategies to fight it— strategies that integrate research, prevention and treatment. This bill will renew our efforts to make progress in the battle against cancer, and to give patients and their families a renewed sense of hope.”

“Our nation declared the War on Cancer in 1971, yet, nearly 38 years later, cancer is expected to become the leading killer of Americans. We must bring renewed focus and vigor to this fight.” said Senator Hutchison. “The prescription isn’t simple, but there are steps we must take if we are going to see the cancer diagnosis rate decline, while raising the prognosis for survival among those who do have the disease. Our legislation will enact those necessary steps so we may see more progress and coordination in cancer research and treatment.”

“We know how to lengthen and improve the lives of people with cancer, but we’ve chosen as a nation to turn our backs on some of us who have the disease,” said Elizabeth Edwards. “I urge the United States Senate to embrace the ALERT Act and get it to the President’s desk as soon as possible.”

“In 2010, cancer is expected to be the leading cause of death worldwide. Every American is touched by this disease,” said Lance Armstrong, chairman and founder of the Lance Armstrong Foundation. “The 21st Century Cancer ALERT Act and its authors’ leadership in reforming our nation’s approach to the war on cancer are a very welcome step forward to every member of the LIVESTRONG movement.”

“It’s been 38 years since our nation first declared war on cancer, and yet we are still facing a significant cancer crisis.  The Kennedy-Hutchison Cancer ALERT Act will reignite the war on cancer,” said Nancy G. Brinker, founder of Susan G. Komen for the Cure.  “We must all work together and let nothing stand in the way of discovering and delivering the cures to cancer.”

Senate action on this bill is expected this Congressional session.

A section-by-section summary of the legislation is below as well as an op-ed authored by Senators Hutchison and Kennedy that appeared this morning in the Houston Chronicle and on the Boston Globe’s website.

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21^st Century Cancer ALERT Act

Senators Kennedy and Hutchison

Section by Section Summary

The 21^st Century Cancer ALERT Act is a comprehensive approach to cancer prevention and detection, research and treatment. It invests in cancer research infrastructure and improves collaboration among existing efforts. Prevention and early detection for those most at risk are emphasized through support for innovative initiatives and new technologies such as biomarkers.  The legislation addresses the need to increase enrollment in clinical research by increasing access and removing barriers to patients’ participation in clinical trials. The bill also includes a plan designed to improve care for cancer survivors. Additional provisions regarding prevention and screening initiatives will increase access to care for underserved populations and reduce the burden of disease and cost of healthcare to the nation.

Section 1 and 2 – Findings and Declaration of Purpose

Section 3- Advancement of the National Cancer Program (NCP)

Modernize the role of the National Cancer Institute (NCI) in coordinating the NCP

• Identifies relevant federal agencies to coordinate with NCI
• Improves the annual budget estimate for the NCP by including the needs of the entire NCP and submitting the budget annually to House and Senate Budget and Appropriations Committees
• Increases participation of other federal agencies in the National Cancer Advisory Board
• Encourages early detection and translational research opportunities

Biological Resource Coordination and Advancement of Technologies for Cancer Research

• Establishes an entity within NCI to support an interconnected network of biorepositories with consistent, interoperable systems for collection, storage, annotation, and information sharing
• Facilitates research by linking cancer registries to other federal data sources including those at Centers for Medicare and Medicaid Services [CMS], Social Security Administration, and Centers for Disease Control and Prevention
• Requires hospitals and ambulatory care centers that receive federal funds to offer patients the opportunity to contribute their biospecimens and clinical data to a clinical registry

Section 4 – Comprehensive and Responsible Access to Research, Data, and Outcomes

• Calls for guidance from the Office of Human Research Protection on the use of a centralized Institutional Review Board
• Improves privacy standards in clinical research by clarifying when de-identified patient information may be disclosed
• Calls for HHS to study the advantages and disadvantages of the synchronization of the standards for research under the Common Rule and the Privacy Rule
• Clarifies the application of the Privacy Rule to external researchers

Section 5- Enhanced Focus and Reporting on Cancer Research

• Calls for NCI to report annually on plans and progress regarding research on cancers with low incidence and low survival rates
• Establishes grants program to conduct research on cancers with low incidence and low survival rates

Section 6 – Continuing Access to Care for Prevention and Early Detection

Screening and Early Detection

• Establishes a grant program to states for colorectal cancer screening and referrals for medical treatment (similar to the national breast and cervical cancer early detection program). States are given the option to cover screened persons found to have cancer under Medicaid.

Cancer Prevention

• Authorizes grants for a medical mobile van program to conduct cancer screening and prevention education activities in communities that are underserved and suffer from barriers to preventative cancer care

Access to Prevention and Early Detection for Certain Cancers

• Calls for the Secretary to include cancers with especially low survival rates in the Cancer Genome Atlas Consortium
• Calls for the Secretary to establish formal working groups for cancers with especially low survival rates in the Early Detection Research Network
• Calls for the National Institute of Biomedical Imaging and Bioengineering to ensure that the Quantum Grant program and the Image Guided Interventions program expedite the development of interventions for cancers with low survival rates

Section 7– Early Recognition and Treatment of Cancer Through the Use of Biomarkers

Promote the Discovery and Development of Biomarkers

• Establishes and coordinates federal agencies to establish a highly directed, contract based program that will support the development of innovative biomarker discovery technologies
• Calls for FDA and CMS to work together to create guidelines for clinical study designs that will enable sponsors to generate clinical data that will be adequate for review by both agencies
• Conducts a demonstration project to provide limited regional coverage for biomarker tests and establish procedures for independent research entities to conduct high quality assessments of the efficacy and cost effectiveness of biomarker tests

