Inaugural World Ovarian Cancer Day: “World Embrace” to Learn, Educate, Fight & Inspire

May 8th, 2013, is the first World Ovarian Cancer Day. On this day, 26 ovarian cancer organizations from 17 countries around the world will unite to educate their communities about ovarian cancer and its symptoms. For women living with the disease, and their families and friends, World Ovarian Cancer Day will build a sense of solidarity in the fight against ovarian cancer.

“LEARN:” Inaugural World Ovarian Cancer Day — May 8, 2013

Ovarian cancer has the lowest survival rate of all gynecologic cancers, and is characterized around the world by a lack of awareness of symptoms and late stage diagnosis.

Today, May 8th, 2013, is the first World Ovarian Cancer Day (WOCD). On this day, ovarian cancer organizations from around the world will unite to educate their communities about ovarian cancer and its symptoms. For women living with the disease, and their families and friends, World Ovarian Cancer Day will build a sense of solidarity in the fight against the disease.

In 2009, representatives from patient organizations working in ovarian cancer around the globe came together for the first time in a two day workshop, to discuss the common issues they faced in their work.

Unlike more common cancers, there are significant challenges as the disease has been largely overlooked and underfunded to this point. Symptoms which are similar to those of less serious illnesses, the absence of an early detection test, and the resulting late diagnosis and poor outcomes means there are few survivors of the disease to become advocates. This initial meeting galvanized the community to begin thinking about what could be accomplished on a global level to begin changing this situation.

By coming together since that first meeting, the group has considered the many gaps in understanding and managing the disease, building awareness in the general public about symptoms and the importance of family history, and increasing funding for research .The idea of a Global Awareness Day for Ovarian Cancer was put forward and embraced by all participants as an important joint international action creating a powerful momentum.

A brand for World Ovarian Cancer Day, “World Embrace,” was developed and launched to the international group in March 2013 in preparation for this important day.

“EDUCATE:” Ovarian Cancer Facts:

Libby’s H*O*P*E* is dedicated to my 26-year old cousin, Elizabeth “Libby” Remick, who died from ovarian cancer in July 2008. Our mission is to educate ovarian cancer survivors and their families, as well as the general public, about ovarian cancer under the principle that “information is power.” The key to a significant reduction in deaths from ovarian cancer is early detection. Early detection is best achieved by having women listen to their bodies for the subtle, yet persistent, early warning signs & symptoms of the disease as described below. Together, we can raise money for a reliable early detection test, and ultimately a cure, for ovarian cancer.

Please take time to educate yourself with respect to the important ovarian cancer awareness facts provided below.

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

–In 2012, the American Cancer Society (ACS) estimates that there will be approximately 22,280 new ovarian cancer cases diagnosed in the U.S. ACS estimates that 15,550 U.S. women will die from the disease, or about 43 women per day. The loss of life is equivalent to 28 Boeing 747 jumbo jet crashes with no survivors every year.

–Ovarian cancer is not a “silent” disease; it is a “subtle” disease. Recent studies indicate that some women may experience persistent, nonspecific symptoms, such as (i) bloating, (ii) pelvic or abdominal pain, (iii) difficulty eating or feeling full quickly, or (iv) urinary urgency or frequency. Women who experience such symptoms daily for more than a few weeks should seek prompt medical evaluation.

–Ovarian cancer can afflict adolescent, young adult, and mature women.

–Pregnancy and the long-term use of oral contraceptives reduce the risk of developing ovarian cancer.

–Women who have had breast cancer, or who have a family history of breast cancer or ovarian cancer may have increased risk. Inherited mutations in BRCA1/BRCA2 genes increase risk. Women of Ashkenazi Jewish ancestry are at higher risk for BRCA gene mutations.

–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 is used to detect cervical cancer, not ovarian cancer. However, the combination of a thorough pelvic exam, transvaginal ultrasound, and a blood test for the tumor marker CA125 may be offered to women who are at high risk of ovarian cancer and to women who have persistent, unexplained symptoms like those listed above.

–If diagnosed at the localized stage, the 5-year ovarian cancer survival rate is 92%; however, only about 19% of all cases are detected at this stage, usually fortuitously during another medical procedure.

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

Please help us spread the word about the early warning signs & symptoms of ovarian cancer and raise money for ovarian cancer research. The life you save may be your own or that of a loved one.

“FIGHT:” The “Holy Trinity” of Major U.S. Ovarian Cancer Organizations

There are three major U.S. ovarian cancer organizations that are working to increase ovarian cancer awareness, and/or raise money to fight the disease. They are listed below. Please consider making a donation to one of these critically important nonprofit organizations.

• Ovarian Cancer Research Fund

The Ovarian Cancer Research Fund (OCRF) is the largest independent organization in the U.S. that is dedicated exclusively to funding ovarian cancer research– and to finding a cure. Through its three research programs, OCRF funds many of the best researchers and the most innovative projects.

Since 1998, OCRF has awarded 63 leading medical centers 195 grants for ovarian cancer research: an investment totaling over $50 million. OCRF researchers are taking on ovarian cancer from many angles:

– Developing innovative strategies for early detection;

– Discovering genetic polymorphisms that increase risk for ovarian cancer;

– Understanding the underlying genetics and molecular biology of ovarian cancer;

– Identifying new, better targets for treatment;

– Determining how to super-charge a woman’s immune response to better fight ovarian cancer; and

– Deciphering how and why ovarian cancer spreads, and how to stop it.

You can click here to make a donation to OCRF through the Libby’s H*O*P*E*’s donation page.

• Ovarian Cancer National Alliance

The Ovarian Cancer National Alliance (OCNA) is one of the foremost advocates for women with ovarian cancer in the U.S. To advance the interests of women with ovarian cancer, OCNA advocates at a national level for increases in research funding for the development of an early detection test, improved health care practices, and life-saving treatment protocols. OCNA also educates health care professionals and raises public awareness of the risks and symptoms of ovarian cancer.

To make a donation to OCNA, click here.

• National Ovarian Cancer Coalition

The mission of the National Ovarian Cancer Coalition (NOCC) is to raise awareness and promote education about ovarian cancer. NOCC is committed to improving the survival rate and quality of life for women with ovarian cancer.

Through national programs and local Chapter initiatives, the NOCC’s goal is to make more people aware of the early symptoms of ovarian cancer. In addition, the NOCC provides information to assist the newly diagnosed patient, to provide hope to survivors, and to support caregivers.

To make a donation to NOCC, click here.

“INSPIRE:” Everyday Heroes in the Fight Against Ovarian Cancer.

Nearly a quarter million women are diagnosed with ovarian cancer every year around the world, and the disease also affects their families and friends. Please take time to visit the WOCD website and read inspirational stories about survivors, volunteers, and family members who are overcoming ovarian cancer, as well as the endeavors people are taking on to raise awareness about the disease.

At Libby’s H*O*P*E*, we are amazed each and every day by the inspirational ovarian cancer survivors and family members that we hear about, correspond with, or meet. The stories below represent a small sample of incredible individuals who have successfully fought the disease, as well as those who are currently fighting the disease with courage and grace. There are also stories about women who have died from ovarian cancer, but contributed to ovarian cancer awareness in a unique and special way during life. In addition, there are stories about doctors, advocates, and other inspirational individuals who are clearly making a difference in the fight against the disease.

– “Bald is Beautiful,” March 20, 2008.

– “Patty Franchi Flaherty Loses Battle to Ovarian Cancer, But Deserves a Long Standing Ovation,” August 19, 2008.

– “Oscar Winner Kathy Bates Is an Inspirational Ovarian Cancer Survivor,” February 25, 2009.

– “Rare Form of Ovarian Cancer Not Getting Inspirational 13 Yr. Old Down; You Can Help!,” February 26, 2009.

– “Meet Laurey Masterton, 20-Year Ovarian Cancer Survivor Extraordinaire,” March 20, 2009.

– “The Rock Band ‘N.E.D.’: Their Medical Skills Save Many; Their Music Could Save Thousands,” March 29, 2009.

– “A Wish To Build A Dream On,” May 3, 2009.

– “Husband’s Love For Wife Inspires A 9,000 Mile Bike Trek To Raise Money For Ovarian Cancer Awareness & Cancer Prevention,” May 14, 2009.

– “Gloria Johns Was Told ‘Ovarian Cancer Patients Don’t Live Long Enough … To Have Support Groups;’ She Proved Otherwise,” June 5, 2009.

– “Vox Populi:* How Do Your Define “Tragedy?“, January 22, 2010.

– “Smile, Open Your Eyes, Love and Go On,” July 28, 2010.

– “PBS Documentary, ‘The Whisper: The Silent Crisis of Ovarian Cancer,’” September 21, 2010.

– “Determined Teen Loses Ovarian Cancer Battle, But Her Courage Inspires An Entire Community,” December 28, 2010.

– “Mrs. Australia Quest Finalist Veronica Cristovao Is Raising Ovarian Cancer Awareness ‘Down Under’”, February 28, 2011.

– “Whither Thou Goest, I Will Go …”, July 28, 2012.

– “Crowd Funding:” Paying Medical Bills With a Little Help From Your Friends (and Strangers Too!), January 17, 2013.

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For more information on World Ovarian Cancer Day visit: www.ovariancancerday.org

Facebook: www.facebook.com/WorldOvarianCancerDay

Twitter: @OvarianCancerDY

Pinterest: @OvarianCancerDY

Each participating country is linked through the dedicated website which has been established for World Ovarian Cancer Day. To find out more about activities in each country, please contact the local organization directly through the website at http://www.ovariancancerday.org/get-involved/

“Adoptive T-Cell” Immunotherapy Shows Activity Against Advanced Ovarian Cancer in Phase I Study

In a new study, researchers from the Perelman School of Medicine at the University of Pennsylvania School of Medicine show that a two-step personalized immunotherapy treatment — a dendritic cell vaccine using the patient’s own tumor followed by adoptive T cell therapy — triggers anti-tumor immune responses in advanced ovarian cancer patients.

Most ovarian cancer patients are diagnosed with late stage disease that is unresponsive to existing therapies. In a new study, researchers from the Perelman School of Medicine at the University of Pennsylvania School of Medicine show that a two-step personalized immunotherapy treatment — a dendritic cell vaccine using the patients’ own tumor followed by adoptive T cell therapy — triggers anti-tumor immune responses in these type of patients. Four of the six patients treated in the phase I trial responded to the therapy, the investigators report this month in OncoImmunology.

“What we proved in this study is that this is a safe treatment strategy,” says co-first author Lana Kandalaft, PharmD, MTR, Ph.D., research assistant professor of Obstetrics and Gynecology and director of clinical development in the Ovarian Cancer Research Center. “It is a walk in the park for patients, especially compared to standard chemotherapies and surgical treatments for ovarian cancer – literally, some patients left the clinic and went for a walk in a nearby park after their treatment.”

The findings follow research by the study’s senior author, George Coukos, M.D., Ph.D., director of the Ovarian Cancer Research Center at Penn, who showed in 2003 that women whose ovarian tumors were infiltrated by healthy immune cells, called T cells, tended to live longer than women whose tumors were devoid of T cells. That observation and other subsequent ones suggest the patient’s immune system is trying to fight off the disease but can’t quite muster the strength to beat it. Therefore, investigators have been trying to find ways using patients’ own tumor cells to boost the immune system’s power.

Adoptive T-Cell Therapy Approach

In the first segment of the study, the University of Pennsylvania researchers prepared an individualized dendritic cell vaccine for each ovarian cancer patient. (Photo Credit: Penn Medicine)

In the current study, Coukos, Kandalaft, co-first author Daniel J. Powell Jr., PhD, research assistant professor of Pathology and Laboratory Medicine, and colleagues treated six women with advanced ovarian cancer in a two-staged immunotherapy protocol in which they utilized a dendritic cell vaccine created from tissue in the patients’ own tumor, which was stored at time of surgery. All of these women’s cancers had progressed on standard of care chemotherapy.

