An Attitude of Gratitude On Thanksgiving Day

“Gratitude unlocks the fullness of life. It turns what we have into enough, and more. It turns denial into acceptance, chaos to order, confusion to clarity. It can turn a meal into a feast, a house into a home, a stranger into a friend. Gratitude makes sense of our past, brings peace for today, and creates a vision for tomorrow.” — Melody Beattie

Today, many of us will celebrate a national day of Thanksgiving with family and friends. You know the drill — eating turkey, mash potatoes, stuffing, and pumpkin or apple pie; watching football (your pick of Green Bay Packers vs. Detroit Lions, Miami Dolphins vs. Dallas Cowboys, or San Francisco 49ers vs. Baltimore Ravens); and napping, after which the whole cycle begins anew.

Why Be Grateful?

Within this traditional celebration, it is all too easy for us to lose sight of the real meaning of the holiday; that is, to give thanks for the many blessings bestowed upon us in our daily lives. Yesterday, I overheard two adults speaking about Thanksgiving in a grocery store line. One individual said to the second in a serious tone: “What do I have to be thankful for?” At first blush, it seems like a fair question when you consider the following:

• The U.S. is currently engaged in two major armed conflicts. As of November 22, the total number of Americans killed in Afghanistan and Iraq is 4,984, and the number of wounded is over 47,000. The conflict in Afghanistan hit the 10-year mark in October. In contrast, the U.S. forced the unconditional surrender of Nazi Germany and the Imperial Empire of Japan in 3 years and 8 months, thereby ending World War II in August 1945.

• The U.S. is experiencing the worst economic downturn since “The Great Depression” of the 20th century.

• The bipartisan U.S. Congressional “Super Committee” failed to reach agreement on $1.2 trillion of federal budget spending cuts over the next ten years, as part of Congress’ ongoing theater of the absurd in which its utter and total failure is “spun” as success.

• The U.S. Congress’ approval rating, based upon a recent New York Times poll, sits at an all-time low of 9 percent. By comparison, former President Richard Nixon’s final approval rating after the Watergate Scandal and upon his resignation was 23%.

• The U.S. National Cancer Institute (NCI) continues to fight for increased federal funding for cancer research in a time when 50% of men and 33% of women woman will experience cancer at some point during their lifetimes.

• It is estimated that 15,460 U.S. women will die from ovarian cancer in 2011, which represents the death of one woman every 37 minutes. The annual U.S. ovarian cancer death toll is equal to the number of passenger deaths that would result from 30 Boeing 747 airplane crashes every year.

• According to a recently published U.K. report, the median survival of women with ovarian cancer only increased from 8 months to 3 years over the past 40 years.

There is little doubt that the current state of U.S. affairs as described above is indeed daunting. The unsettling situation in the U.S., however, pales in comparison to the average life experience of those living in extreme poverty around the world (including the U.S.).

• In 2005, the World Bank reported that 1.4 billion people in the developing world (one in four) were living on less than US$1.25 per day, of which 162 million live on less than $0.50 per day. The latter category of individuals are referred to as the “ultra poor” by the International Food Policy Research Institute.

• Number of children in the world: 2.2 billion. Number of children living in poverty: 1 billion.

• According to the World Health Organization, there are approximately 33 million people living with HIV/AIDS today, with 2 million AIDS-related deaths anticipated each year. It is estimated that 76% of those deaths will occur in sub-Saharan Africa.

• The United Nations estimates that 34,000 children and 16,000 adults die each day from hunger or preventable diseases with poverty-related causes. The annual death total is 18 million per year, which is nearly two times greater than the total number of deaths that occurred throughout “The Holocaust” between 1933 and 1945.

• Approximately 1.1 billion people in developing countries have inadequate access to clean water, and 2.6 billion lack basic sanitation. Approximately 12 percent of the world’s population uses 85 percent of its water, and the individuals represented by the 12 percent do not live in the Third World.

• In 1997, it was estimated that less than 1 percent of annual world weapons expenditures was needed to put every child into school by the year 2000.

• Nearly one billion people entered the 21st century unable to read a book or sign their names.

• 1.6 billion people live without electricity.

• The U.S. has the widest gap between rich and poor of any industrialized nation.

• In 2008, 7.6 million people died of cancer or 13% of all deaths worldwide. About 70% of all cancer deaths occur in low- and middle-income countries.

In light of the above-mentioned global poverty statistics, it should be possible for even the most pessimistic U.S. citizen to be grateful on Thanksgiving Day. For the women and families who are dealing with ovarian cancer in their lives, we also believe that gratitude and hope is not only possible; it is essential.