Section 8: National Cancer Coverage Guidelines

Ensure Patient Access to Clinical Trials

• Facilitates expanded access to clinical trials by requiring ERISA governed health plans to continue to provide coverage of routine care regardless of whether a patient enrolls in a clinical trial

Section 9: Health Professions Workforce

Ensure a Stable Workforce for the Future

• Supports retired nurse military officers to work as nurse faculty
• Directs Secretary of Health and Human Services to identify oncology workforce gaps

Section 10: Patient Navigator Program

Improve Upon Existing Patient Navigator Programs

• Ensures that patient navigators meet minimum core proficiencies
• Reauthorizes the Patient Navigator program through 2015

Section 11: Cancer Care and Coverage Under Medicaid and Medicare

Improvements in Coverage of Cancer Services

• Codifies current Medicare policy to reimburse for routine care while patients are enrolled in clinical trials
• Conducts a demonstration project to evaluate the cost, effectiveness, and potential savings to Medicare of reimbursing providers for comprehensive cancer care planning services to the Medicare population
• Directs states to offer tobacco cessation medications and counseling to pregnant women enrolled in Medicaid

Section 12: Cancer Survivorship and Complete Recovery Initiatives

Childhood Cancers

• Establishes priority areas for NIH activities related to childhood cancer survivorship
• Authorizes grants for research on the causes of health disparities in childhood cancer survivorship and to evaluate follow up care for childhood cancer survivors

Complete Recovery Care

• Defines “complete recovery care” which includes care to address secondary effects of cancer and its treatment, including late and psychosocial effects
• Coordinates complete recovery care activities across federal agencies
• Establishes a Collaborative that will develop a plan for workforce development for complete recovery care

Section 13: Activities of the Food and Drug Administration

Sense of the Senate

• Encourages the FDA to harmonize policies to facilitate the development of drugs; explore clinical trial endpoints; and, modernize the Office of Oncology Drug Products

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Renewing the War on Cancer

By Edward M. Kennedy and Kay Bailey Hutchison

Kay Bailey Hutchison, U.S. Senator For State of Texas

Cancer is a relentless disease. It doesn’t discriminate between men and women, wealthy or poor, the elderly or the young. In 2008, over 1.4 million Americans were diagnosed with some form of the disease. If it wasn’t you, it may have been a spouse or sibling, a parent or a child, a friend or a coworker. We, too, have known the challenges of cancer diagnoses for ourselves or our family members or friends. And while there are many stories of survival, this disease still takes far too many lives. More than half a million Americans lost their battle with cancer last year.

Since the War on Cancer was declared in 1971, we have amassed a wealth of knowledge about the disease. Advances in basic and clinical research have improved treatments significantly. Some of the most important progress has been made in prevention and early detection, particularly screening, including mammography and colonoscopy. Behavior modifications, such as smoking cessation, better eating habits, regular exercise, and sunscreen have been found to prevent many cancers. Continued focus must be placed on prevention, which will always be the best cure.

Though heightened awareness and prevention should be emphasized, alone they don’t translate into adequate progress for those with cancer. Since 1971, the cancer mortality rate has decreased by only 6 percent. In the same period, by contrast, mortality rates have dramatically declined for heart disease (by 56 percent) and stroke (by 66 percent). Today, cancer is the second leading cause of death in the United States, exceeded only by heart disease. If the current trend continues, the National Cancer Institute predicts that one in every two men and one in every three women will be diagnosed with cancer in their lifetimes, and that cancer will become the leading killer of Americans.

The solution isn’t easy, but there are steps we should take now if we hope to see the diagnosis rate decline substantially and the survival rate increase.  To do so, we must identify and remove the numerous barriers that obstruct our progress in cancer research and treatment.

First, it is essential that cancer be diagnosed at an initial, curable stage. One of the most promising breakthroughs is the monitoring of biomarkers, which leave evidence within the body that alerts clinicians to hidden activity indicating that cancer may be developing. Identification of such biomarkers can lead to the earliest possible detection of cancer in patients.

Second, even if we significantly improve early detection, lack of health insurance and other impediments to care will preclude many Americans from undergoing routine screening. With early screening, the disease may be detected at a treatable stage and dramatically increase the rate of survival. Greater outreach is clearly needed to make screening more available to all, and especially to underserved populations.

Third, we must adopt a more coordinated approach to cancer research. Establishing an interconnected network of biorepositories with broadly accessible sources of tissue collection and storage will enable investigators to share information and samples much more effectively. Integrated research will help accelerate the progress of lifesaving research. The search for cures should also be a cooperative goal. The current culture of isolated career research must yield to more cooperative arrangements to expedite breakthroughs. Our national policy should encourage all stakeholders in the War on Cancer to become allies and work in concert toward cures.

Fourth, as our nation’s best and brightest researchers seek new ways to eradicate cancer, we must improve treatment for those who have it today. Raising awareness of clinical trials would result in more patients and their doctors knowing what promising trials are available. Doing so will expand treatment options for patients, and enable researchers to develop better methods for prevention, diagnosis, and therapy.  Today, less than five percent of the 10 million adults with cancer in the United States participate in clinical trials. Disincentives by the health insurance market, preventing patients from enrolling in clinical trials, must be eliminated.

Finally, as our knowledge of cancer advances and patients live longer, we need a process that will improve patient survivorship through comprehensive care planning services. There is great value in equipping patients with a treatment plan and summary of their care when they first enter remission, in order to achieve continuity of therapy and preventing costly, duplicative, or unnecessary services.