In the first segment of the study, the team prepared an individualized dendritic cell vaccine for each patient. They harvested dendritic cells from each patient using apheresis, the same process volunteers go through when they donate platelets or other blood products such as those collected for stem cell transplants. Kandalaft and colleagues then exposed each patient’s dendritic cells to tumor extract produced from the woman’s ovarian cancer tumor, which teaches the dendritic cells who the enemy is. After this priming, the investigators vaccinated each patient with her own dendritic cells and gave them a combination chemotherapy regimen consisting of bevacizumab (Avastin) and  metronomic cyclophosphamide. Because dendritic cells are like the generals of the immune system, they then induce other immune cells to take up the fight.

Of the six advanced ovarian cancer patients who received the dendritic cell vaccine, four patients developed an anti-tumor immune response, indicating that the approach was working. One of those patients had no measurable disease at study entry because all of it had been successfully removed during surgery. She remains in remission today, 42 months following vaccine treatment. The remaining three who had an immune response to the vaccine still had residual disease and went on to the second segment of treatment.

In the second segment of the study, T cells were harvested from the ovarian cancer patients, grown in the laboratory, thereby expanding their numbers exponentially, and then were reintroduced into each patient after she underwent a lymphodepleting chemotherapy regimen. (Photo Credit: Penn Medicine)

In the second segment of the study, the team harvested T cells from each of the three women mentioned above. Using a technique developed at Penn, the researchers grew the cells in the laboratory, expanding their numbers exponentially, and then reintroduced them into each patient after she underwent a lymphodepleting chemotherapy regimen. Because the T cells had already been trained by the dendritic cell vaccine to attack the tumor cells, the adoptive T cell transfer amplifies the anti-tumor immune response.

Two of the women showed a restored immune response after the T cell transfer. One of the women continued to have stable disease, whereas the other had a complete response to the therapy.

The researchers say it is too early to say whether this type of therapy will be effective in a large number of ovarian cancer patients, but the early results are promising. First, and foremost, she notes, the two-step approach appears safe and well tolerated by the patients. Additionally, the team saw a correlation in both treatment steps between immune responses and clinical benefit, suggesting that it is, in fact, the immune response that is holding the disease in check.

With these encouraging results in hand, the team has opened a larger trial (UPCC-19809 & UPCC-26810; clinical trial protocols listed below) in which they have already enrolled about 25 women and aim for up to 30 more. The new protocol uses an improved vaccine platform and an optimized adoptive T cell transfer protocol. The prinicipal investigator of this study is Janos Tanyi, MD, PhD.

“Large clinical trials have shown that intensifying chemotherapy doesn’t improve outcomes for women with advanced ovarian cancer,” Coukos says. “So we need to explore other avenues. We think the combinatorial approach of both immune and chemotherapy is the way to go.”

Other co-authors from Penn include Cheryl L. Chiang, Janos Tanyi, Sarah Kim, Kathy Montone, Rosemarie Mick, Bruce L. Levine, Drew A. Torigian, and Carl H. June. Co-author Marnix Bosch is from Northwest Biotherapeutics in Bethesda, Maryland.

This study was supported by National Cancer Institute Ovarian SPORE grant P01-CA83638, National Institution of Health R01FD003520-02, and the Ovarian Cancer Immunotherapy Initiative. 

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Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

The Perelman School of Medicine is currently ranked #2 in U.S. News & World Report’s survey of research-oriented medical schools. The School is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $479.3 million awarded in the 2011 fiscal year.

The University of Pennsylvania Health System’s patient care facilities include: The Hospital of the University of Pennsylvania — recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital — the nation’s first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2011, Penn Medicine provided $854 million to benefit our community.

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Sources:

Kandalaft L, Powell D, Chiang C, et. al. Autologous lysate-pulsed dendritic cell vaccination followed by adoptive transfer of vaccine-primed ex vivo co-stimulated T cells in recurrent ovarian cancer. OncoImmunology 2013; 2:e22664; http://dx.doi.org.

Two-Step Immunotherapy Attacks Advanced Ovarian Cancer, Penn Medicine Researchers Report, Penn Medicine, Press Release, January 31, 2013.

Closed Clinical Trial Protocols (two study segments discussed above):

Study Segment One: A Phase I Clinical Trial of Autologous Dendritic Cell Vaccine Loaded With Autologous Tumor Cell Lysate for Recurrent Ovarian or Primary Peritoneal Cancer; ClinicalTrials.gov Identifier: NCT00683241; UPCC ID: 11807.

Study Segment Two: A Phase-I/II Randomized Trial of Maintenance Vaccination Combined With Metronomic Cyclophosphamide w/wo Adoptive Transfer of CD3/CD28-CoStimulated T-Cells for Recurrent Ovarian or Primary Peritoneal Cancer Previously Vaccinated DCVax-L; ClinicalTrials.gov Identifier: NCT00603460; UPCC ID: 10808

Open Clinical Trial Protocols (enrolling new patients, as of this writing):

A Pilot Clinical Trial of Dendritic Cell Vaccine Loaded With Autologous Tumor for Recurrent Ovarian, Primary Peritoneal or Fallopian Tube Cancer;  ClinicalTrials.gov ID: NCT01132014;  UPCC ID: 19809. [currently recruiting patients]

A Phase-1 Trial of Adoptive Transfer of Vaccine-Primed CD3/CD28-Costimulated Autologous T-Cells Combined With Vaccine Boost and Bevacizumab for Recurrent Ovarian Fallopian Tube or Primary Peritoneal Cancer Previously Vaccinated With Autologous Tumor Vaccine; ClinicalTrials.gov ID: NCT01312376;  UPCC ID: 26810. [currently recruiting patients]

Related Libby’s H*O*P*E* Articles:

Gene Transfer Therapy Destroys Tumors in Chronic Lymphocytic Leukemia Patients; Holds Promise For Ovarian Cancer, by Paul Cacciatore, August 11, 2011.

Penn’s Genetically Modified T Cells Create Antitumor Effect In Mice With Folate Positive Ovarian Cancer; Clinical Trial Pending, by Paul Cacciatore, August 17, 2011.

World Cancer Day 2013: Dispelling Myths & Misconceptions About “The Enemy Within”

1.5 million premature cancer deaths could be prevented each year if targets set to reduce non-communicable diseases are met by 2025.  Today, on World Cancer Day, the Union for International Cancer Control and the International Agency for Research on Cancer reveal the real life impact of achieving this goal.

World Cancer Day 2013

“… 1.5 million people saved from an early death due to cancer is equal to the entire populations of Philadelphia, Auckland, Barcelona or Maputo each and every year.”

World Cancer Day is the one initiative under which the entire world can unite in the fight against the global cancer epidemic.It takes place every year on February 4th. World Cancer Day aims to save millions of preventable deaths each year by raising awareness and education about cancer, and pressing governments and individuals across the world to take action against the disease.

World Cancer Day is an initiative of the Union for International Cancer Control (UICC), a leading international non-governmental organization dedicated to the prevention and control of cancer worldwide. Founded in 1933 and based in Geneva, UICC’s growing membership of over 765 organizations across 155 countries, features the world’s major cancer societies, ministries of health, research institutes, treatment centers, and patient groups. Additionally, the organization is a founding member of the NCD Alliance, a global civil society network that now represents almost 3,000 organizations in 170 countries.

Target “25 by 25:” Reduce 25% of Premature Non-Communicable Disease Deaths by 2025

The UICC and the International Agency for Research on Cancer (IARC) today announced that 1.5 million lives which would be lost to cancer, could be saved each year if decisive measures are taken to achieve the World Health Organization’s (WHO) “25 by 25″ target; to reduce premature deaths due to non-communicable diseases (NCDs), including cancer, by 25% by 2025.

Currently, 7.6 million people die from cancer worldwide every year, out of which, 4 million people die prematurely (aged 30 to 69 years). So unless urgent action is taken to raise awareness about the disease and to develop practical strategies to address cancer, by 2025, this is projected to increase to an alarming 6 million premature cancer deaths per year.

“The estimate of 1.5 million lives lost per year to cancer that could be prevented must serve to galvanize our efforts in implementing the WHO’s ‘25 by 25’ target,” said Dr.  Christopher Wild, Director of IARC. “There is now a need for a global commitment to help drive advancements in policy and encourage implementation of comprehensive National Cancer Control Plans. If we are to succeed in this, we have a collective responsibility to support low- and middle-income countries who are tackling a cancer epidemic with insufficient resources.”

The 1.5 million lives lost per year represent 25% of the estimated 6 million premature cancer deaths that will occur by 2025, and the 6 million figure is itself based on population projections of current numbers and aging.

“Cancer — Did You Know?”

On World Cancer Day, UICC and its members are urging the public and governments alike to speak out with one voice to dispel damaging myths and misconceptions on cancer. Under the theme “Cancer – Did you know?” individuals and communities are encouraged to shed light on four key cancer “myths” and the corresponding “truth” via the UICC World Cancer Day Facebook App.

Myth #1: Cancer is just a health issue.

Truth #1: Cancer is not just a health issue. It has wide-reaching social, economic, development and human rights implications.

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Myth #2: Cancer is primarily a disease of the wealthy, elderly, and developed countries.

Truth #2: Cancer is a global epidemic, affecting all ages and socio-economic groups, with developing countries bearing a disproportionate burden.

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Myth #3: Cancer is a death sentence.

Truth #3: Many cancers that were once considered a death sentence can now be cured and for many more people their cancer can now be treated effectively.

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Myth #4: Cancer is my fate.

Truth #4: With the right strategies, at least 30% of cancer cases can be prevented based on current knowledge.

———-

Mr. Cary Adams, UICC Chief Exective Officer said:

“This World Cancer Day UICC, its members and partners urge everyone from individuals to governments to take a stand against damaging myths on cancer. By truly understanding this deadly disease, governments can develop appropriate strategies to reduce premature deaths and reach the WHO ‘25 by 25’ goal. The figures today announced by IARC and UICC reveal the fundamental human value of achieving this target. 1.5 million people saved from an early death due to cancer is equal to the entire populations of Philadelphia, Auckland, Barcelona or Maputo each and every year.”

What Can You Do?

In 2008, UICC developed the World Cancer Declaration as a tool to help bring the growing cancer crisis to the attention of government leaders and health policymakers. The 11 Declaration targets, designed to significantly reduce the global cancer burden by 2020, have served as the basis for UICC recommendations to the WHO. This year’s goal — #5 Declaration target — is to dispel damaging cancer myths and misconceptions. The Declaration, with more than half a million signatories, has also been instrumental in generating political will for cancer control targets both at the United Nations and grassroots levels. In close collaboration with the NCD Alliance, UICC played a key role recently in securing WHO’s global health target of a 25% reduction in premature deaths from NCDs by 2025 (known as “25 by 25”), at the World Health Assembly in May 2012 – demonstrating the important role advocacy plays in the global flight against cancer.

To sign the World Cancer Declaration, click here.

To download the World Cancer Day Facebook App, and play your part in reducing the unacceptable burden of cancer, visit https://apps.facebook.com/world_cancer_day.

Review and circulate the cancer truth fact sheets hyperlinked above under the “Cancer — Did You Know?” section of this article.

For more ideas on how you can get involved and take local action against the global crisis of cancer, visit worldcancerday.org.

Understanding Cancer:  ”The Enemy Within” Documentary

In the documentary posted below, Vivienne Parry OBE tells the incredible story of our fight against cancer over the last 50 years. Through the eyes of scientists, researchers, and patients, we see how far we have come and how far we have yet to go, including contributions from Professor Robert Weinberg, Professor Umberto Veronesi, Lord Ara Darzi, Cancer Research UK, David Nathan, M.D., Brian Druker, M.D., and many more.