• While cancers (including ovarian) constitute an incredibly diverse and bewilderingly complex set of diseases, we have at hand the methods to identify essentially all of the genetic changes in a cell and to use that knowledge to rework the landscape of cancer research and cancer care, from basic science to prevention, diagnosis, and treatment.

• With this better understanding of cancer and recent technological advances in many fields, such as genomics, molecular biology, biochemistry, and computational sciences, progress has been made on many fronts, and a portrait is beginning to emerge for several cancers including ovarian.

• It has been established that there are at least four major subtypes of epithelial ovarian cancer which should be treated as separate and distinct diseases.

• In The Cancer Genome Atlas (TCGA) study findings recently published with respect to the most common form of epithelial ovarian cancer, the investigators reported that a class of drugs known as “PARP inhibitors” may benefit up to 50% of high-grade, serous ovarian cancer (HGS-OvCa) survivors. In that same study, the investigators identified 22 genomic targets that occur in 10% or more of these cases, along with nearly 100 preclinical, clinical and FDA-approved drugs which are capable of “hitting” those targets.

• The TCGA study of HGS-OvCa is arguably the world’s largest genomic study of any form of cancer to date.

• Never before in human history has so much healthcare information been so readily available to the general public, thereby allowing cancer survivors and their families to proactively participate with their doctors in decisions relating to cancer diagnoses, treatments, and survivorship.

• Given the rapid technological and pharmacological developments described above, it is important to “live to fight another day.”

• Studies suggest that gratitude may improve overall health by leading to (i) better diet, (ii) increased amounts of exercise, (iii) reduced stress, and (iv) a stronger immune system. In other words, if you want to promote health, try giving thanks.

Thanksgiving In Times of Adversity & Plenty

“… As we gather in our communities and in our homes, around the table or near the hearth, we give thanks to each other and to God for the many kindnesses and comforts that grace our lives. Let us pause to recount the simple gifts that sustain us, and resolve to pay them forward in the year to come. …” — President Barack Obama

On November 16, 2011, U.S. President Barack Obama issued a Presidential Proclamation for Thanksgiving Day 2011. The proclamation is befitting of the true meaning underlying this traditional holiday. Although the origins of the modern U.S. Thanksgiving holiday can be traced back to the early 17th century, it is worth noting that the first Thanksgiving to be celebrated by all U.S. states on the same day (i.e., the final Thursday of November, which was not enacted into law by Congress until December 1941) was first proclaimed by President Abraham Lincoln on October 3, 1863. The year 1863 was arguably one of the darkest time periods in U.S. history because it occurred in the midst of the Civil War; a conflict that pitted brother against brother, and resulted in more American deaths than all subsequent U.S. conflicts combined. Despite that fact, President Lincoln believed strongly that we should give thanks for our daily blessings even in times of great adversity.

The main text of President Obama’s proclamation, which is provided below, echoes the sentiments of Lincoln and reminds all Americans that in good times and bad times, “… we have lifted our hearts by giving humble thanks for the blessings we have received and for those who bring meaning to our lives.”

“One of our Nation’s oldest and most cherished traditions, Thanksgiving Day brings us closer to our loved ones and invites us to reflect on the blessings that enrich our lives. The observance recalls the celebration of an autumn harvest centuries ago, when the Wampanoag tribe joined the Pilgrims at Plymouth Colony to share in the fruits of a bountiful season. The feast honored the Wampanoag for generously extending their knowledge of local game and agriculture to the Pilgrims, and today we renew our gratitude to all American Indians and Alaska Natives. We take this time to remember the ways that the First Americans have enriched our Nation’s heritage, from their generosity centuries ago to the everyday contributions they make to all facets of American life. As we come together with friends, family, and neighbors to celebrate, let us set aside our daily concerns and give thanks for the providence bestowed upon us.

Though our traditions have evolved, the spirit of grace and humility at the heart of Thanksgiving has persisted through every chapter of our story. When President George Washington proclaimed our country’s first Thanksgiving, he praised a generous and knowing God for shepherding our young Republic through its uncertain beginnings. Decades later, President Abraham Lincoln looked to the divine to protect those who had known the worst of civil war, and to restore the Nation “to the full enjoyment of peace, harmony, tranquility, and union.”