We have introduced bipartisan legislation to bring about these necessary changes, and we hope to see the bill enacted in the coming weeks and months. These policy initiatives cannot be fully implemented without broad support and sufficient resources, and we are committed to leading this effort to completion.

It’s time to reinvigorate the War on Cancer, and more effective coordination of policy and science is indispensible for rapid progress.

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.

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:

• Partridge E, Kreimer AR, Greenlee RT et. al. Results From Four Rounds of Ovarian Cancer Screening in a Randomized Trial. Obstet Gynecol. 2009 Apr;113(4):775-782. [PDF Document].

• Combo Screening Doesn’t Spot Early Ovarian Cancer – Even finding it early may not save lives, researchers say, by Steven Reinberg, HealthDay Article, U.S. News & World Report online, March 20, 2009.

Early Detection Remains Key in Updated National Comprehensive Cancer Network (NCCN) Guidelines for Ovarian Cancer

New updates to the NCCN Clinical Practice Guidelines in Oncology™ for Ovarian Cancer were presented at the NCCN 14th Annual Conference on March 14. Notable additions to the NCCN Guidelines are a section on managing allergic reactions to chemotherapy agents and new agents for recurrence therapy. Robert J. Morgan Jr., M.D., F.A.C.P. of  the City of Hope Comprehensive Cancer Center presented the updated NCCN Guidelines that continue to stress early detection of ovarian cancer and the enrollment of patients in clinical trials.

“Early Detection Remains Key in Updated NCCN Guidelines for Ovarian Cancer

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New updates to the NCCN Clinical Practice Guidelines in Oncology™ for Ovarian Cancer were presented at the NCCN 14th Annual Conference on March 14. Notable additions to the NCCN Guidelines are a section on managing allergic reactions to chemotherapy agents and new agents for recurrence therapy. Robert J. Morgan, MD, of City of Hope Comprehensive Cancer Center presented the updated NCCN Guidelines that continue to stress early detection of ovarian cancer and the enrollment of patients in clinical trials.

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March 16, 2009

Robert J. Morgan Jr., M.D., F.A.C.P., Professor of Medical Oncology, Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA & Chair of the NCCN Guidelines Panel for Ovarian Cancer

HOLLYWOOD, FL — Improvements in screening and early detection remains the key for women with ovarian cancer according to Robert J. Morgan, MD, of City of Hope Comprehensive Cancer Center and chair of the NCCN Guidelines Panel for Ovarian Cancer. Dr. Morgan discussed the future of ovarian cancer and notable changes to the recently updated NCCN Ovarian Cancer Guidelines at the NCCN Annual Conference on Saturday, March 14.

Dr. Morgan began by explaining that the major challenge in treating ovarian cancer is that by the time the majority of patients (70 percent) are diagnosed with the disease, it has already progressed to stage III or IV. ‘We have not yet found a good way to screen the general population or even the high-risk population of women for ovarian cancer,’ he said.

New to the NCCN Guidelines is a section on the management of allergic reactions in patients receiving chemotherapy for ovarian cancer. Dr. Morgan explained the need for this section as ovarian cancer tends to respond to the same treatment repeatedly. Combined with the fact that recurrence rates of ovarian cancer are high, this can result in patients often being retreated with the same chemotherapeutic agent. Given that virtually all chemotherapy drugs have the potential to cause infusion reactions, including agents commonly used in ovarian cancer, the NCCN Guidelines Panel felt it was important to provide information on allergic reactions and recommendations on desensitization regimens.

‘Most patients experiencing allergic reactions are able to be desensitized allowing for continued chemotherapeutic treatment, which is vital to the management of ovarian cancer,’ said Dr. Morgan.

Also new to the updated NCCN Guidelines is the addition of new agents for recurrence therapy, most notably pemetrexed (Alimta®, Eli Lilly and Company) as well as recommendations for therapies based on the timing of recurrence.

‘Seventy-five to 80 percent of patients with stage III or IV ovarian cancer will experience recurrence and this recurrence can occur at any time – during treatment, within 6 months of completing treatment, or more than a year after completing treatment,’ Dr. Morgan noted. ‘In the updated NCCN Guidelines, we differentiated appropriate therapy for recurrence based upon the time frame on which it occurs.’

Additionally, Dr. Morgan referred to a clinical trial suggesting that pemetrexed is active in recurrent ovarian cancer, to support the new recommendation in the updated NCCN Guidelines.

Dr. Morgan described new updates to the Principles of Primary Surgery section in the updated NCCN Guidelines that included the recommendation to consider completion surgery for patients responsive to chemotherapy with initially unresectable residual disease, as well as recommendations relating to special circumstances including minimally-invasive procedures, and fertility sparing procedures.

Dr. Morgan also discussed recent clinical studies conducted abroad that studied the effect of chemotherapy as an up-front therapy in patients with ovarian cancer, and concluded that ‘in the United States, up-front debulking surgery remains the recommendation for the best overall survival.’

Another addition to the updated NCCN Guidelines is a section on the Principles of Chemotherapy. This section emphasizes the encouragement of patients participating in clinical trials during all aspects of their treatment course as well as noting that patients with newly diagnosed tumors should be informed about the different options available, particularly IV [intravenous] vs. IV/IP chemotherapy and the risks and benefits of each regimen.

‘The future of ovarian cancer lies in early detection and improvements in screening,’ Dr. Morgan noted as he discussed potential biomarkers for the detection, prediction and prognostication of ovarian cancer.