The film is a non-commercial, editorially independent piece of work which has been supported by Cancer Research UK and funded by an educational grant from Roche. The purpose is to educate and inform those who are affected by cancer. It’s now freely available to all who may want to use it, so please feel free to embed on your own websites and share as you see fit.

“Crowd Funding:” Paying Medical Bills With a Little Help From Your Friends (and Strangers Too!)

An interesting article appearing in USA Today on January 14, written by Cheryl Alkon, describes the use of “crowd funding” to assist individuals who may be experiencing tough financial times — or even bankruptcy — due to, among other things, medical costs, including those incurred to treat cancer.

What is “Crowd Funding?”

The term “crowd funding” describes the collective effort of individuals who network and pool their money, generally through the Internet, to support efforts initiated by other people or organizations. For example, crowd funding can be used to support disaster relief, citizen journalism, political campaigns, startup company funding, movie or software development, and scientific research.

Crowd funding is even taking on national significance through enacted federal legislation. In April 2012, President Obama signed the JOBS (Jumpstart Our Business Startups) Act, which enables entrepreneurs, start-ups, and small businesses to raise funds and gather investors through equity crowd funding.

An interesting article appearing in USA Today on January 14, written by Cheryl Alkon, describes the use of crowd funding to assist individuals who may be experiencing tough financial times — or even bankruptcy — due to, among other things, medical costs, including those incurred to treat cancer. The crowd funding websites listed by Alkon include: the Human Tribe Project (humantribeproject.com), GiveForward (giveforward.com), FundRazr (fundrazr.com), and GoFundMe (gofundme.com).

It is estimated that $2.8 billion was raised by all types of crowdfunding websites in 2012.

In an era when social media and networking reign supreme, most individuals have “friends,” and even “friends of friends.” At this point, you should be thinking about The Beatles song entitled, A Little Help From My Friends, which the group recorded on their Sgt. Pepper’s Lonely Hearts Club Band album in 1967. Or perhaps, you prefer Joe Cocker’s cover version of the song, which he sang at the Woodstock Music Festival in 1969. But, I digress. So, let’s turn to a great example of crowding funding used to support medical costs.

The Genesis of the Human Tribe Project

The Human Tribe Project Leadership Team: (left-to-right) Ryan Foutz, Jaclyn Foutz, Matt Foutz, and Steve Bever.

The concept of crowd funding within the context of cancer treatment is best understood through the genesis of The Human Tribe Project.

In early 2008, Jaclyn Foutz learned that her longtime friend, Kindra McLennan, had been diagnosed with a rare form of cervical cancer. Not knowing how to help Kindra, who lived 1,500 miles away, Jaclyn did what anyone thirty-something would do: she turned to Google®.

Her search turned up various websites listing ways to help support and encourage a friend through cancer, and of those, some even suggested fundraising ideas. Realizing that they could not be there to hold Kindra’s hand through the chemotherapy and radiation, Jaclyn and her friends decided to raise money for Kindra and her husband to relieve the financial burden associated with her cancer treatment. Jaclyn identified websites suggesting fundraising options, but all seemed too local and small in scope to have the kind of impact that she and her friends wanted. At the time, Jaclyn’s husband, Ryan Foutz, his brother, Matt Foutz, and Ryan’s childhood friend, Steve Bever, owned a wholesale jewelry company. They donated turquoise beads, and Jaclyn and her friends sold turquoise necklaces in support of Kindra. They sold the necklaces in-person to friends, relatives and coworkers, and by e-mail to people in Kindra’s support network all across the country.

The project was a huge success; they sold 350 necklaces and raised $10,000. They were inspired by the breadth of Kindra’s network of friends and the willingness of complete strangers to buy the necklaces.

Initially, Kindra refused to take handouts from her friends and family; however, when she knew her friends and family were receiving a necklace in return for their monetary donation, her concerns were alleviated. And, when Kindra saw everyone from her best friend to her chemotherapy nurse wearing the necklaces, she felt an emotional support as great as the financial support that she had received.

After extensive research, Jaclyn and Ryan learned that there were no resources available to do what they did on a larger, commercial scale. They found companies selling products in an effort to raise money for non-profits, foundations, or research institutions, but none raised money directly for individuals during their time of need.

During their research process, they were astonished to learn about the financial burden that individuals suffering from an illness often face. For example, with respect to breast cancer alone, it is estimated that out-of-pocket expenditures and lost-income costs for women with insurance coverage average $1,455.00 per month. The majority of those out-of-pocket costs are related to co-payments, hospitalizations, and specialist visits.

In 2006, twenty-five percent of cancer patients reported that they had to use all or most of their savings to deal with cancer treatment costs. Approximately fifty percent of all personal bankruptcies filed in the U.S. are filed due to medical expenses. Also, researchers have found that there is a strong connection between emotional support and healthcare outcomes. Jaclyn and Ryan found these statistics astounding; there was a better way to aid individuals and enhance the benefits of strong support networks.

Through all of this, Jaclyn, Ryan, Matt, and Steve saw firsthand the power of the humanitarian spirit and how that spirit connects us all. It was from this experience that Human Tribe Project was born.

Ultimately, Kindra McLennan used some of the funds raised on the website to take a trip to Las Vegas for her 30th birthday, four months before she died. “If that’s what you feel you need to use the money for, that’s one of the things you can do when you know the people who are donating to you,” Jaclyn Foutz says. The Human Tribe Project website launched  in early 2009, six months after McLennan’s death.

Not only were Kindra’s friends and family able to raise approximately $10,000 on her behalf, but Kindra could see their love and support in every necklace that was worn. The Human Tribe Project website is dedicated to Kindra’s memory.

After helping establish the Human Tribe project, Matt Foutz never anticipated using the service for his own family. Two years ago, Mathew’s daughter Mia was diagnosed with a brain tumor, called a “medulloblastoma,” at the age of five. Mia received surgery, months of chemotherapy, and radiation treatment, the net result of which was permanent memory, mobility and endocrine issues. Through crowd funding, Matthew Foutz has already raised $11,520 for Mia.

Thoughts From Those In the Field

The USA Today article cites several individuals who are actively involved, directly or indirectly, in the field of crowd funding.

Catherine Chapman, a philanthropic consultant with Fullanthropy, a Louisville, Ky., consulting firm that advises non-profits on charitable best practices said:

Crowd funding is doing what has always been done, but taking the technology we have to make it viral. People give on these sites often because they have been asked to do so by a friend or a friend of a friend. The personal element is a lot more compelling than sending a check to a charity. Doing that is anonymous and you can’t relate, but if it’s your friend who has cancer, you want to help.”

Daryl Hatton, the founder and CEO of FundRazr, said:

“People know who they are donating to, but one of the big surprises is that people saw how many complete strangers were donating to them. The message has to really resonate with your friends, or else it won’t go anywhere. If you don’t get that social proof, then people don’t get donations. Our natural skepticism kicks in, and they hold back on hitting that button.”

According to the USA Today article, it appears that scams are rare. ”Scammers tend to lack social-media followings, as they don’t want to identify themselves,” said Hatton. “Those with integrity have networks. To give you scale, approximately one in 5,000 medical FundRazrs get shut down.”

In the end, a cancer patient can use a crowdfunding site to tell his or her story about why money is needed, using blogs and updates to keep potential donors informed. Most websites collect donations and forward them directly to the person in need. The websites can take out a small portion of the donation for administrative and other costs, which can range from 5%-20% of funds raised. It is important to note that most crowd funding websites are not tax-exempt, non-profit organizations, and therefore, donations are not considered tax-deductible.

The USA Today article provides a few common sense tips to those who may be interested in crowd funding: (i) perform thorough due diligence on various websites beyond looking for a nice appearance (i.e., evaluate news stories, customer reviews, complaints,  etc.); (ii) research online tips for writing a compelling narrative about yourself and the need for money; (iii) give frequent updates (as most blog writers learn quickly); and (iv) know that fundraising is time-consuming, but realize that you are your own best advocate.

There is a saying that “to the world you may only be one person, but to one person you may be the world.” For those of you who may be thinking about helping a cancer survivor through crowd funding, keep in mind that “grand” opportunities to help others seldom arise, but small, yet critical, opportunities surround us everyday.

Sources:

“Crowdfunding” sites pay medical bills, raise hopes, written by Cheryl Alkon, USA Today, January 14, 2013.

“Company Background,” Media Packet, The Human Tribe Project, www.humantribeproject.com.

ENMD-2076 Monotherapy Demonstrates Anti-Cancer Activity in Recurrent, Platinum-Resistant Ovarian Clear Cell Carcinoma

An Aurora A/angiogenic kinase inhibitor named “ENMD-2076″ demonstrated anti-cancer activity in recurrent, platinum-resistant epithelial ovarian cancer patients, including three patients with a difficult-to-treat subtype of the disease referred to as “clear cell carcinoma.”

An Aurora A/angiogenic kinase inhibitor named “ENMD-2076” demonstrated anti-cancer activity in recurrent, platinum-resistant epithelial ovarian cancer patients, including three patients with a difficult-to-treat subtype of the disease referred to as “clear cell carcinoma.” The trial drug results were reported in connection with a phase II clinical trial testing of ENMD-2076. The findings associated with ENMD-2076 were published in the January 2013 edition of the European Journal of Cancer.

ENMD-2076 is an orally-active, Aurora A/angiogenic kinase inhibitor with a unique kinase selectivity profile and multiple mechanisms of action. ENMD-2076 has been shown to inhibit a distinct profile of angiogenic tyrosine kinase targets in addition to the Aurora A kinase. Aurora kinases are key regulators of mitosis (cell division), and are often over-expressed in human cancers. ENMD-2076 also targets the VEGFR, Flt-3 and FGFR3 kinases which have been shown to play important roles in the pathology of several cancers.

The phase II trial was an open-label, single-arm Phase II study of single agent ENMD-2076 taken daily (orally). The study enrolled 64 patients, and the progression-free survival (PFS) rate at 6 months was 22%, with a median time-to-progression of 3.6 months. The median number of prior treatment regimens per patient was two. The most common adverse events were fatigue, hypertension and diarrhea, with the most significant events being hypertension and fatigue. Unfortunately, none of the markers of mitotic index or angiogenesis evaluated in the archival tissue samples obtained were predictive of greater benefit or resistance to ENMD-2076 treatment.

Based on the foregoing results, the clinical investigators concluded that ENMD-2076 possesses anti-cancer activity in recurrent, platinum-resistant ovarian cancer, and they observed  toxicities were similar to other protein kinase inhibitors. The clinical investigators also noted that additional studies with ENMD-2076 are warranted, especially in combination with active chemotherapeutic agents in platinum-resistant patients. The investigators added that further work to determine appropriate biomarkers for ENMD-2076 should be incorporated into new clinical studies.

The co-authors of the article include clinical investigators from the Memorial Sloan-Kettering Cancer Center, Indiana University Simon Cancer Center, University of Colorado, and University of Chicago in the U.S., as well as the Princess Margaret Hospital and Campbell Family Institute for Cancer Research in Toronto, Canada.

Ursula A. Matulonis, M.D., Medical Director, Gynecologic Oncology, Dana-Farber Cancer Institute

Lead study author Dr. Ursula A. Matulonis, who is the medical director of Gynecologic Oncology at the Dana-Farber Cancer Institute, commented on the publication as follows:

“Epithelial ovarian cancer represents the 4th leading cause of cancer deaths among women in the United States. There is unmet medical needs to develop new drugs with fewer side effects and/or better efficacy to improve the quality and duration of life of the patients, especially those whose cancer is resistant to platinum treatment.