In times of adversity and times of plenty, we have lifted our hearts by giving humble thanks for the blessings we have received and for those who bring meaning to our lives. Today, let us offer gratitude to our men and women in uniform for their many sacrifices, and keep in our thoughts the families who save an empty seat at the table for a loved one stationed in harm’s way. And as members of our American family make do with less, let us rededicate ourselves to our friends and fellow citizens in need of a helping hand.

As we gather in our communities and in our homes, around the table or near the hearth, we give thanks to each other and to God for the many kindnesses and comforts that grace our lives. Let us pause to recount the simple gifts that sustain us, and resolve to pay them forward in the year to come. …” — Barack Obama’s Presidential Proclamation — Thanksgiving Day, 2011

If All Else Fails  — Try Humor

If you are still having trouble cultivating an attitude of gratitude on Thanksgiving Day, it is always helpful to enjoy the humor created by a child’s perspective. Thanksgiving is a time for food, family and fun, and we all know that children and grandchildren are a big part of the fun. Save Mart Supermarkets dared to create a video which captures a child’s perspective on the traditional Thanksgiving experience.  We should warn you that a broad smile is a common side effect of watching this video. Enjoy!

What Are We Thankful For?

Our Thanksgiving Day gratitude list includes the following:

• Ovarian cancer survivors and their families, who teach us every day about the importance of hope, perseverance, courage, compassion, love, and acceptance.

• The compassion of medical clinicians who treat ovarian cancer patients every day.

• The intelligence and dedication of U.S. and international medical and scientific researchers, who doggedly pursue methods to control, and ultimately conquer, ovarian cancer.

• The generous assistance provided to us by the Women’s Oncology Research & Dialogue (WORD) gynecological cancer awareness organization. Dr. Kelly Manahan (WORD Co-Founder), Dr. John Geisler (WORD Co-Founder), Nate Manahan (WORD Executive Director) and Chad Braham (WORD Director of Media Productions) provide Libby’s H*O*P*E* with invaluable substantive and technical assistance throughout the year, including the newest joint collaboration called “WORD of HOPE Ovarian Cancer Podcast.”

• The substantive assistance provided to us by the Ovarian Cancer Research Program of British Columbia, the British Columbia Cancer Agency, and the BC Cancer Foundation.

• The ongoing generosity, encouragement and hope provided by Douglas and Diana Gray through the Gray Family Ovarian Clear Cell Carcinoma Research Resource, a multi-year research project dedicated to understanding, and ultimately defeating, one of the most lethal subtypes of epithelial ovarian cancer.  The Talmud says: “And whoever saves a life, it is considered as if he saved an entire world.” Doug and Diana Gray are passionate about pioneering ovarian cancer research aimed at saving women’s lives.

• Our families who provide seemingly endless support and understanding, while we advocate on behalf of ovarian cancer survivors and their families.

• The inspiration provided by Libby’s eternal spirit.

• The ovarian cancer advocacy communities represented on Facebook, Twitter, Inspire.com, etc., who demonstrate on a daily basis that there is patient empowerment, joy, kindness, compassion, and synergy created by a large number of passionate and dedicated survivors and advocates who band together in cyberspace.

• The dedicated service of our U.S. military personnel (and their families), who allow us to rise and sleep under the blanket of freedom which they provide each day through blood, sweat, and tears.

• The roofs over our heads, the food on our tables, the clean water from our faucets, the freedom of speech and religious practice upon which our country was founded, the ability to vote in fair elections, and the simple acts of kindness that we are able to provide to and receive from others.

From our family to yours, let us take this opportunity to wish you a safe and enjoyable Thanksgiving holiday.

FDA Revokes Approval of Avastin Use For Metastatic Breast Cancer; Major U.S. Ovarian Cancer Advocacy Organization Concerned

Today, the U.S. Food and Drug Administration (FDA) Commissioner Hamburg revoked approval of Avastin for treatment of metastatic breast cancer in the U.S. The decision does not impact Avastin’s availability for its approved uses for other cancer types in the U.S. A major U.S. ovarian cancer advocacy organization is concerned that the FDA decision will make it more difficult for ovarian cancer patients to gain access to Avastin.

FDA Revocation of Avastin Approval For Metastatic Breast Cancer

FDA Commissioner Margaret A. Hamburg, M.D., said today she is revoking the agency’s approval of the breast cancer indication for Avastin® (bevacizumab) after concluding that the drug has not been shown to be safe and effective for that use.

Avastin will still remain on the market as an approved treatment for certain types of colon, lung, kidney and brain cancer (glioblastoma multiforme).