He concluded that steady progress is being made in the treatment of ovarian cancer, but further trials are necessary to investigate the role of targeted agents alone and in combination in newly diagnosed and recurrent ovarian cancer. Finally, he again stressed the need for physicians to encourage their patients to participate in clinical trials.

For questions about NCCN or for interview information, please contact Megan Martin 215.690.0576.

About the National Comprehensive Cancer Network

The National Comprehensive Cancer Network (NCCN), a not-for-profit alliance of 21 of the world’s leading cancer centers, is dedicated to improving the quality and effectiveness of care provided to patients with cancer. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers. The primary goal of all NCCN initiatives is to improve the quality, effectiveness, and efficiency of oncology practice so patients can live better lives. For more information, visit www.nccn.org.

The NCCN Member Institutions are

• City of Hope Comprehensive Cancer Center
• Dana-Farber/Brigham and Women’s Cancer Center
• Massachusetts General Hospital Cancer Center
• Duke Comprehensive Cancer Center
• Fox Chase Cancer Center
• Huntsman Cancer Institute at the University of Utah
• Fred Hutchinson Cancer Research Center / Seattle Cancer Care Alliance
• Arthur G. James Cancer Hospital & Richard J. Solove Research Institute at The Ohio State University
• The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Robert H. Lurie Comprehensive Cancer Center of Northwestern University
• Memorial Sloan-Kettering Cancer Center
• H. Lee Moffitt Cancer Center & Research Institute
• Roswell Park Cancer Institute
• Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
• St. Jude Children’s Research Hospital / University of Tennessee Cancer Institute
• Stanford Comprehensive Cancer Center
• University of Alabama at Birmingham Comprehensive Cancer Center
• UCSF Helen Diller Family Comprehensive Cancer Center
• University of Michigan Comprehensive Cancer Center
• UNMC Eppley Cancer Center at The Nebraska Medical Center
• The University of Texas M. D. Anderson Cancer Center
• Vanderbilt-Ingram Cancer Center”

Cited Source:  Early Detection Remains Key in Updated NCCN Guidelines for Ovarian Cancer, News, National Comprehensive Cancer Network (NCCN), March 16, 2009.

Lost In Translation? FDA Believes That LabCorp’s Ovarian Cancer Early Detection Test (OvaSure) Lacks Adequate Clinical Validation

The U.S. Food and Drug Administration (FDA) sent a letter to the Laboratory Corporation of America (LabCorp) on August 7, 2008, stating that it believes the Yale ovarian cancer early detection test (marketed by LabCorp under the name OvaSure™) ” … has not received adequate clinical validation, and may harm the public health.” In that letter, the FDA invites LabCorp to discuss all validation studies that support the marketing of the OvaSure™ test.

The U.S. Food and Drug Administration (FDA) sent a letter to the Laboratory Corporation of America (LabCorp) on August 7, 2008, stating that it believes the Yale ovarian cancer early detection test (marketed by LabCorp under the name OvaSure™) “… has not received adequate clinical validation, and may harm the public health.” In the letter, the FDA invites LabCorp to discuss all validation studies that support the marketing of the OvaSure™ test. The August 7 FDA letter appears to reflect a previously announced, yet controversial, change in FDA policy. Libby’s H*O*P*E*™ reported previously on the development of the Yale ovarian cancer early detection test [March 14, 2008], and LabCorp’s subsequent market release of that test under the name OvaSure™ [June 23, 2008].

On August 19, 2008, the Oncology STAT™ news service reported that the August 7 FDA letter was posted on the website of the Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD) on August 15, but was removed from the site a few days later. On August 22, 2008, we identified the “cached” copy of the August 7 FDA letter on the OIVD website. The August 7 FDA letter is provided below in its entirety.

The August 7 FDA letter was issued by OIVD and informs LabCorp that “[i]t appears that you are marketing the Ovasure™ Test with performance characteristics (specifically, 95.3% sensitivity and 99.4% specificity) that are identical to those reported in a research study published by Visintin, I. et al., in the February 15 edition of Clinical Cancer Research (Visintin, I. et al., Clin Cancer Res. 2008 Feb 15;14(4):1065-72.).” The OIVD Director, Steven Gutman, M.D., M.B.A., states that the Visintin, I. et. al ” … research was carried out, and performance derived, on two populations that are strongly clinically biased for being healthy and normal, and for having already experienced ovarian cancer.” Based upon this rationale, the OIVD concludes that it does not believe “… the scientific community would consider the reported study sufficient to establish performance characteristics of a test in high risk women who might have ovarian cancer, i.e., in a clinical setting, as claimed in your intended use and promotional materials.”

Historical FDA Policy Regarding Laboratory-Developed (“Home Brew”) Tests

Based upon historical FDA policy, LapCorp would not be required to obtain FDA premarket or postmarket approval for the OvaSure™ test because the early detection test would be categorized as a “laboratory-developed test” (also referred to as a “home brew” test) under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). In general, the CLIA establishes quality standards for all laboratory testing to ensure the accuracy, reliability and timeliness of patient test results regardless of where the test is performed.

Prior to 2006, the FDA did not exercise its authority to regulate home brew tests, which are developed by a laboratory for in-house use as a test service. The reasons are likely twofold. First, the FDA believed that the regulatory oversight exercised by the Centers for Medicare & Medicaid Services (CMS) with respect to the laboratories (under CMS jurisdiction pursuant to CLIA), ensured that such laboratories were competent to properly manufacture and use home brew tests without additional FDA intervention. Second, the FDA possessed regulatory authority to review the primary ingredients or components in the home-brew tests (known as “analyte specific reagents” (ASRs)), and did not believe that further test regulation was necessary.

