At the third in a series of Congressional hearing on conflicts of interest at the National Institutes of Health (NIH), NIH Director Dr. Elias A. Zerhouni last week announced further changes to strengthen agency ethics policies. Speaking before the House Energy and Commerce Subcommittee on Oversight and Investigations, Dr. Zerhouni explained that the changes are rooted in four principles: enhancing the public trust, increasing transparency, recruiting and retaining the best scientific expertise while expediting the translation of research advances, and establishing effective monitoring and oversight mechanisms.

The announcement followed NIH's continued review of its ethics program and policies, as well as findings from an investigation by the subcommittee of more than 100 consulting or other arrangements between industry and NIH scientists that had not been reported to NIH ethics officials.

"I have reached the regrettable conclusion that drastic changes are needed," Dr. Zerhouni said. "In retrospect, there was not sufficient safeguard against the perception of conflict of interest."

Among the proposed changes to the NIH ethics policy is a total ban on paid consulting arrangements between senior NIH officials and industry, a ban on the receipt of stock or stock options by all NIH employees as compensation from industry, a limit on consulting fees that certain NIH scientists can receive from industry and on the number of hours they can spend working on such arrangements, and a ban on all NIH employees receiving any form of payment from any institutions that receive NIH funding for research. The creation of a centralized database that contains all outside collaborations for NIH employees is also being considered, Dr. Zerhouni explained.

Some subcommittee members suggested that a total prohibition on outside consulting activities may be the only way to truly eliminate any perception of a conflict of interest at NIH. Such a move, Dr. Zerhouni responded, would have a detrimental effect on the NIH and its employees.

Three NCI senior staff participated in the hearing: Dr. J. Carl Barrett, director of the Center for Cancer Research; Dr. Anna D. Barker, deputy director for advanced technology and strategic partnerships; and Dr. Maureen O. Wilson, assistant director and deputy ethics counselor.

The subcommittee sought additional information on an NCI scientist's consulting arrangement with a California-based life sciences company from the NCI officials who had approved the activity. The witnesses responded to questions about the approval process and suggested that reforms to the system, such as those proposed by Dr. Zerhouni, are likely to prevent future conflicts. NCI has committed to taking the necessary steps to support the highest standards of ethics and recognized standards of scientific excellence. Dr. Wilson has noted that efforts are underway to educate NCI staff on their responsibilities as federal employees in order to avoid any real or apparent conflicts of interest in the future.

In a message to staff last week, NCI Director Dr. Andrew C. von Eschenbach said he shares Dr. Zerhouni's "concern about the potential erosion of public trust" brought on by these hearings and that he strongly endorsed transparency.

"Along with NIH, NCI will take actions to clarify its rules and policies and look at ways to improve our ethics program as it relates to federal employees' relationships with outside organizations," he said.

NCI is in the process of linking its many databases so that proposed outside activities by NCI staff can be cross-referenced easily against any grant, contract, or other agreement that the institute may have with an outside organization. Local briefing sessions with NCI staff will also be held, Dr. von Eschenbach said, to explain and discuss ethics rules and policies.

For the National Cancer Institute (NCI), June has been a month of great excitement and progress in cancer survivorship research. Cancer Survivors' Day and the release of the President's Cancer Panel report, Living Beyond Cancer: Finding a New Balance, kicked off the month. Mid-month, we awarded 17 new grants to study long-term cancer survivors and cohosted with the American Cancer Society (ACS) our second biennial conference, "Pathways to Health After Treatment." To conclude the month, we reported new survivor prevalence data in the Annual Report to the Nation on the Status of Cancer ² and in last week's Morbidity and Mortality Weekly Report ³ from the Centers for Disease Control and Prevention (CDC). At the core of all these activities lies a common premise: Cancer survivors are experiencing longer survival, thus attention to their quality of life is imperative.