“This was a difficult decision. FDA recognizes how hard it is for patients and their families to cope with metastatic breast cancer and how great a need there is for more effective treatments. But patients must have confidence that the drugs they take are both safe and effective for their intended use,” Dr. Hamburg said. “After reviewing the available studies it is clear that women who take Avastin for metastatic breast cancer risk potentially life-threatening side effects without proof that the use of Avastin will provide a benefit, in terms of delay in tumor growth, that would justify those risks. Nor is there evidence that use of Avastin will either help them live longer or improve their quality of life.”

Avastin’s risks include severe high blood pressure; bleeding and hemorrhaging; heart attack or heart failure; and the development of perforations in different parts of the body such as the nose, stomach, and intestines.

Today’s decision, outlined in Dr. Hamburg’s 69-page opinion, involves Avastin used in combination with the cancer drug paclitaxel (Taxol) for those patients who have not been treated with chemotherapy for their form of metastatic breast cancer known as “HER-2 negative.” This indication must now be removed from Avastin’s product labeling.

Dr. Hamburg’s decision is based on an extensive record, which includes thousands of pages submitted to a public docket, data from several clinical trials, and the record from a two-day hearing held in June, 2011.

Avastin was approved for metastatic breast cancer in February 2008 under the FDA’s accelerated approval program, which allows a drug to be approved based on data that are not sufficiently complete to permit full approval. The accelerated approval program provides earlier patient access to promising new drugs to treat serious or life-threatening conditions while confirmatory clinical trials are conducted. If the clinical trials do not justify the continued approval of the drug or a specific drug indication, the agency may revoke its approval. In this case, the accelerated approval was based on promising results from one study that suggested that the drug could provide a meaningful increase in the amount of time from when treatment is started until the tumor grows or the death of the patient.

After the accelerated approval of Avastin for breast cancer, the drug’s sponsor, Genentech (a member of the Roche Group) completed two additional clinical trials and submitted the data from those studies to the FDA. These data showed only a small effect on tumor growth without evidence that patients lived any longer or had a better quality of life compared to taking standard chemotherapy alone – not enough to outweigh the risk of taking the drug.

The FDA’s Center for Drug Evaluation and Research (CDER), which is responsible for the approval of this drug, ultimately concluded that the results of these additional studies did not justify continued approval and notified Genentech that it was proposing to withdraw approval of the indication.

Genentech did not agree with CDER’s evaluation of the data and, following the procedures set out in FDA regulations, requested a hearing on CDER’s withdrawal proposal, with a decision to be made by the FDA Commissioner. That two-day hearing, which took place June 28-29, 2011, included recommendations from the FDA’s Oncologic Drugs Advisory Committee (ODAC), voting 6-0 in favor of withdrawing approval of Avastin’s breast cancer indication. After the hearing, the public docket remained open until August 4, 2011. In an earlier meeting of the ODAC, that committee had voted 12-1 in favor of the removal of the breast cancer indication from the Avastin label.

“FDA is committed to working with sponsors to bring promising cancer drugs to market as quickly as possible using tools like accelerated approval,” Dr. Hamburg said. “I encourage Genentech to consider additional studies to identify if there are select subgroups of women suffering from breast cancer who might benefit from this drug.”

Genentech Response

In a press release issued earlier today, Genentech’s Hal Barron, M.D., chief medical officer and head, Global Product Development, stated:

“We are disappointed with the outcome. We remain committed to the many women with this incurable disease and will continue to provide help through our patient support programs to those who may be facing obstacles to receiving their treatment in the United States. Despite today’s action, we will start a new Phase III study of Avastin in combination with paclitaxel in previously untreated metastatic breast cancer and will evaluate a potential biomarker that may help identify which people might derive a more substantial benefit from Avastin.”

Genentech emphasizes the following points in its press release:

• The FDA Commissioner revoked approval of Avastin for treatment of metastatic breast cancer in the U.S.

• The FDA’s action concludes its review of Avastin’s use for metastatic breast cancer.

• The FDA decision does not impact Avastin’s approved uses for other cancer types in the U.S. or other countries.

• The FDA decision does not impact the approval of Avastin for metastatic breast cancer in more than 80 foreign countries.

• Roche will initiate a new clinical trial of Avastin plus paclitaxel in metastatic breast cancer.

• Genentech will issue a letter to healthcare providers and will also provide them with a letter to distribute to their patients. Both letters will be made available on Genentech’s website.

• Patients with questions or concerns about insurance coverage, or doctors with questions about reimbursement, can call Genentech’s Access Solutions Group at (866)-4- ACCESS.