Announcement of FDA Policy Change For Select In Vitro Diagnostic Assays

In 2006, and again in 2007, the FDA issued draft guidance (entitled, Draft Guidance for Industry, Clinical Laboratories, and FDA Staff: In Vitro Diagnostic Multivariate Index Assays) in which, for the first time, the agency exercised its authority to regulate select in vitro diagnostic multivariate index assays (“IVDMIAs”) that are developed and manufactured by clinical laboratories for their own use (i.e., laboratory-developed tests/home brew tests). An IVDMIA is a diagnostic laboratory assay or test that utilizes mathematical formulae to interpret genetic and protein data required for the generation of information used to make critical diagnosis and treatment decisions for patients. IVDMIAs, for FDA regulatory purposes, are classified as medical devices under the Federal Food, Drug & Cosmetic Act (FDCA), and therefore, can be subject to premarket and postmarket regulation. IVDMIAs developed and manufactured by commercial, non-laboratory-based companies are currently regulated by the FDA. The majority of IVDMIAs, however, are developed and manufactured by laboratories for their own use as home brew tests.

Under the FDA draft guidance, home brew IVDMIAs would in many cases require 510(k) pre-market clearance or Pre-Market Approval (PMA). In addition, these same IVDMIAs would have to comply with “device” post-market manufacturing and reporting requirements. The August 7 FDA letter does not state that a 510(k) pre-market clearance or Pre-Market Approval is required; rather OIVD invites LabCorp to discuss any “validation strategies” undertaken beyond the research results reported by Visintin, I. et. al. LabCorp is not the only company affected by the FDA policy change. The FDA also used its change in regulatory policy to prevent Correlogic Systems, Inc. from marketing its ovarian cancer early detection test, known as OvaCheck®, without prior FDA approval. Arguably, the FDA is placing the OvaSure™ and OvaCheck® ovarian cancer early detection tests on equal regulatory footing.

Ever-Increasing Sophistication of Genetic and Proteomic Assay Technology

The emergence and increased use of IVDMIAs using novel technology (e.g., proteomics) as an integral part of patient diagnosis and treatment, and their direct advertisement to consumers, may have influenced the FDA to conclude more recently that the current level of oversight with respect to genetic and proteomic testing by laboratories was inadequate. Assuming the FDA position is correct, inadequate federal oversight could lead to significant issues related to the quality and validity of IVDMIAs.

LabCorp Amendment of OvaSure™ “Use” Information

LabCorp recently amended its intended use and promotional materials to provide that the OvaSure™ test cannot be used by a woman who has had both ovaries removed (i.e., a woman who previously had a bilateral oophorectomy). Specifically, LabCorp intends that the OvaSure™ test be used to identify a woman who is at “high-risk” for ovarian cancer; however, an ovarian cancer survivor who is currently in remission, cannot use the OvaSure™ test to screen for a recurrence of the disease if her ovaries were removed as part of her first-line treatment after the initial ovarian cancer diagnosis. CLICK HERE to view Libby’s H*O*P*E* post (with updates) dated June 23, 2008, regarding the OvaSure™ test use and limitation information as amended.

Letter to the President and Chief Executive Officer of LabCorp

August 7, 2008
Via FedEx

David P. King
President and Chief Executive Officer
Laboratory Corporation of America
430 South Spring Street
Burlington, North Carolina 27215

Dear Mr. King:

It has come to our attention that you are currently marketing the OvaSure™ Yale Ovarian Cancer Test, also advertised as the OvaSure™ For Women at High-Risk for Ovarian Cancer, and OvaSure™ For Women at High-Risk for Ovarian Cancer, (Serial Monitor), (collectively referred to hereafter as the OvaSure™ Test) which is intended to be used as a tool to identify high-risk women who might have ovarian carcinoma. It appears that you are marketing the OvaSure™ Test with performance characteristics (specifically, 95.3% sensitivity and 99.4% specificity) that are identical to those reported in a research study published by Visintin, I., et al., in the February 15 edition of Clinical Cancer Research (Visintin, I. et al., Clin Cancer Res. 2008 Feb 15;14(4):1065-72.). We note that this research was carried out, and performance derived, on two populations that are strongly clinically biased for being healthy and normal, and for having already experienced ovarian cancer. Based on the available information, we do not believe the scientific community would consider the reported study sufficient to establish performance characteristics of a test in high risk women who might have ovarian cancer, i.e., in a clinical setting, as claimed in your intended use and promotional materials.

Based on our review of your promotional materials and the research publication cited above, we believe you are offering a high risk test that has not received adequate clinical validation, and may harm the public health. We would like to discuss with you your offer of this test, and any validation strategies you have undertaken beyond those reported in the publication cited above.

We look forward to discussing this with you, and are committed to working with you as we strive to protect the public health without unnecessarily imposing regulatory burdens on the marketing of products of potential clinical importance.

Sincerely yours,

/S/

Steven I. Gutman, M.D., M.B.A.
Office Director
Office of In Vitro Diagnostic Device Evaluation and Safety
Center for Devices and Radiological Health

Comments:

• The corporate and governmental intrigue surrounding the FDA regulatory issues with respect to the OvaSure™ and OvaCheck® ovarian cancer early detection tests would make for a thrilling Hollywood screenplay, except for the catastrophic fact that approximately 15,000 U.S. women die annually from ovarian cancer due to the lack of a reliable early detection test. Because of the latter, approximately 80 percent of women are not diagnosed until they are in advance stages of the disease.