ENMD-2076 is a novel small molecule kinase inhibitor with unique combination of mechanisms of action that involve inhibition of several pathways key to tumor growth and survival including angiogenesis, proliferation, and the cell cycle. Based on pre-clinical and Phase 1 clinical studies of ENMD-2076, we believed that the drug candidate may play a role in fitting some of the unmet medical needs. This Phase 2 trial further demonstrates the anti-cancer activity of ENMD-2076 in yet a difficult to treat patient population of platinum-resistant ovarian cancer with tolerable side effects.”

Notably, Dr. Matulonis also commented on the anti-cancer activity of ENMD-2076 in three ovarian clear cell carcinoma patients as follows:

“ENMD-2076 also showed anti-cancer activities in patients with clear cell carcinoma [CCC], a histological subtype considered as chemo-resistant. Two of three [CCC] patients recruited had longer PFS than the median with one patient in stable disease for over two years. As recent reports suggest VEGF is frequently expressed in clear cell cancers, this subtype might be particularly responsive to therapies that incorporate VEGF inhibition. Further clinical evaluations of ENMD-2076 may therefore be warranted in this patient subset either as a single agent or in combinations.” [emphasis added]

Ken Ren, Ph.D., EntreMed’s Chief Executive Officer, further commented:

“We are very pleased and honored to have this Phase 2 trial data published in such an esteemed journal. This is a further endorsement of the global medical and science community on the clinical and scientific value of ENMD-2076 in ovarian cancer treatment. We truly believe that ENMD-2076 may potentially offer unique and competitive advantages for unmet medical needs in such difficult to treat oncology indications including platinum-resistant and/or clear cell ovarian cancer in improving the patients’ quality and duration of life. We are committed to the global clinical development of ENMD-2076 for cancer patients who might benefit from its therapy. With the support of clinical investigators like Dr. Matulonis, their commitment and dedication, and the support from our long term shareholders, we are confident that we can achieve our goal.”

About EntreMed

EntreMed, Inc. is a clinical-stage pharmaceutical company employing a drug development strategy primarily in the United States and China to develop targeted therapeutics for the global market. Its lead compound, ENMD-2076, a selective angiogenic kinase inhibitor, has completed several Phase 1 studies in solid tumors, multiple myeloma, and leukemia, and is currently completing a multi-center Phase 2 study in ovarian cancer. EntreMed, Inc. recently initiated a dual-institutional Phase 2 study of ENMD-2076 in triple-negative breast cancer. Additional information about EntreMed is available on the Company’s web site at www.entremed.com.

About ENMD-2076

ENMD-2076 is an orally-active, Aurora A/angiogenic kinase inhibitor with a unique kinase selectivity profile and multiple mechanisms of action. ENMD-2076 has been shown to inhibit a distinct profile of angiogenic tyrosine kinase targets in addition to the Aurora A kinase. Aurora kinases are key regulators of mitosis (cell division), and are often over-expressed in human cancers. ENMD-2076 also targets the VEGFR, Flt-3 and FGFR3 kinases which have been shown to play important roles in the pathology of several cancers. ENMD-2076 has shown promising activity in Phase 1 clinical trials in solid tumor cancers, leukemia, and multiple myeloma. ENMD-2076 is currently completing a Phase 2 trial for ovarian cancer. EntreMed, Inc. recently initiated a dual-institutional Phase 2 study of ENMD-2076 in triple-negative breast cancer.

ENMD-2076 received orphan drug designation from the United States Food and Drug Administration (FDA) for the treatment of ovarian cancer, multiple myeloma and acute myeloid leukemia (AML). In the United States, the Orphan Drug Act is intended to encourage companies to develop therapies for the treatment of diseases that affect fewer than 200,000 people in this country. Orphan drug designation provides seven years of market exclusivity that begins once ENMD-2076 receives FDA marketing approval. It also provides certain financial incentives that can help support the development of ENMD-2076.

Citation:

Matulonis UA, Lee J, Lasonde B, et. al. ENMD-2076, an oral inhibitor of angiogenic and proliferation kinases, has activity in recurrent, platinum resistant ovarian cancer. Eur J Cancer. 2013 Jan;49(1):121-31.doi:10.1016/j.ejca.2012.07.020. PubMed PMID: 22921155.

Additional Source:

Dana-Farber Cancer Institute’s Ursula A. Matulonis, M.D. Article on EntreMed’s ENMD-2076 Published in the European Journal of Cancer, EntreMed, Inc. Press Release, Sept. 6, 2012.

ENMD-2076 Phase II Ovarian Cancer Clinical Trial Protocol Summary:

A Phase 2 Study of Oral ENMD-2076 Administered to Patients With Platinum Resistant Ovarian Cancer, ClinicalTrials.gov Identifier: NCT01104675 (study ongoing, but not recruiting patients).

Glimmer of Hope: Johns Hopkins Uses Pap Smear Test Cervical Fluid to Detect Ovarian & Endometrial Cancers

Using cervical fluid obtained during routine Pap tests, scientists at the Johns Hopkins Kimmel Cancer Center have developed a test to detect ovarian and endometrial cancers. The investigators note that larger-scale studies are needed prior to clinical use on women. 

Using cervical fluid obtained during routine Pap tests, scientists at the Johns Hopkins Kimmel Cancer Center have developed a test to detect ovarian and endometrial cancers. Results of the experiments are published in the January 9 issue of the journal Science Translational Medicine.

In a pilot study, the “PapGene” test, which relies on genomic sequencing of cancer-specific mutations, accurately detected all 24 (100 percent) endometrial cancers and nine of 22 (41 percent) ovarian cancers. The endometrial cancers may have been easier to find because cells from those tumors do not have as far to travel as ovarian cancer cells. The Hopkins researchers will study whether inserting the Pap brush deeper, testing during different times of the menstrual cycle, or other factors might improve detection of ovarian cancer.

The investigators note that larger-scale studies are needed prior to clinical use on women, but they believe the test has the potential to pioneer genomic-based, cancer screening tests. [Emphasis added]

The Papanicolaou (Pap) test, during which cells collected from the cervix are examined for microscopic signs of cancer, is widely and successfully used to screen for cervical cancers. Today, many women’s Paps undergo an additional DNA-based test to see if they harbor the human papillomavirus (HPV), which can spur cervical cancer. However, no routine screening method is available for ovarian or endometrial cancers.

Luis Alberto Diaz, M.D.

Since the Pap test occasionally contains cells shed from the ovaries or endometrium, cancer cells arising from these organs could be present in the fluid as well, says Luis Diaz, M.D., associate professor of oncology at Johns Hopkins, as well as director of translational medicine at the Ludwig Center for Cancer Genetics and Therapeutics and director of the Swim Across America Laboratory, also at Johns Hopkins. The laboratory is sponsored by a volunteer organization that raises funds for cancer research through swim events. “Our genomic sequencing approach may offer the potential to detect these cancer cells in a scalable and cost-effective way,” adds Diaz.

Hear Dr. Diaz discuss the PapGene test research in this hyperlinked podcast, courtesy of the American Association for the Advancement of Science.

Cervical fluid of patients with gynecologic cancer carries normal cellular DNA mixed together with DNA from cancer cells, according to the investigators. The investigators’ task was to use genomic sequencing to distinguish cancerous from normal DNA.

The scientists had to determine the most common genetic changes in ovarian and endometrial cancers in order to prioritize which genomic regions to include in their test. They searched publicly available genome-wide studies of ovarian cancer, including those done by other Johns Hopkins investigators, to find mutations specific to ovarian cancer. Such genome-wide studies were not available for the most common type of endometrial cancer, so they conducted genome-wide sequencing studies on 22 of these endometrial cancers.

From the ovarian and endometrial cancer genome data, the Johns Hopkins-led team identified 12 of the most frequently mutated genes in both cancers and developed the PapGene test with this insight in mind.

The investigators then applied PapGene on Pap test samples from ovarian and endometrial cancer patients at The Johns Hopkins Hospital, Memorial Sloan-Kettering Cancer Center, the University of São Paulo in Brazil and ILSbio, a tissue bank. The new test detected both early- and late-stage disease in the endometrial and ovarian cancers tested. No healthy women in the control group were misclassified as having cancer.

Animation of PapGene:

Looking ahead, the investigators’ next steps include applying PapGene on more samples and working to increase the test’s sensitivity in detecting ovarian cancer. “Performing the test at different times during the menstrual cycle, inserting the cervical brush deeper into the cervical canal, and assessing more regions of the genome may boost the sensitivity,” says Chetan Bettegowda, M.D., Ph.D., assistant professor of neurosurgery at Johns Hopkins and a member of the Ludwig Center as well.

Together, ovarian and endometrial cancers are diagnosed in nearly 70,000 women in the United States each year, and about one-third of them will die from it. “Genomic-based tests could help detect ovarian and endometrial cancers early enough to cure more of them,” says graduate student Yuxuan Wang, who notes that the cost of the test could be similar to current cervical fluid HPV testing, which is less than $100.

PapGene is a high-sensitivity approach for the detection of cancer-specific DNA mutations, according to the investigators; however, false mutations can be erroneously created during the many steps — including amplification, sequencing and analysis — required to prepare the DNA collected from a Pap test specimen for sequencing. This required the investigators to build a safeguard into PapGene’s sequencing method, designed to weed out artifacts that could lead to misleading test results.

“If unaccounted for, artifacts could lead to a false positive test result and incorrectly indicate that a healthy person has cancer,” says graduate student Isaac Kinde.

Kinde added a unique genetic barcode — a random set of 14 DNA base pairs — to each DNA fragment at an initial stage of the sample preparation process. Although each DNA fragment is copied many times before eventually being sequenced, all of the newly copied DNA can be traced back to one original DNA molecule through their genetic barcodes. If the copies originating from the same DNA molecule do not all contain the same mutation, then an artifact is suspected and the mutation is disregarded. However, bonafide mutations, which exist in the sample before the initial barcoding step, will be present in all of the copies originating from the original DNA molecule.

The Johns Hopkins test results demonstrate that DNA from most endometrial and a fraction of ovarian cancers can be detected in a standard liquid-based Pap smear specimen obtained during routine pelvic examination. Although improvements need to be made before applying this test in a routine clinical manner, it represents a promising first step toward a broadly applicable screening methodology for the early detection of gynecologic malignancies.

“This is very encouraging, and it shows great potential,” said American Cancer Society genetics expert Michael Melner.

“We are a long way from being able to see any impact on our patients,” cautioned Dr. Shannon N. Westin of the University of Texas MD Anderson Cancer Center. Dr. Westin reviewed the research in an accompanying editorial, and said the ovarian cancer detection would need improvement if the test is to work. But Dr. Westin noted that ovarian cancer has poor survival rates because it’s rarely caught early. “If this screening test could identify ovarian cancer at an early stage, there would be a profound impact on patient outcomes and mortality,” Westin said.

More than 22,000 U.S. women are diagnosed with ovarian cancer each year, and more than 15,000 die. Symptoms such as bloating and pelvic or abdominal pain are seldom obvious until the cancer is more advanced, and numerous attempts at screening tests have failed.

Endometrial cancer affects about 47,000 U.S. women a year, and kills about 8,000. There is no screening test for it either, but most women are diagnosed early because of postmenopausal bleeding.

___________________________

Funding for the research was provided by Swim Across America, the Commonwealth Fund, the Hilton-Ludwig Cancer Prevention Initiative, the Virginia & D.K. Ludwig Fund for Cancer Research, the Experimental Therapeutics Center of the Memorial Sloan-Kettering Cancer Center, the Chia Family Foundation, The Honorable Tina Brozman Foundation, the United Negro College Fund/Merck Graduate Science Research Dissertation Fellowship, the Burroughs Wellcome Career Award for Medical Scientists, the National Colorectal Cancer Research Alliance and the National Institutes of Health’s National Cancer Institute (N01-CN-43309, CA129825, CA43460).