Once almost uniformly fatal, cancer has become for most people a chronic illness, and for growing numbers, a curable disease. In the absence of other competing causes of death, current figures indicate that for adults diagnosed today, 64 percent can expect to be alive in 5 years. Almost 79 percent of childhood cancer survivors will be alive at 5 years, and 10-year survival is approaching 75 percent. As advances in cancer detection, treatment, and care diffuse into clinical practice and as the current population ages, the number of survivors can be expected to increase.

The steadily increasing number of cancer survivors is a testament to the many successes achieved by the cancer community. These include progress in the development and use of cancer screening and early detection technologies, more effective and often multimodal therapies, and a broadening array of supportive care and rehabilitative options. Increased survivorship also results from wider adoption of cancer screening behaviors and healthier lifestyles by those at risk for the disease. At the same time, the 9.8 million survivors in the United States represent a clear challenge to NCI. These individuals serve as a reminder that we must look beyond the search for a cure and provide hope for a productive and valuable future to those living with and beyond a cancer diagnosis.

Cancer survivors face issues such as maintaining optimal physical and mental health, preventing disability and late effects related to cancer and its treatment, and ensuring social and economic well-being for themselves and their families. The 17 grants to study long-term survivors will begin to address many of these issues.

The studies will examine areas such as health care utilization after treatment, the impact of newer cancer therapies on quality-of-life outcomes, the incidence and nature of metabolic syndromes among childhood and adult cancer survivors, and interventions to ameliorate adverse outcomes among those living with unfavorable consequences of their disease or its treatment. Investigators will address these questions with special awareness of and focus on previously understudied populations including people who have survived colorectal, head and neck, gynecologic, or hematologic cancers; the elderly; and people from diverse sociocultural backgrounds. These grants will enable us to create a strong, multidisciplinary cadre of investigators positioned to enhance the scientific and methodological basis of this quickly maturing area of scientific inquiry.

NCI could not be at the forefront of survivorship research without innovative collaborations with partners such as CDC, ACS, the National Coalition for Cancer Survivorship, and the Lance Armstrong Foundation. With their support and dedication, NCI's Office of Cancer Survivorship ⁵ is uniquely poised to champion significant advances in cancer survivorship research.

Dr. Julia H. Rowland
Director, Office of Cancer Survivorship
Division of Cancer Control and
Population Sciences

Most Women Do Not Have Recommended Annual Mammograms

Regardless of age, race, ethnicity, income, language, insurance, previous screening use, medical history, or zip code - only 6 percent of women get regular annual mammograms, according to a study in the June 21 online issue of Cancer.

The study included data on 72,417 women who received a total of 254,818 screening mammograms. Dr. James Michaelson and his team at the Massachusetts General Hospital's Avon Foundation Comprehensive Breast Evaluation Center found that only 6 percent of women who received a mammogram in 1992 received all recommended annual screenings for the next 10 years. Researchers noted that this shows "a screening level that was disappointingly low, with potentially negative health-related consequences."

Women aged 55-64 and women with previous breast cancer had higher screening rates than other women. All groups fell within the low screening range, but women without insurance, women who did not speak English, and women from traditionally underserved groups had lower screening rates than other women.

The authors note that in their screening population approximately 20 percent of all invasive breast malignancies detected in women who had been screened previously were found by non-mammographic methods more than a year after the previous negative mammography. "Most of these tumors probably emerged as larger, palpable masses not because a previous mammogram failed to detect them but because too much time had been allowed to pass since the last screening mammogram," the authors conclude.

Blood Vessel Membrane Proteins Help Target Imaging Agents and Drugs

Proteomic research holds great promise for cancer diagnosis and treatment, but a vast number of proteins must be catalogued. With that in mind, Dr. Phil Oh led researchers from the Sidney Kimmel Cancer Center in San Diego in identifying proteins in the inner surface of blood vessels in the rat lung. They found that two membrane proteins, aminopeptidase-P and annexin A1, can be targeted with antibodies to image and destroy lung tumors. Their results are published in the June 10 issue of Nature.