• The FDA’s current – and still evolving – policy signals a strong possibility that previously unregulated diagnostics could require FDA approval or clearance prior to marketing as well as being subject to other medical device requirements under the FDCA.

• It is critical for the FDA to take whatever action is necessary to protect U.S. public health. It is also essential that ovarian cancer survivors, clinicians and all affected corporate entities receive clear, consistent regulatory guidance and prompt action from the FDA with respect to this potential life-saving matter.

Sources:

• FDA Questions LabCorp in Its Ovarian Cancer Test Service, OncologySTAT™ News, Week in Review, Issue 33, Aug. 22, 2008 (reprinting article by D. Filmore, The Pink Sheet Daily, Aug. 19, 2008).
• Draft Guidance for Industry,Clinical Laboratories, and FDA Staff: In Vitro Diagnostic Multivariate Index Assays, July 26, 2007 (Adobe Reader PDF doc.)
• Office of In Vitro Diagnostic Device Evaluation & Safety, Centers For Devices and Radiological Health, U.S. Food & Drug Administration (online).
• Clinical Laboratory Improvement Amendments (CLIA) (online), Centers for Medicare & Medicaid Services, U.S. Department of Health & Human Services.
• CLIA-Clinical Laboratory Improvement Amendments (online), Center For Devices and Radiological Health, U.S. Food & Drug Administration
• Clinical Proteomics Advances as Vermillion, LabCorp, Correlogic Prep For Market, by Bernadette Toner, ProteoMonitor, June 26, 2008 (online version)
• Recent U.S. Regulatory Developments Herald Increasing FDA Regulation of Laboratory-Developed Diagnostic Tests and Services, by Jane E. Baluss, The Pulse publication, Foley & Lardner LLP, October 5, 2007.
• Significant extension of FDA regulatory oversight over certain “home brew” laboratory tests, by Jill Alvarez & Teresa Kelto, FDA Alert (a publication of Nixon Peabody LLP), Sept. 25, 2006.

Updates:

• August 25, 2008: Cancer Test For Women Raises Hope, and Concern, by Andrew Pollack, Health Section (online edition), The New York Times, Aug. 25, 2008 (Aug. 26, p. F1. NY print edition).

• September 9, 2008: The FDA recently reposted on its website, a copy of the August 7th letter to the President and Chief Executive Officer of LabCorp regarding OvaSure™. To view a copy of the letter, CLICK HERE.

• October 8, 2008: FDA Issues A Warning Letter to LabCorp Regarding The Illegal Marketing of the OvaSure™ Test, by Paul Cacciatore, Libby’s H*O*P*E*, Oct. 8, 2008.

Symptom Screening + CA-125 Blood Test = Better Detection of Early Stage Ovarian Cancer

” …Research has found that when used alone, a simple four-question symptom-screening questionnaire and the CA125 ovarian-cancer blood test each detect about 60 percent of women with early-stage ovarian cancer and 80 percent of those with late-stage disease. This study found that when used together, the questionnaire and blood test may boost early-detection rates to more than 80 percent and late-stage detection rates to more than 95 percent. …”

“Women’s reports of persistent, recent-onset symptoms linked to ovarian cancer – abdominal or pelvic pain, difficulty eating or feeling full quickly and abdominal bloating – when combined with the CA125 blood test may improve the early detection of ovarian cancer by 20 percent, according to new findings by researchers at Fred Hutchinson Cancer Research Center published online today in CANCER.

Research has found that when used alone, a simple four-question symptom-screening questionnaire and the CA125 ovarian-cancer blood test each detect about 60 percent of women with early-stage ovarian cancer and 80 percent of those with late-stage disease. This study found that when used together, the questionnaire and blood test may boost early-detection rates to more than 80 percent and late-stage detection rates to more than 95 percent.

‘Of course, it is the increase in the detection of early-stage disease that is the most exciting,’ said lead author M. Robyn Andersen, Ph.D., an associate member of the Public Health Sciences Division at the Hutchinson Center. Cure rates for those diagnosed when the disease is confined to the ovary are approximately 70 percent to 90 percent. However, more than 70 percent of women with ovarian cancer are diagnosed with advanced-stage disease, when the survival rate is only 20 percent to 30 percent.

‘This research suggests that if a woman has one or more symptoms that are new for her, having begun within the past year, and if the symptoms happen nearly daily or at least 12 times a month, that may well be a signal to go in and discuss those symptoms with her doctor,’ Andersen said. ‘It’s probably not going to be ovarian cancer, just as most breast lumps are not breast cancer, but it’s still a sign that it might be worth checking with her doctor to see if a CA125 blood test and transvaginal ultrasound may be appropriate.’

Assessing the symptoms included in the symptom-screening index may already be done by some doctors based on a consensus statement issued last year by the National Institutes of Health. The researchers hope their symptom index will help doctors know which among their patients who complain of symptoms such as abdominal swelling and pelvic pain might have cancer.

The symptom-screening index, developed in 2006 by paper co-author Barbara A. Goff, M.D., professor and director of Gynecologic Oncology at the University of Washington School of Medicine, is not used proactively in clinical general practice, but Andersen and colleagues are conducting a pilot study to assess the value of using it as a screening tool among normal-risk women as part of their routine medical-history assessment.