In addition to Kinde, Bettegowda, Wang and Diaz, investigators participating in the research include Jian Wu, Nishant Agrawal, Ie-Ming Shih, Robert Kurman, Robert Giuntoli, Richard Roden and James R. Eshleman from Johns Hopkins; Nickolas Papadopoulos, Kenneth Kinzler and Bert Vogelstein from the Ludwig Center at Johns Hopkins; Fanny Dao and Douglas A. Levine from Memorial Sloan-Kettering Cancer Center; and Jesus Paula Carvalho and Suely Kazue Nagahashi Marie from the University of São Paulo.

Papadopoulos, Kinzler, Vogelstein and Diaz are co-founders of Inostics and Personal Genome Diagnostics. They own stocks in the companies and are members of their Scientific Advisory Boards. Inostics and Personal Genome Diagnostics have licensed several patent applications from Johns Hopkins. These relationships are subject to certain restrictions under The Johns Hopkins University policy, and the terms of these arrangements are managed by the university in accordance with its conflict-of-interest policies.

____________________________

Citations:

I. Kinde, C. Bettegowda, Y. Wang, J. et. al. Evaluation of DNA from the Papanicolaou Test to Detect Ovarian and Endometrial Cancers. Sci. Transl. Med. 5, 167ra4 (2013).

S. N. Westin, G. B. Mills, A. P. Myers, Repurposing the Pap Smear: One Step Closer to Gynecologic Cancer Screening. Sci. Transl. Med. 5, 167ps1 (2013).

Additional Sources:

Johns Hopkins Scients Use Pap Test Fluid to Detect Ovarian, Endometrial Cancers, John Hopkins Medicine, Press Release, January 9, 2013.

Retooling Pap Test To Spot More Kinds Of Cancer, The Associated Press via National Public Radio, January 9, 2013.

“Whither Thou Goest, I Will Go …”

Today, we celebrate the life of Elizabeth (“Libby”) Remick on the fourth anniversary of her passing — July 28, 2008.

Elizabeth Kay Remick (1982 – 2008)

Today, we celebrate the life of Elizabeth (“Libby”) Remick on the fourth anniversary of her passing — July 28, 2008. Libby was only 26 years old when she died from ovarian clear cell cancer. The Libby’s H*O*P*E* website is dedicated to Elizabeth’s memory.

Some people come into our lives and quickly go.
Some people stay for awhile,
and move our souls to dance.
They awaken us to a new understanding,
leave footprints on our hearts,
and we are never, ever the same.
— Flavia Weedn

As many of you know, we consider Libby the driving force and inspiration behind our ongoing support work for ovarian cancer survivors and their families. Libby’s spirit inspires us on a daily basis. We believe that Libby’s eternal love and support of ovarian cancer survivors and their families are limitless; this is especially true when the situation is labeled “hopeless.” We were reminded of this fact earlier this week after coming across a touching story dating back to 1940, which epitomizes the close and unbreakable bond between the U.S. and Great Britain — quite apropos given the opening of the 2012 Summer Olympics in London yesterday.

Between September 7, 1940 and May 16, 1941, the German Luftwaffe (air force) engaged in a bombing campaign designed to demoralize the British people into surrender while destroying the country’s economic war production. At one point, London (and 16 other British cities) were bombed on 57 consecutive nights during the German air campaign. As a result of the German raids, more than 40,000 civilians (almost half of them in London) were killed, and more than one million London homes were destroyed or damaged.  The history books simply refer to this desperate and seemingly hopeless time period in England as “the Blitz” (derived from the German word “blitzkrieg,” meaning “lighting war”).

During this extremely difficult time period, Winston Churchill, England’s Prime Minister, knew that he had to rouse the British people to resist Adolf Hitler’s armed forces. Churchill also understood that England alone could not defeat Germany, and he recognized early on that the assistance of the U.S. would be necessary for ultimate victory. Churchill eagerly sought out U.S. assistance, and ultimately, American participation in support of England’s war effort.

The actions taken by Churchill to encourage U.S. assistance included welcoming the emissaries that were sent by President Franklin D. Roosevelt; foremost among them was Harry L. Hopkins. As Roosevelt’s closest wartime aide, Harry Hopkins played a crucial role in nurturing the Anglo-American partnership. At the direction of President Roosevelt, Harry Hopkins journeyed to England in the midst of the Blitz, and he later convinced the U.S. President that Churchill and the British people would fight on to the end, and therefore, must be supported at any cost.  During Hopkins’ visit, he spoke directly to Churchill about America’s strong support of England, regardless of the circumstances.

In January 1941, at the end of his visit with Churchill, Harry Hopkins summarized American support, as part of a dinner toast, by referencing the unbreakable bond of loyalty cited in the Book of Ruth 1:16, which begins with Ruth’s plea to a close family relative during difficult times: ” Intreat me not to leave thee, or to return from following after thee …”  In his toast, and with a deeply emotional tone, Hopkins simply recited the remainder of that biblical verse:

“‘Whither thou goest, I will go; and where thou lodgest, I will lodge: thy people shall be my people, and thy God my God’ — even to the end.”

According to those present at the dinner, Hopkins’ vow of American loyalty reduced the English Prime Minister to tears. Winston Churchill knew exactly what Hopkins meant, and he later stated: “Harry Hopkins’ impromptu sermon seemed like a rope thrown to a drowning man.” In the end, Hitler’s Blitz did not achieve its intended goal of demoralizing the British people into surrender; rather, it caused them to unite among themselves and forge an unbreakable bond with the U.S., which led to ultimate victory.

We know that if Libby were alive today, she would extend the same loyalty, perseverance, hope, and support towards ovarian cancer survivors and their families, similar to that cited in The Book of Ruth 1:16.  Libby’s H*O*P*E* represents the physical manifestation of Libby’s spirit, including the steadfast support of all ovarian cancer survivors and their families during difficult times.

Although Libby is no longer physically present among us, a traditional Native American Prayer reminds us that she remains forever present in our lives:

I give you this one thought to keep -
I am with you still – I do not sleep.
I am a thousand winds that blow,
I am the diamond glints on snow,
I am the sunlight on ripened grain,
I am the gentle autumn rain.
When you awaken in the morning’s hush,
I am the sweet uplifting rush,
of quiet birds in circled flight.
I am the soft stars that shine at night.
Do not think of me as gone -
I am with you still in each new dawn.

– Traditional Native American Prayer

Libby, we love you, miss you, and will never forget you. We do not think of you “as gone,” and we know that you are with us “in each new dawn.” Thank you for your life and eternal inspiration.

___________________

Related Libby’s H*O*P*E*™ Postings:

• The Mirror: “What is the Meaning of Life?”, by Paul Cacciatore, July 28, 2011.

• “Smile, Open Your Eyes, Love and Go On.,” by Paul Cacciatore, July 28, 2010.

• Vox Populi*: Libby, We’ll Be Missing You, by Paul Cacciatore, July 28, 2009.

• A Requiem Hallelujah, But Don’t Let There Be a Hole in the World Tomorrow, by Paul Cacciatore, July 28, 2008.

Proposed Federal Gov’t Rule Adds Ovarian Cancer to 9/11 World Trade Center Health Program List of Covered Conditions

On June 13, 2012, the federal government will publish a proposed rule that will add ovarian cancer to the list of conditions covered by the World Trade Center Health Program. It is anticipated that the proposed rule will take several months to finalize prior to becoming effective. The WTC Health Program was established by the James Zadroga 9/11 Health and Compensation Act of 2010, which provides health benefits and financial compensation to those harmed by the attacks of September 11th and its aftermath.

The World Trade Center Health Program (WTC Health Program) was established by the James Zadroga 9/11 Health and Compensation Act of 2010, which provides health benefits and financial compensation to those harmed by the attacks of September 11th and its aftermath.

The WTC Health Program provides services to responders, workers, and volunteers who helped with rescue, recovery, and cleanup at the World Trade Center and related sites located within the defined “New York City disaster area.” It also provides services for survivors who lived, worked, or were attending school in the area. The WTC Health Program will also be serving responders to the 9/11 attacks at the Pentagon in Arlington, Virginia, and the Flight 93 crash site in Shanksville, Pennsylvania

The WTC Health Program is administered by the National Institute for Occupational Safety and Health (NIOSH). After conducting a long-term study, NIOSH stated in a recent administrative filing that it favored a major expansion of the existing $4.3 billion WTC Health Program to include eligible individuals with 50 types of cancer, covering 14 broad categories of the disease. The specifics underlying NIOSH’s administrative decision will be published on June 13, 2012 in the Federal Register as a Notice of Proposed Rulemaking, entitled World Trade Center Health Program; Addition of Certain Types of Cancer to List of WTC-Related Health Conditions. Within the proposed rule, ovarian cancer (i.e., “malignant neoplasms of the ovary”) is listed as one of the enumerated cancer types.

Pursuant to NIOSH’s proposed rule, the WTC Health Program will provide medical testing and care for specific symptoms and illnesses related to being exposed to the disaster sites. The services will be provided by clinics and hospitals that have expertise in the diagnosis and treatment of 9/11-related health conditions.

It is important to note that NIOSH’s proposed rule does not represent a final administrative determination. The Notice of Proposed Rulemaking is subject to public review and a 30-day comment period. Once public comment is received, NIOSH will consider and address those comments as appropriate before issuing a final ruling. The proposed rule may change prior to finalization, or it may not be finalized at all.

If NIOSH determines that it is appropriate to issue a final rule to cover select cancer types, and a final rule is published, additional steps would be necessary before an eligible responder or survivor could receive care and treatment under the WTC Health Program. The physician diagnosing the cancer would be responsible for reviewing the individual’s exposure history to determine whether her cancer could be related to a 9/11 exposure; the individual’s diagnosis must then be certified by NIOSH before care and treatment can begin.

Sources:

• Statement from WTC Program Administrator John Howard, M.D., The National Institute for Occupational Safety and Health, Centers for Disease Control & Prevention, U.S. Department of Health & Human Services, June 8, 2012.

• World Trade Center Health Program.

• World Trade Center Health Program; Addition of Certain Types of Cancer to List of WTC-Related Health Conditions, Federal Register Notice of Proposed Rulemaking, June 13, 2012. (Pre-publication PDF copy)

Preclinical Testing Suggests That Apoptosis Protein Inhibitor AT-406 Is Effective Against Ovarian Cancer; Initial Phase I Solid Tumor Clinical Trial Ongoing

In preclinical testing, Mount Sinai School of Medicine researchers demonstrated the anti-ovarian cancer effectiveness of AT-406, an inhibitor of apoptosis proteins, as a single agent and in the combination with carboplatin.  As of this writing, Ascenta Therapeutics is conducting an open and ongoing phase I clinical study in patients with advanced solid tumors and lymphomas.

Apoptosis Proteins: A Promising Target For Cancer Therapeutics?

Apoptosis increasing from normal cells (top) to apoptotic ones (bottom). (Photo: Wikipedia)

Human cells are programmed to survive, die or proliferate through a complex system of regulatory controls.  Apoptosis — also know as “programmed cell death” — is a precisely regulated, complex process through which normal cells in the body die after a given life span, ensuring that defective, damaged, or redundant cells are eliminated.

The human body use apoptosis, or programmed cell death, to eliminate abnormal or unwanted cells. As a result of accumulated genomic alterations, it seems that cancer cells often fail to execute an apoptotic program, which allows them to live indefinitely and grow uncontrollably. The breakdown of the cellular apoptosis regulatory machinery is sometimes a dominant characteristic of cancer. Many current cancer therapies, including chemotherapeutic agents, radiation, and immunotherapy, work by inducing apoptosis in cancer cells. However, because the normal apoptotic biological pathways are sometimes defective, many cancer cells are inherently resistant or develop resistance to various therapies.  An emerging direction for drug development involves the direct targeting of apoptotic proteins to induce cell death and/or reduce treatment resistance.