• Doctors with questions about Avastin can call Genentech’s Medical Communications group at (800) 821-8590.

• The FDA’s action does not impact ongoing clinical trials with Avastin in breast cancer. For more information, please call Genentech’s Trial Information Support Line at (888) 662-6728 or visit clinicaltrials.gov.

Major U.S. Ovarian Cancer Advocacy Organization Concerned About Future Impact of FDA Decision

Karen Orloff Kaplan, MSW, MPH, ScD, Chief Executive Officer, Ovarian Cancer National Alliance

Karen Orloff Kaplan, MSW, MPH, ScD, the Chief Executive Officer for the Ovarian Cancer National Alliance (OCNA), expressed concern that the removal of metastatic breast cancer from the Avastin label could negatively affect women with ovarian cancer, for whom the drug is used “off-label.”  OCNA is one of the most influential advocates for women with ovarian cancer in the United States.

Dr. Kaplan stated:

“Results from three Phase III clinical studies show that Avastin is beneficial for some women with ovarian cancer. We are deeply concerned that the Food and Drug Administration’s decision regarding metastatic breast cancer will make it difficult for women with ovarian cancer to access Avastin, and that patients could be denied insurance coverage for this treatment. The Ovarian Cancer National Alliance will continue our work to ensure that drugs that are useful and medically appropriate are available to women with this disease.”

In the FDA report accompanying her decision, Commissioner Hamburg cited a lack of evidence that Avastin improved overall survival for women with metastatic breast cancer in its decision. “Given how difficult it is to measure overall survival in ovarian cancer clinical trials, we are concerned that today’s ruling may set an unfortunate precedent,” said Dr. Kaplan.

Currently, various national cancer treatment guidelines, such as the National Comprehensive Cancer Network (NCCN) Compendium™, include Avastin as a treatment for ovarian cancer. Despite that fact, the FDA’s decision could prompt a reexamination of industry treatment guidelines by various groups, including the NCCN. The NCCN  is a nonprofit alliance which consists of 21 leading U.S. cancer centers.

Specifically, OCNA is concerned that the FDA Avastin label change, mandated by today’s FDA decision, will lead to restrictions by third party payers, including the U.S. Medicare federal insurance program, who generally reimburse for Avastin when a woman’s cancer has returned. OCNA’s concern may be warranted because Reuters reported earlier today that some healthcare insurers have already started pulling back on Avastin reimbursement coverage for breast cancer.

As of now, according to Reuters, Medicare will continue to pay for Avastin used in the treatment of breast cancer, despite  the FDA’s revocation decision. “Medicare will continue to cover Avastin,” said Don McLeod, a spokesman for the Centers for Medicare and Medicaid Services (CMS). “CMS will monitor the issue and evaluate coverage options as a result of action by the FDA but has no immediate plans to change coverage policies.” The CMS statement may mitigate concerns that patients using the drug would lose critical drug reimbursement insurance coverage in the future.

Sources:

• FDA Commissioner announces Avastin decision — Drug not shown to be safe and effective in breast cancer patients, News Release, United States Food & Drug Administration, November 18, 2011.

• FDA Commissioner Announces Final Decision on Avastin for Metastatic Breast Cancer, Press Release, Genentech, November 18, 2011.

• Ovarian Cancer Advocates Troubled by FDA Decision on Avastin and Breast Cancer, By Staff Editor, HealthNewsDigest.com, November 18, 2011.

• FDA Revokes Approval of Avastin for Breast Cancer, Reuters (U.S. edition), November 18, 2011.

• Medicare to Still Cover Avastin for Breast Cancer, Reuters (U.S. edition), November 18, 2011.

Addtional Information:

• Proposal to Withdraw Approval for the Breast Cancer Indication For Avastin (Bevacizumab) — Decision of the Commissioner, Docket No. FDA 2010-N-0621, U.S. Food & Drug Administration, Department of Health and Human Services, November 18, 2011. [Adobe Reader PDF doc.]

• FDA Commissioner’s Opening Statement from Media Call, U.S. Food & Drug Administration, Department of Health and Human Services, November 18, 2011.

• Questions and Answers: Removing Metastatic Breast Cancer as an Indication from Avastin’s Product Labeling, U.S. Food & Drug Administration, Department of Health and Human Services, November 18, 2011.

• Hearing on Proposal to Withdraw Approval for the Breast Cancer Indication for Bevacizumab (Avastin), U.S. Food & Drug Administration, Department of Health and Human Services, November 18, 2011.

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.