For the just-published study, the researchers administered the symptom questionnaire to 75 women about to undergo surgery for pelvic masses who were later diagnosed with ovarian cancer (the case group), and 254 healthy women at high risk for ovarian cancer due to a family history of the disease (the control, or comparison, group). The cases were recruited through Pacific Gynecology Specialists at Swedish Medical Center in Seattle, and the controls were recruited through the Ovarian Cancer Early Detection Study, a joint project of the Hutchinson Center and the Marsha Rivkin Center for Ovarian Cancer Research.

The National Institutes of Health/National Cancer Institute, the Marsha Rivkin Center for Ovarian Cancer Research and the Canary Foundation supported this research.”

[Quoted Source: Symptom screening plus a simple blood test equals a 20 percent jump in early detection of ovarian cancer, Fred Hutchinson Cancer Research Center News Release, June 23, 2008.]

LabCorp Announces Availability of Ovarian Cancer Blood Test To Assess The Presence of Early Stage Ovarian Cancer

“Laboratory Corporation of America® Holdings is now offering OvaSure™, an Ovarian Cancer Screening test to assess the presence of early stage ovarian cancer in high-risk women. In a recent study of high risk and average risk subjects, this blood test, using six biomarkers and research conducted at Yale University School of Medicine, was shown to discriminate between disease-free women and ovarian cancer patients (stage I-IV) with high specificity (99.4%) and sensitivity (95.3%). Additional studies performed at Yale University School of Medicine demonstrate comparable findings.”

On March 14, 2008, the H*O*P*E*™ weblog reported that a new blood test developed by the Yale University School of Medicine detected early stage ovarian cancer with 99% accuracy in Phase II clinical trial testing. To review the March 14 H*O*P*E*™ weblog post, click here. In 2006, Laboratory Corporation of America (Lab Corp) obtained licensing rights to the ovarian cancer early detection blood test, known as OvaSure™, from Yale. Today, Lab. Corp. announced in a press release that it is making the OvaSure™ blood test immediately available nationwide to women who are at high risk of developing ovarian cancer in the future. The relevant portion of the Lab Corp. press release dated June 23, 2007 is set forth below.

“LabCorp Announces Availability of OvaSure™

Burlington, NC, June 23, 2008 – Laboratory Corporation of America® Holdings (LabCorp®) (NYSE: LH) is now offering OvaSure™, an Ovarian Cancer Screening test to assess the presence of early stage ovarian cancer in high-risk women. In a recent study of high risk and average risk subjects, this blood test, using six biomarkers and research conducted at Yale University School of Medicine, was shown to discriminate between disease-free women and ovarian cancer patients (stage I-IV) with high specificity (99.4%) and sensitivity (95.3%). Additional studies performed at Yale University School of Medicine demonstrate comparable findings.

‘LabCorp is pleased to offer for high-risk women the OvaSure test to enhance the potential of detecting and treating ovarian cancer in its early or localized stage when the likelihood of survival is greatest,’ said Myla P. Lai-Goldman, M.D., Executive Vice President, Chief Medical Officer of LabCorp. ‘OvaSure is a significant addition to LabCorp’s family of proteomic tests, and a major component of LabCorp’s strategy to bring the latest in diagnostic technology to women’s healthcare.’

It has been estimated that for the year 2008, 21,650 women will be newly diagnosed with ovarian cancer. It has been further estimated that 15,520 women will die from the disease in 2008. Despite being one-eighth as common as breast cancer, it is three times more lethal. If ovarian cancer is diagnosed and treated at the localized stage, the 5-year survival rate is 92%; unfortunately, only 19% of all cases are found at the localized stage. Most women have their ovarian cancer detected at the regional or distant stage when the 5-year survival rates are 71% and 30% respectively.

‘I am pleased that this test is available to help physicians detect and treat ovarian cancer in its earliest stages,’ said Gil Mor, M.D., associate professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale and a member of Yale Cancer Center. ‘Our team is proud that our research may help play a role in higher survival rates for women with this disease.’”

[Quoted Source: LabCorp Announces Availability of OvaSure™ , Laboratory Corporation of America Press Release dated June 23, 2008.]

Comment**: Although additional Phase III clinical trial testing with a larger patient population is required, the OvaSure™ blood test may represent the “gold standard” for early stage ovarian cancer detection in the near future. The immediate availability of the OvaSure™ blood test for use by women who are at high risk for developing ovarian cancer could save lives by catching ovarian cancer in its earliest stages, thereby making treatment of the disease highly effective. To view the ABCNews.com news report regarding the Yale ovarian cancer screening blood test that aired on April 21, 2008, click here.

**As of August 21, 2008, the amended OvaSure™ test “use” information provides, among other things, that a woman who has had both ovaries removed (i.e., a bilateral oophorectomy) should not use the test. Accordingly, it appears that the OvaSure™ test cannot be used by a “high-risk” woman to screen for an ovarian cancer recurrence, if she had both ovaries removed as part of her first line treatment following initial diagnosis of the disease.

OvaSure™ Information: The OvaSure™ blood test is now available nationwide through LabCorp. If you want to review OvaSure™ blood test information on the LabCorp. website, click here (then click on the letter “O” located on the upper left side panel keyboard and scroll down until you find the three OvaSure™ blood test information entries). It is our understanding that the OvaSure™ test cost approximately (U.S.)$225 and test results are available within five business days.

OvaSure™ Use (updated 8/21/08): “The OvaSure^TM assay may be used as a tool to identify high-risk women who might have ovarian carcinoma. OvaSure^TM is not indicated for a patient who is currently undergoing chemotherapy, who has had both ovaries removed, who is pregnant, or who is lactating. About 10% of women with benign ovarian masses (including cysts) may have positive results by this test.”