AT-406 — A New Inhibitor of Apoptosis Proteins — is Effective in Preclinical Testing Against Ovarian Cancer.

(Photo: University of Michigan Heath System)

AT-406 is a novel and orally-active small molecule drug designed to promote programmed cell death (apoptosis) in tumor cells by blocking the activity of inhibitors of apoptosis proteins (IAPs), including XIAP, c-IAP1, c-IAP2, and ML-IAP, to create conditions in which apoptosis can proceed.  Based on this designed activity, AT-406 is best described as a multi-IAP inhibitor. IAPs are key components of the complex cascade of protein signaling that activates enzymes (called “caspases“) to initiate the breakdown of the cancer cell. AT-406 is thought to mimic the activity of Smac (second mitochondria-derived activator of caspases) by binding to XIAP and preventing it from inhibiting caspase activation. Upon binding to cIAP1 and cIAP2, AT-406 induces rapid degradation of these proteins and promotes apoptosis through activation of the death-receptor complex and caspase 8.

Ascenta Therapeutics (Ascenta), the developer of AT-406, reported that the drug has already demonstrated single-agent antitumor activity in multiple preclinical xenograft models of human cancer, including breast cancer, pancreatic cancer, prostate cancer, and lung cancer. Ascenta also noted that AT-406 has also been shown to work synergistically with conventional chemotherapeutic and targeted agents (such as TRAIL and tyrosine kinase inhibitors) in preclinical tumor models.

Mount Sinai School of Medicine researchers evaluated AT-406 in ovarian cancer cells as a single agent, and in the combination with carboplatin, for therapeutic effectiveness and mechanism of action. The researchers reported that AT-406 had significant single agent activity in 60% of the human ovarian cancer cell lines examined in vitro, and inhibited ovarian cancer progression in vivo. Notably, three of the five carboplatin-resistant cell lines tested sensitive to AT-406, thereby highlighting the therapeutic potential of AT-406 for patients with inherent or acquired platinum drug resistance.

Additionally, the researchers also determined that AT-406 enhanced carboplatin-induced ovarian cancer cell death and increased the survival of the experimental in vivo test mice. This result suggests a synergy created by this two drug  combination, whereby AT-406 sensitizes the response of these cancer cells to carboplatin. From a mechanism of action perspective, the researchers demonstrated that AT-406 induced apoptosis correlated with the drug’s ability to down-regulate XIAP,  whereby AT-406 induces cIAP1 degradation in both AT-406 sensitive and resistant cell lines. Collectively, these results demonstrate, for the first time, the anti-ovarian cancer efficacy of AT-406 as a single agent and in the combination with carboplatin. The researchers believe that AT-406 may represent a novel therapy for ovarian cancer patients, especially for patients exhibiting resistance to the platinum-based therapies.

Initial Phase I Clinical Study of AT-406 in Patients With Advanced Solid Tumors & Lymphomas

Ascenta is currently conducting clinical trials of AT-406 within the U.S. in patients with a variety of solid tumors and lymphomas. As of this writing, Ascenta is conducting a phase I, dose-escalation, open-label, multi-center study (University of Michigan Comprehensive Cancer Center, Mayo Clinic, and Duke University Medical Center) in patients with advanced solid tumors and lymphomas to evaluate the safety, tolerability and pharmacology of AT-406 when administered orally. The ClinicalTrials.gov Identifier Number for this trial is NCT01078649.

It is important to note that phase I trials usually enroll a small numbers of patients who have advanced cancer that cannot be treated effectively with standard treatments, or for which no standard treatment exists. Although evaluating the effectiveness of a drug is the primary goal of a phase II (not phase I) clinical study, medical investigators do look for evidence that the study treatment might be useful in a phase I clinical study.

Sources:

• Brunckhorst MK, et al. AT-406, an orally active antagonist of multiple inhibitor of apoptosis proteins, inhibits progression of human ovarian cancer. Cancer Biol Ther. 2012 Jul 1;13(9). [Epub ahead of print] PMID: 22669575.

• AT-406 Clinical Trial Protocol Summary: A Phase I, Open Label, Multi-Center, Dose Escalation Study of the Safety, Tolerability, Pharmacodynamic and Pharmacokinetic Properties of Orally Administered AT-406 in Patients With Advanced Solid Tumors and Lymphomas; ClinicalTrials.gov Identifier: NCT01078649.

U.S. Food & Drug Administration Acts to Bolster Supply of Critically Needed Cancer Drugs Including Doxil

The U.S. Food and Drug Administration today announced a series of steps to (i) increase the supply of critically needed cancer drugs, and (ii) build upon President Obama’s Executive Order to help prevent future drug shortages.  To alleviate the Doxil cancer drug shortage, the FDA approved  the temporary importation of a replacement drug named “Lipodox” (doxorubicin hydrochloride liposome injection), with the expectation of  ending the U.S. shortage and fully meeting patient needs in the coming weeks. Doxil is an important weapon in the fight against recurrent ovarian cancer.

The U.S. Food and Drug Administration today announced a series of steps designed to increase the supply of critically needed cancer drugs, and build upon President Obama’s Executive Order, dated October 31, 2011 (No. 13588), in an attempt to prevent future drug shortages.

Margaret Hamburg, M.D., Commissioner, U.S. Food & Drug Administration

“A drug shortage can be a frightening prospect for patients and President Obama made it clear that preventing these shortages from happening is a top priority of his administration,” said FDA Commissioner Margaret A. Hamburg, M.D. “Through the collaborative work of the FDA, industry, and other stakeholders, patients and families waiting for these products or anxious about their availability should now be able to get the medication they need.”

In response to the critical shortage of the cancer drug Doxil (doxorubicin hydrochloride liposome injection) and rapidly declining supplies of methotrexate, the FDA took proactive steps needed to increase available supply for patients in the U.S.

For Doxil, there will be temporary importation of a replacement drug named “LipoDox” (doxorubicin hydrochloride liposome injection), which is expected to end the shortage and fully meet patient needs in the coming weeks.

For methotrexate, in addition to already announced actions, the FDA approved a new manufacturer of preservative-free formulation of methotrexate that is expected to further bolster supply and help avert a shortage of this lifesaving medicine. the FDA expedited review of the application to help address this potential shortage.

In response to President Obama’s Executive Order #13588 regarding prescription drug shortages, the FDA today issued draft guidance to industry which provides detailed requirements for both mandatory and voluntary notifications to the FDA of issues that could result in a drug shortage or supply disruption. Because of President Obama’s Executive Order #13588 and the FDA’s letter to manufacturers on the same day, increased awareness of the importance of early notification has resulted in a sixfold increase in voluntary notifications by industry of potential shortages. In 2011, there were a total of 195 drug shortages prevented. Since the issuance of Presidential Executive Order #13588, the FDA has prevented 114 drug shortages.

Under the FDA’s exercise of enforcement discretion, the chemotherapeutic drug LipoDox will be imported as an alternative to Doxil. Doxil is used in multiple treatment regimens, including treatment of ovarian cancer after failure of platinum-based chemotherapy (e.g., carboplatin or cisplatin). The drug is also indicated for use in AIDS-related Kaposi’s sarcoma and multiple myeloma. The FDA anticipates that the incoming supply of LipoDox will be able to fully meet patient needs.

The FDA’s exercise of enforcement discretion for Lipodox is a temporary, limited arrangement specific to Sun Pharma Global FZE (a United Arab Emirates entity) and its authorized distributor, Caraco Pharmaceutical Laboratories Ltd. (a U.S. subsidiary of Sun Pharmaceutical Industries Ltd., a leading Indian pharmaceutical company).

Temporary importation of unapproved foreign drugs is considered in rare cases when there is a shortage of an approved drug that is critical to patients and the shortage cannot be resolved in a timely fashion with FDA-approved drugs.

When a company is identified that is willing and able to import the needed drug product, the FDA evaluates the foreign-approved drug to ensure that it is of adequate quality and that the drug does not pose significant risks for U.S. patients. Only after successful evaluation of these factors does the FDA exercise its enforcement discretion for the temporary importation of an overseas drug into the U.S. market.

Methotrexate is a drug that is needed for the treatment of many forms of cancer and other serious diseases. For example, preservative-free methotrexate is needed for the intrathecal (injection into the fluid surrounding the brain and spinal cord) treatment of children with acute lymphocytic leukemia (ALL), as well as high-dose therapy of osteosarcoma.

To alleviate the shortage of methotrexate, the FDA has successfully engaged several firms to assist in maintaining supplies to meet all patient needs. First, the FDA has prioritized the review and approval of a preservative-free methotrexate generic drug manufactured by APP Pharmaceuticals (APP) and expects that product to become available in March 2012 and continue indefinitely. Second, Hospira expedited release of additional methotrexate supplies, resulting in 31,000 vials of new product – enough for more than one month’s worth of demand – being shipped to hundreds of U.S. hospitals and treatment centers today. The FDA is actively working with other manufacturers of methotrexate who have also stepped up to increase drug production for the purpose of meeting patient needs, including Mylan and Sandoz Pharmaceuticals.

APP’s application for preservative-free methotrexate is a supplement to its already approved generic drug application that the firm had previously discontinued. When the FDA became aware of potential problems with the supply of the drug (attributable to the voluntary plant closing of the largest methotrexate manufacturer, Ben Venue Laboratories), the agency reached out to other firms to see how the FDA could assist to meet the shortfall.

Prior to the approval of APP’s application, and the subsequent Ben Venue Laboratories’ voluntary shutdown, the FDA worked with Ben Venue on release of already manufactured preservative-free methotrexate, following its confirmation of the safety of remaining drug inventory. This supply is available already and will provide emergency supplies as the other firms also work to increase production of methotrexate in response to requests by the FDA and the public.

On October 31, 2011, the Obama Administration also announced its support for bipartisan legislation that would (i) require all prescription drug shortages to be reported to the FDA, and (ii) give the FDA new authority to enforce these requirements. While additional manufacturing capacity is necessary to fully address the drug shortage problem, additional early notification to the FDA can have a significant, positive impact on addressing the incidence and duration of drug shortages.

For more FDA information relating to the U.S. drug shortage, please click on the topics listed below:

Drug Shortages

Drug Shortage Guidance (“Guidance for Industry — Notification to FDA of Issues that May Result in a Prescription Drug or Biological Product Shortage – Draft Guidance,” dated February 2012)

Labeling for Doxil (doxorubicin hydrochloride liposome injection)

Letter from Sun Pharma Global FZE to healthcare professionals regarding doxorubicin, dated January 27, 2012.

FDA letter to Industry regarding drug shortage, dated October 31, 2011.

Labeling for methotrexate

Consumer Inquiries: 888-INFO-FDA

About the U.S. Food & Drug Administration (FDA)

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The FDA is also responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Source: FDA acts to bolster supply of critically needed cancer drugs, FDA News Release, U.S. Food & Drug Administration, February 21, 2012.

Can Iran Solve the Current U.S. Doxil/Caelyx Cancer Drug Shortage?

Iran expects to bring a  cancer nanodrug called “Sinadoxosome” to market next month. Sinadoxosome is apparently similiar to pegylated liposomal doxorubicin which is marketed under the brand name “Doxil” in the U.S. and “Caelyx” in Europe. Doxil/Caelyx has been in extreme short supply in the U.S. and Europe, thereby causing potential detriment to many ovarian cancer patients.