Scientists have previously seen that blood cells slow, roll along, and stop at specific points in the circulatory system. Dr. Oh and his team proposed that this process is triggered by something on the surface of blood vessel cells. The research team infused the blood of rats with colloidal silica to "paint" the inner surface of blood vessel cell membranes. They then separated these portions of the membrane by centrifuge and used radiolabeled antibodies to distill the pool of proteins from hundreds of thousands to 11 that were most likely in the lumen.

Researchers identified the proteins with the highest expression in blood vessels feeding the tumors of the lung, including aminopeptidase-P and annexin A1. They tested the reliability of these two targets by infusing the rats with radiolabeled antibodies. This showed rapid and specific targeting of blood vessels feeding the tumors, as well as remission in rats that received the radiolabeled annexin A1.

Smoking Cessation Can Add 10 Years to Life Expectancy

Men in the United Kingdom who smoke cigarettes throughout their life die an average of 10 years earlier than lifelong nonsmokers, according to the results of a 50-year study published in the June 22 issue of the British Medical Journal. Those who quit at age 60, 50, 40, or 30 gained about 3, 6, 9, or 10 years of life expectancy, respectively. This research began in 1951 as a prospective study of smoking mortality in 31,496 British doctors.

The study also found that physicians born between 1910 and 1920 had a much higher smoking mortality in middle age than those who were born in the first decade of the 20th century - likely because their generation was affected by military service during World War II, when cigarette provisions provided more intense early exposure.

In a 1994 article, published at the study's 40-year mark, the authors stated that approximately one-half of lifelong cigarette smokers will eventually be killed by their habit. This article now adds that the risk can be as great as two-thirds, stating that "[based] on current worldwide smoking patterns…there will be about one billion tobacco deaths in this century, unless there is widespread cessation."

Teen Smoking Reaches Record Low, CDC Reports

The number of American teenagers who smoke cigarettes has reached an all-time low, according to recent results from the national Youth Risk Behavior Survey by CDC. The analysis appeared in the June 18 Morbidity and Mortality Weekly Report.

The current analysis assessed three behaviors: 1) lifetime cigarette use (ever tried cigarette smoking); 2) current use (smoked on 1 or more of the 30 days preceding the survey); and 3) current frequent use (smoked on 20 or more of the 30 days preceding the survey).

Study results showed that prevalence of current use declined from 36.4 percent in 1997 to 21.9 percent in 2003. The prevalence of current frequent use also declined from 16.8 percent in 1999 to 9.7 percent in 2003. Prevalence of current use among males and females was similar, with males' use at 21.8 percent and females' use at 21.9 percent in 2003. Prevalence of current use by grade level in 2003 was: grade 9 - 17.4 percent; grade 10 - 21.8 percent; grade 11 - 23.6 percent; grade 12 - 26.2 percent.

CDC cited three factors that might have contributed to the decline in cigarette use: 1) a 90 percent increase in the retail price of cigarettes during December 1997-May 2003; 2) increases in school-based efforts to prevent tobacco use; and 3) increased exposure of young people through the mass media to smoking prevention campaigns funded by states or the American Legacy Foundation.

CDC also noted that while this decline is encouraging, prevention efforts must be sustained if the nation is to reach its 2010 national health objective of reducing the prevalence of current cigarette use among high school students to 16 percent or less.

More than 100 churches in the Miami-Dade County, Florida area participate in a community health program called Healthy Body, Healthy Soul, aimed at health promotion and disease prevention activities. Administered by the Health Choice Network (HCN), it's having a significant effect on healthy behavior change.

"In the past, a church event might have included a lot of high-fat foods, but now we see more fruits and vegetables and fewer sodas," says Rev. Ted Greer, who heads up the Jesse Trice Cancer Prevention Project, which is part of the Healthy Body, Healthy Soul program. And pastors like Rev. Greer are leading by example. "When we schedule a health fair at one of our churches, the pastor leads the line," he says. "That's powerful. The congregation usually follows, because it's not just someone lecturing them.