OvaSure™ Limitations (updated 8/21/08) : “Pregnant women or women who are lactating should not be screened by the assay because it may lead to false-positive results. A Calculated Risk Index of 0.50 or greater indicates a positive reading, which is suggestive of ovarian cancer (possible presence of disease). In a clinical study (see Journal Abstract below) across all disease stages, the six-marker panel composed of leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factor, and CA-125 demonstrated a sensitivity of 95.3% and a specificity of 99.4% in detecting disease. Greater than 99% sensitivity (119 of 120) was shown in late-stage disease (stage III and stage IV). In early stage disease (stage I and stage II), the assay demonstrated a sensitivity of 91.6%, providing a significant improvement over CA-125 alone (less than 60% of stage I and stage II combined) for ovarian cancer detection. All positive readings should be retested on a new sample drawn at least three weeks after the original sample was collected. Patients with positive results confirmed by retesting on a second sample should be followed by a women’s health specialist who may order additional evaluations, such as sensitive imaging. Components used in this test are labeled as research purposes only. The performance characteristics of this product have not been established by the assay manufacturer. Results should not be used as a diagnosis for ovarian cancer without confirmation of the diagnosis by another medically established diagnostic product or procedure.”

OvaSure™ Journal Abstracts and Full Text Studies:

• Diagnostic markers for early detection of ovarian cancer; Visintin, I. et. al., Clin Cancer Res. 2008 Feb 15;14(4):1065-72. Epub 2008 Feb 7. Click here for an Adobe Reader PDF copy of the complete study text.
• Serum protein markers for early detection of ovarian cancer, Mor G et. al., Proc Natl Acad Sci U S A. 2005 May 24;102(21):7677-82. Epub 2005 May 12. Click here for an Adobe Reader PDF copy of the complete study text.

Updates:

• July 2, 2008: The Society of Gynecologic Oncologists (SGO) issued a statement regarding the Labcorp OvaSure™ test. The SGO statement, dated July 2, 2008, is quoted below in its entirety.

“July 2, 2008

Society of Gynecologic Oncologists
Statement Regarding OvaSure^TM

The Society of Gynecologic Oncologists (SGO) recognizes the need for accurate early detection biomarkers for ovarian cancer. For this reason, SGO reviewed the literature regarding OvaSure, a serum-based diagnostic test for ovarian cancer.

After reviewing OvaSure’s materials, it is our opinion that additional research is needed to validate the test’s effectiveness before offering it to women outside of the context of a research study conducted with appropriate informed consent under the auspices of an institutional review board.

SGO is committed to actively following and contributing to this vitally important research. As physicians who care only for women with gynecologic cancers, our hope is that these cancers can either be prevented or detected early. Because no currently available test has been shown to reliably detect ovarian cancer in its earliest and most curable stages, we will await the results of further clinical validation of OvaSure with great interest.”

The SGO is a national medical specialty organization of physician-surgeons who are trained in the comprehensive management of women with malignancies of the reproductive tract. The purpose of the SGO is to improve the care of women with gynecologic cancers by encouraging research and disseminating knowledge to raise the standards of practice in the prevention and treatment of gynecologic malignancies, in cooperation with other organizations interested in women’s health care, oncology and related fields.

Quoted Update Source: Society of Gynecologic Oncologists Statement Regarding OvaSure™, Society of Gynecologic Oncologists, July 2, 2008 (Adobe Reader PDF document).

Other Update Sources: Fast Facts: Background on The Society of Gynecologic Oncologists, Society of Gynecologic Oncologists Press Kit, undated.

• August 12, 2008: The ROC ‘n’ role of the multiplex assay for early detection of ovarian cancer, Nick AM, Sood AK; Nat Clin Pract Oncol. 2008 Aug 12. [Epub ahead of print] (medical abstract text quoted below) —

“AM Nick is a Fellow in the Department of Gynecologic Oncology, and AK Sood is the Bettyann Asche-Murray Distinguished Professor in the Department of Gynecologic Oncology and in the Department of Cancer Biology, both at the University of Texas MD Anderson Cancer Center, Houston, TX, USA.

In order to overcome the significant mortality associated with ovarian cancer, a highly sensitive and specific screening test is urgently needed. CA125 is used to assess response to chemotherapy, detect recurrence, and distinguish malignant from benign disease; however, this marker is elevated in only 50-60% of stage I ovarian cancers, making it inadequate for early detection of malignancy. In this Practice Point, we discuss Visintin et al.‘s attempt to validate a novel multiplex assay that uses a panel of six serum biomarkers-leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factor, and CA125 [medical abstract & full text of Visintin et. al. study provided above]. The study included 362 healthy controls and 156 patients with newly diagnosed ovarian cancer. The final model yielded 95.3% sensitivity, 99.4% specificity, a positive predictive value of 99.3% and a negative predictive value of 99.2%. These results indicate potential utility of this assay for early detection of ovarian cancer, although further validation is needed in a sample set representative of the general population.”

• August 21, 2008: The Labcorp information with respect to the OvaSure™ test was recently modified. Despite that fact that the test was made available for “high-risk” women, it cannot be used by women who have had both ovaries removed. Consequently, it appears that a woman who had both ovaries removed (i.e., bilateral oophorectomy) after an initial diagnosis of ovarian cancer, cannot use the OvaSure™ test to screen for a potential recurrence of the disease in the future.

• August 23, 2008:  Lost In Translation? FDA Believes That LabCorp’s Ovarian Cancer Early Detection Test (OvaSure) Lacks Adequate Clinical Validation, Libby’s H*O*P*E*, August 23, 2008.