Iran inaugurated the production line of an anti-cancer nanodrug under the name “Sinadoxosome” in the Northern city of Rasht, and the medicine will soon come to market.

In addition to producing the amount of nanodrug required by Iran, the new drug production line makes possible the exportation of the drug to other countries. The drug acquired the necessary certificates from Nanotechnology Committee of the Ministry of Health, Treatment, and Medical Education in November 2011.

Dr. Mahmoud Reza Ja’fari, the Managing Director of Exir Nano Sina Company, told the Iran Nanotechnology Initiative Council’s reporter that the anti-cancer drug Sinadoxosome would be presented to the market next month.

“This product has been produced by the knowledge-based company Exir Nano Sina in association with Iran Nanotechnology Initiative Council. It has acquired the production certificate from the Ministry of Health, Treatment, and Medical Education,” Dr. Ja’fari added.

Pointing to the fact that the production of this medicine had been “monopolized” by European countries (under the “Caelyx” brand name) and by the United States (under the “Doxil” brand name), the Head of Nanotechnology Research Centre of Mashhad University of Medical Sciences said: “The importation of this medicine cost [sic] $5 mln annually. However, this medicine will be presented to the patients at one-third of the price of the foreign drug after the establishment of Sinadoxosome production line.”

Sinadoxosome contains nano liposomes that contain doxorubicin anti-cancer medicine. It targets the tumor tissue and boosts the effect of the medicine but decreases its side effects. The medicine has applications in the treatment of ovarian cancer, breast cancer, leukemia, and Kaposi’s sarcoma (a type of soft tissue cancer).

The production line involving the Sinadoxosome anti-cancer drug was established on February 8, 2012, in the presence of Iran Nanotechnology Initiative Council’s authorities and the managing director and researchers of the Sobhan Oncology Pharmaceutical Company.

*          *          *

In the YouTube video presented below, U.S. Senator Orrin Hatch (R-Utah), Ranking Member of the Senate Finance Committee, delivered the opening statement at a 2011 committee hearing examining the impact of drug shortages in America.

Source: Iran to Present New Anti-Cancer Nanodrug to Market Soon, Iran Nano-Technology Initiative Council, February 15, 2012.

Additional Doxil & Drug Shortage Information:

• Important Updates on DOXIL® Supply Shortage, Doxil.com

• Drug Shortages, U.S. Food & Drug Administration, http://www.fda.gov.

• What’s Behind Our National Drug Shortages?, by Glenn Braunstein, M.D., The Huffington Post, February 6, 2012.

• Shortage of prescription drugs, by Tracy Connor, New York Daily News, January 21, 2012.

• Gatesman ML, Smith, TJ, The Shortage of Essential Chemotherapy Drugs in the United States; N Engl J Med 2011; 365:1653-1655.

Small Study Finds Tumor-Freezing Cryoablation Treatment Extends Survival of Select Metastatic Ovarian Cancer Patients

A small study of 21 ovarian cancer patients reported that killing tumors by freezing them through cryoablation can extend the lives of select women with metastatic disease which has spread to the abdomen, liver, lung or bone, and can not be removed surgically. From the time of diagnosis of metastatic disease, the average patient survival time was more than four years and seven months.

"Cryoablation" is a minimally invasive treatment that uses extreme cold ("cyro") to freeze and destroy diseased tissue ("ablation"), including cancer cells. (Photo: Wikipedia)

Killing tumors by freezing them through cryoablation can extend the lives of women with ovarian cancer that has spread to other parts of the body and is cost-effective, according to research being presented at the 4th annual Symposium on Clinical Interventional Oncology (CIO), in collaboration with the International Symposium on Endovascular Therapy (ISET).

Cryoablation Study Results

The study included 21 patients whose tumors in the abdomen, liver, lung and bone could not be removed surgically. Cryoablation was used to treat 48 tumors, killing 47 of them (98 percent). From the time of diagnosis of metastatic disease, average patient survival time was more than four years and seven months. That’s significant because when tumors are not successfully removed surgically – which occurs in about 60 percent of cases, according to studies – women typically survive from about seven months to 2 ½ years. On average, more than three years had transpired from the time of diagnosis to the first cryoablation treatment, meaning these women had already passed their expected survival time, and yet cryoablation was able to extend their survival even further. Some patients had multiple cryoablation treatments and of 41 procedures, there were three major complications (7 percent). The complications included two deaths that were attributed to the cancer, not to the procedure.

The study also determined the treatment was extremely cost-effective, costing an average of $26,806 per life year saved, well below the current standard of $100,000.

Hyun J. Bang, M.D., Radiologist Resident, Wayne State University/Detroit Medical Center

“This study adds to the evidence that cryoablation is an effective option for patients who can’t have surgery,” said study author Hyun J. Bang, M.D., a radiologist resident at Wayne State University/Detroit Medical Center. “This procedure is often overlooked, but based on the high survival rate, cost effectiveness, consistent local control and safety of the procedure, we should be taking a closer look at cryoablation.”

In cryoablation, a small needle is inserted into the tumor using imaging guidance. High pressure argon flows to the tip of the cryoprobe where it expands in an internal chamber, causing a powerful cooling effect on the outside of the probe. This allows for rapid ice formation which freezes and kills tumor cells.

For more about CIO and ISET, visit www.ISET.org/oncology.

Cryoablation Study Shortcomings — Potential Selection Bias

“While an interesting abstract, it must be stressed that the total number of patients included is extremely limited, and it is not appropriate to make any statement regarding the impact of this strategy on survival,” cautioned Maurie Markman, M.D., the senior vice president of clinical affairs and national director of medical oncology at the Cancer Treatment Centers of America Eastern Regional Medical Center in Philadelphia, Pennsylvania, in an interview with Medscape Medical News.

“Any observed outcome could very easily reflect bias in the selection of patients who have been included in this series. Considerable additional clinical evaluation must be undertaken to include far larger patient populations before any statement can be made regarding the potential of this approach to be a reasonable alternative to the current standard of care in the management of ovarian cancer,” Dr. Markman added.

Sources:

• Tumor-Freezing Treatment Gives Ovarian Cancer Patients Extra Time, ISET Daily News (page 4 digital edition), The International Symposium on Endovascular Therapy, Sunday, January 15, 2012.

• Targeted Cryoablation Boosts Survival in Ovarian Cancer, by Martha Kerr, Medscape Medical News, January 19, 2012. [Free Medscape registration required to view article]

Canadian Researchers Link DICER1 Gene Mutation to Non-Epithelial Ovarian Cancers & Other Rare Tumor Types

Canadian researchers affiliated with the Ovarian Cancer Research Program of British Columbia report that recurrent, lifetime-acquired mutations affecting the DICER1 gene occur in a range of nonepithelial ovarian tumors as well as other rare cancer tumor types, and appear common in Sertoli-Leydig ovarian tumors. The study findings were published online today in the New England Journal of Medicine.

Dr. Gregg Morin, Head of Proteomics, Michael Smith Genome Sciences Centre, BC Cancer Agency; DICER 1 Mutation Ovarian Cancer Study Co-Leader

Dr. David Huntsman, Genetic Pathologist & Director of the Ovarian Cancer Research Program of British Columbia at the BC Cancer Agency & Vancouver Coastal Health Research Institute; DICER 1 Mutation Ovarian Cancer Study Co-Leader

Scientists at the British Columbia (BC) Cancer Agency, Vancouver Coastal Health Research Institute, and the University of British Columbia (UBC) are excited over a discovery made while studying rare tumor types.

Dr. David Huntsman, genetic pathologist and director of the Ovarian Cancer Program of BC (OvCaRe) at the BC Cancer Agency and Vancouver Coastal Health Research Institute, and Dr. Gregg Morin, a lead scientist from the Michael Smith Genome Sciences Centre at the BC Cancer Agency, led a research team who discovered that mutations in rare, seemingly unrelated cancers were all linked to the same gene, known as “DICER1.” The study findings were published online today in the New England Journal of Medicine. [1]

Background: RNA Interference, MicroRNAs, and DICER.

Nucleic acids are molecules that carry genetic information and include DNA (deoxyribonucleic acid) and RNA (ribonucleic acid). The DNA segments that carry genetic information are called “genes.” Together these molecules form the building blocks of life. DNA contains the genetic code or “blueprint” used in the development and functioning of all living organisms, while “messenger RNAs” or mRNAs help to translate that genetic code into proteins by acting as a messenger between the DNA instructions located in the cell nucleus and the protein synthesis which takes place in the cell cytoplasm (i.e., outside the cell nucleus, but inside the outer cell membrane). Accordingly, DNA is first “transcribed” or copied into mRNA, which, in turn, gets “translated” or synthesized into protein.

“RNA interference” (RNAi) is a mechanism through which gene expression is inhibited at the translation stage, thereby disrupting the protein production within a cell. RNAi is considered one of the most important discoveries in the field of molecular biology. Andrew Fire, Ph.D., and Craig C. Mello, Ph.D. shared the 2006 Nobel Prize in Physiology or Medicine for work that led to the discovery of the RNAi mechanism. While the mechanism itself is termed “RNA interference,” there are two major types of RNA molecules that play a key role in effectuating that interference. The first type of RNA molecules consists of “microRNAs” or miRNAs, while the second type consists of “small interfering RNAs” or siRNAs.

Current thinking suggests that RNAi evolved as a cellular defense mechanism against invaders such as RNA viruses. When they replicate, RNA viruses temporarily exist in a double-stranded form. This double-stranded intermediate would trigger RNAi and inactivate the virus’ genes, thereby preventing viral infection. RNAi may also have evolved to combat the spread of genetic elements called “transposons” within a cell’s DNA. Transposons can wreak havoc by jumping from spot to spot on a genome, sometimes causing mutations that can lead to cancer or other diseases. Like RNA viruses, transposons can take on a double-stranded RNA form that would trigger RNAi to clamp down on the potentially harmful “jumping gene” activity. Also, as noted above, RNAi is important for regulating gene expression. For example, the turning down of specific genes is critical to proper embryonic development.

Of relevance to the Canadian study findings within the context of RNAi are miRNAs. MiRNAs can bind to mRNAs and either increase or decrease their activity, for example, by preventing a mRNA from producing a protein. [2] In this context, “gene silencing” can occur through mRNA degradation or prevention of mRNA translation.  MiRNAs play an integral role in numerous biological processes, including the immune response, cell-cycle control, metabolism, viral replication, stem cell differentiation and human development. MiRNA expression or function is significantly altered in many disease states, including cancer.

Because of its involvement in miRNA processing, the DICER1 gene plays an important role in maintaining health. It carries out a “factory style” function which involves chopping up miRNAs to activate them. [Ref. 2] These miRNAs, in turn, control hundreds of other genes as noted above. Based upon a study led by investigators from the University of Texas M.D. Anderson Cancer Center, the expression levels of DICER have global effects on the biogenesis of miRNA, and reduced gene expression correlates with a poor outcome in ovarian cancer. [3] In the M.D. Anderson study, two somatic (i.e., lifetime-acquired) missense DICER mutations were discovered in two epithelial ovarian cancer tumors. The M.D. Anderson investigators concluded that the DICER mutations were not associated with the alterations in DICER expression found in mRNAs. It is important to note that the type of somatic missense DICER mutations discovered in the M.D. Anderson study were not the same as those discovered in the Canadian study as discussed below.

Recurrent DICER Mutations Are Predominant In A Rare Form of Non-Epithelial Ovarian Cancer.

At the outset of the Canadian study, the OvCaRe team sequenced ovarian, uterine, and testicular tumors, expecting to find that their genomes would be distinct with specific, differing abnormalities. Much to their amazement, the researchers discovered that the same fundamental mutation in the DICER1 gene represented a common process underlying the different cancers which they examined.

Specifically, the Canadian investigators sequenced the whole transcriptomes or exomes of 14 nonepithelial ovarian tumors, which included two Sertoli–Leydig cell tumors, four juvenile (not adult) granulosa-cell tumors, and eight primitive germ-cell tumors of the yolk-sac type. The researchers identified closely clustered mutations in the region of DICER1 which encode the RNase IIIb domain in four samples. Based on these findings, the OvCaRe team sequenced the same region of DICER1 in additional ovarian tumors, and tested for the effect of the mutations on the enzymatic activity of DICER1.

Recurrent somatic (i.e., lifetime-acquired) DICER1 mutations in the RNase IIIb domain were identified in 30 of 102 nonepithelial ovarian tumors (29%), including 4 tumors which also possessed germline (i.e., inherited) DICER1 mutations. The highest frequency of somatic DICER1 mutations occurred in Sertoli–Leydig cell tumors (26 of 43, or 60%). Notably, the mutant DICER1 proteins identified in the samples possessed reduced RNase IIIb activity, but retained RNase IIIa activity.

The Canadian researchers also performed additional tumor testing and detected the DICER1 mutations in 1 of 14 nonseminomatous testicular germ-cell tumors, 2 of 5 embryonal rhabdomyosarcomas, and in 1 of 266 epithelial ovarian and endometrial carcinomas.

The groundbreaking nature of this discovery is reflected in the fact that the DICER1 “hotspot” mutations are not present in the 1000 Genomes Project data or the public data repository of The Cancer Genome Atlas consortium. To date, no recurrent DICER1 mutations have been reported in the mutation database of the Catalogue of Somatic Mutations in Cancer (COSMIC), in which 4 of 938 reported cancers possess somatic mutations but none in the RNase IIIb domain hot spots or RNase IIIa equivalents. Moreover, the Canadian researchers note that the newly-discovered DICER1 mutations were not observed in any of the more than 1000 cancer sequencing libraries which were studied.

Based upon the foregoing , the researchers concluded that somatic missense mutations affecting the RNase IIIb domain of DICER1 occur in a range of nonepithelial ovarian tumors, and possibly other cancers. Furthermore, the DICER1 mutations appear to be common in Sertoli-Leydig ovarian tumors (which are a subtype of nonepithelial, sex cord-stromal ovarian tumors). The researchers believe that the recurrent DICER1 mutations identified implicate a novel defect in miRNA processing which does not entirely destroy DICER1 functionality, but alters it.

Accordingly, the Canadian researchers suggest that the newly-discovered DICER1 mutations may represent an oncogenic event within the specific context of nonepithelial ovarian tumors, rather than a permissive event in tumor onset (as may be expected for loss of function in a tumor suppressor gene). The researchers note that DICER1 expression in tumors possessing the hotspot DICER1 somatic mutations argues against a role for DICER1 as a classic tumor suppressor gene. They further explain that the localized and focal pattern of the identified DICER1 mutations is typical of dominantly acting oncogenes, like KRAS and BRAF.

In sum, the Canadian researchers believe that the recurrent and focal nature of the DICER1 mutations and their restriction to nonepithelial ovarian tumors suggest a common oncogenic mechanism associated with a specifically altered DICER1 function that is selected during tumor development in specific cell types.

The Canadian study was supported through funding by Canadian Institutes for Health Research, Terry Fox Foundation, BC Cancer Foundation, VGH & UBC Hospital Foundation, Michael Smith Foundation for Health Research, and Genome BC.

Expert Commentary

“DICER is of great interest to cancer researchers” said Dr. Huntsman, who also holds the Dr. Chew Wei Memorial Professorship in the departments of Obstetrics and Gynecology and Pathology and Laboratory Medicine at UBC. “There have been nearly 1,300 published studies about it in the last 10 years, but until now, it has not been known how the gene functions in relation to cancer.”

“This discovery shows researchers that these mutations change the function of DICER so that it participates directly in the initiation of cancer, but not in a typical ‘on-off’ fashion,” says Dr. Morin who is also assistant professor in the department of Medical Genetics at UBC. “DICER can be viewed as the conductor for an orchestra of functions critical for the development and behavior of normal cells. The mutations we discovered do not totally destroy the function of DICER rather they warp it—the orchestra is still there but the conductor is drunk.”

This finding is the third of a series of papers published recently in the New England Journal of Medicine (NEJM) in which the OvCaRe team used new genomic technologies to unlock the molecular basis of poorly understood types of ovarian cancer. The first finding, published in the NEJM in 2009, identified mutations in the FOXL2 (forkhead box L2) gene as the molecular basis of adult granulosa cell ovarian cancer tumors. The second finding, published in the NEJM in 2010, determined that approximately one-half of clear-cell ovarian cancers and one-third of endometrioid ovarian cancers possess ARID1A  (AT rich interactive domain 1A) gene mutations.

The DICER gene mutation breakthrough discovery is particularly pivotal because it could lead to solutions for treatment of more common cancers.

“Studying rare tumors not only is important for the patients and families who suffer from them but also provides unique opportunities to make discoveries critical to more common cancers – both in terms of personalized medicine, but also in applying what we learn from how we manage rare diseases to more common and prevalent cancers,” said Dr. Huntsman “The discovery of the DICER mutation in this varied group of rare tumors is the equivalent of finding not the needle in the haystack, but rather the same needle in many haystacks.”

Dr. Phillip A. Sharp, Professor, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology; Co-winner of the 1993 Nobel Prize in Physiology and Medicine

“This breakthrough will be of interest to both the clinical and the fundamental science communities,” says Dr. Phillip A. Sharp, Professor, Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology, and co-winner of the 1993 Nobel Prize in Physiology or Medicine for the discovery that genes are not contiguous strings but contain introns, and that the splicing of mRNA to delete those introns can occur in different ways, thereby yielding different proteins from the same DNA sequence. ”Huntsman, Morin and colleagues’ very exciting discovery of specific mutations in DICER, a factor essential for syntheses of small regulatory RNAs in ovarian and other human tumors, could lead to new approaches to treatment.”

The Canadian OvCaRe research team is now working to determine the frequency and role of DICER mutations in other types of cancers. The research team is also expanding its collaboration to discover whether mutant DICER and the pathways it controls can be modulated to treat the rare cancers in which the mutations were discovered and more common cancers.

The Michael Smith Genome Sciences Centre (Michael Smith GSC), located at the BC Cancer agency, played a key role in this discovery. By way of background, Dr. Michael Smith was a co-winner of the 1993 Nobel Prize in Chemistry for his development of oligonucleotide-based site-directed mutagenesis, a technique which allows the DNA sequence of any gene to be altered in a designated manner. His technique created a groundbreaking method for studying complex protein functions, the basis underlying a protein’s three-dimensional structure, and a protein’s interaction with other molecules inside the cell.

A decision was made more than 10 years ago, championed by Drs. Michael Smith, Victor Ling, and others to create and locate the Michael Smith GSC within the BC Cancer Agency and in close proximity to Vancouver General Hospital (VGH). The chosen location for this critical facility provided the multidisciplinary cancer research teams in Vancouver with access to state-of-the-art technologies.

“We are one of less than five places in the world doing this type of work successfully. This discovery is one of a series of recent landmark findings from Vancouver that are reshaping our understanding of many cancers,” says Dr. Huntsman. “Since my arrival in Vancouver 20 years ago I have never before sensed such a strong feeling of communal pride and excitement within our research community. Our next task is to bring the discoveries into the clinic.”

About the Ovarian Cancer Research Program of British Columbia (OvCaRe)

OvCaRe is a multidisciplinary research program involving clinicians and research scientists in gynecology, pathology, and medical oncology at VGH and BC Cancer Agency. OvCaRe is a unique collaboration between the BC Cancer Agency, Vancouver Coastal Health Research Institute, and UBC. The OvCaRe team is considered a leader in ovarian cancer research which is breaking new ground in better identifying, understanding, and treating this disease. The OvCaRe seminal paper in PLoS (Public Library of Science), which addresses ovarian cancer as a group of distinct diseases, has been embraced by the global research community who has adopted the BC approach to ovarian cancer research. To learn more, visit www.ovcare.ca.

About the Michael Smith Genome Sciences Centre

Canada’s Michael Smith Genome Sciences Centre is an internationally recognized state-of-the-art facility applying genomics and bioinformatics tools and technologies to cancer research. Led by Dr. Marco Marra, the Michael Smith GSC is one of ten leading genomic research centres in the world and the only one of its kind in the world integrated into a cancer facility. With a primary focus on cancer genomics research, its scientists have been involved in many world-class groundbreaking discoveries over the past decade. To learn more, visit www.bcgsc.ca.

About the Vancouver Coastal Health Research Institute

Vancouver Coastal Health Research Institute is the research body of Vancouver Coastal Health Authority, which includes BC’s largest academic and teaching health sciences centres: Vancouver General Hospital, UBC Hospital, and GF Strong Rehabilitation Centre. The institute is academically affiliated with the UBC Faculty of Medicine, and is one of Canada’s top-funded research centres, with $82.4 million in research funding for 2009/2010. To learn more, visit www.vchri.ca.

About the British Columbia Cancer Agency

The BC Cancer Agency, an agency of the Provincial Health Services Authority, is committed to reducing the incidence of cancer, reducing the mortality from cancer, and improving the quality of life of those living with cancer. It provides a comprehensive cancer control program for the people of British Columbia by working with community partners to deliver a range of oncology services, including prevention, early detection, diagnosis and treatment, research, education, supportive care, rehabilitation and palliative care. To learn more, visit www.bccancer.ca.

About the University of British Columbia

The University of British Columbia is one of North America’s largest public research and teaching institutions, and one of only two Canadian institutions consistently ranked among the world’s 40 best universities. Surrounded by the beauty of the Canadian West, it is a place that inspires bold, new ways of thinking that have helped make it a national leader in areas as diverse as community service learning, sustainability, and research commercialization. UBC offers more than 55,000 students a range of innovative programs and attracts $550 million per year in research funding from government, non-profit organizations, and industry through 7,000 grants. To learn more, visit www.ubc.ca.

References

1/Morin G, Hunstman, DG et al.  Recurrent Somatic DICER1 Mutations in Nonepithelial Ovarian Cancers. NEJM, published online December 21, 2011 (10.1056/NEJMoa1102903).

2/The Canadian investigators describe the operation of the RNAi pathway with respect to miRNA biogenesis as follows:

“MicroRNAs (miRNAs) are a functional class of noncoding RNA molecules that regulate translation and degradation of messenger RNA. MiRNA transcripts are processed from hairpin pre-miRNA precursors into short miRNA:  miRNA* duplexes consisting of the miRNA targeting strand and the imperfectly complementary miRNA* strand (star strand, or inert carrier strand) by Dicer, an endoribonuclease with two RNase III–like domains. The RNase IIIb domain cuts the miRNA strand, whereas the RNase IIIa domain cleaves the miRNA* strand. The resultant RNA duplex is loaded into the RNA-induced silencing complex (RISC) containing an Argonaute protein. The miRNA* strand is then removed, leaving the miRNA strand, which targets messenger RNAs (mRNAs) for degradation or interacts with the translation initiation complex to inhibit and destabilize translation of the targeted messenger RNAs.” [footnote citations omitted]

3/Merritt WM, et al. Dicer, Drosha, and outcomes in patients with ovarian cancer. N Engl J Med. 2008 Dec 18;359(25):2641-50. Erratum in: N Engl J Med. 2010 Nov 4;363(19):1877. PubMed PMID: 19092150; PubMed Central PMCID: PMC2710981.

Sources:

• Gene links rare and unrelated cancers — An important breakthrough in cancer research, Joint Press Release, BC Cancer Agency, Vancouver Coastal Health Research Institute, and the University of British Columbia, December 21, 2011.

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.