"Healthy Body, Healthy Soul is a grassroots movement to reach out to minority groups and educate them about cancer prevention and healthy lifestyles. Despite efforts to make health care available to everyone, there is still a difference in minorities' cancer health outcomes and access to primary and preventive health services compared to whites. Some of these disparities can sometimes be overcome when health promotion messages come from within the community itself. HCN is a good example.

HCN is a group of community health center corporations that operates primary health care and mental health clinics in four states. In Florida, HCN reaches more than 170,000 patients. Forty-four percent are Hispanic and 30 percent are black; 69 percent are at or below the federal poverty level.

HCN clinic staff train local congregation members to conduct health and education activities at their churches. The program not only improves the health of individuals, but also develops the community's capacity to sustain its own health promotion efforts.

The Jessie Trice Cancer Prevention Project, named after a nurse and community health advocate who died of lung cancer, provides prevention education, smoking cessation, and screening services for early detection of lung, prostate, breast, and cervical cancers.

Rev. Greer says that the keys to this program's success are access to medical care for patients and access to the community through churches. "We pastors used to talk about God's ability to heal, but we never talked about prevention," he says. "This program gives us the opportunity to do that."

The project has screened more than 5,000 patients and identified 3 cases of stage I lung cancer. An additional 75 residents are being monitored to make sure that, if they do develop cancer, it's identified early. More than 3,000 teens and young adults have received smoking prevention and cessation services, and 100 have completed smoking cessation classes.

For more information about the Health Choice Network, go to www.hcnetwork.org.

The House Energy and Commerce Subcommittee on Health held a hearing on June 2, titled "Scientific Opportunities and Public Needs: Balancing NIH's Priority Setting Process." This was the fifth in a series of hearings designed to highlight research activities at the NIH. The goal of these hearings is to educate members of Congress about NIH's work so that the committee can assess how to help the agency better meet its mission.

Subcommittee Chairman Michael Bilirakis (R-Fla.) stated that members need to understand how the NIH chooses what research to conduct and how that research is funded. Ranking Subcommittee Member Sherrod Brown (D-Ohio) stated that most members have tried to steer clear of efforts to compromise the flexibility NIH has to allocate its resources.

Rep. Joe Barton (R-Texas), chairman of the House Committee on Energy and Commerce, stated that he wants "the most effective, state-of-the-art NIH for the 21st century that gets the biggest bang for the taxpayers' bucks and the private sector dollars that are coordinated with what NIH does."

Invited to present testimony at this hearing were NIH Director Dr. Elias Zerhouni and the directors of NCI, the National Institute of Allergy and Infectious Diseases, and the National Institute on Drug Abuse. Dr. Zerhouni noted that NIH's goal is "to reduce both the disease burden as we know it today and the potential disease burden as it may occur in the future." He explained how NCI uses the Surveillance, Epidemiology, and End Results (SEER) program to track America's cancer burden.

NCI Director Dr. Andrew C. von Eschenbach told the committee how mortality rates from cancer were declining due to the progress in biomedical research and that achieving the 2015 goal of eliminating suffering and death from cancer will necessitate establishing priorities and investments that are required to achieve this goal. He described the balance of NCI's research portfolio across the discovery, development, delivery continuum, and then explained how the portfolio is managed by a decision- making process that includes external input at multiple points in the process.

The concluding discussion centered on questions about how to optimize the structure of NIH, specifically, whether Congress should reorganize the NIH through legislation or NIH should be given some institutional authority to restructure. Each of the witnesses had the opportunity to offer an opinion; Dr. von Eschenbach suggested that NIH structure should be driven by function and supported, giving the NIH director flexibility to advocate interaction among institutes and centers when appropriate.

SBIR/STTR: Circulating Cells and DNA in Cancer Detection

RFA-CA-06-001
Letter of Intent Receipt Dates: Jan. 17, 2005; May 16, 2005; Sept. 14, 2005
Application Receipt Dates: Feb. 14, 2005; June 13, 2005; Oct. 12, 2005

NCI's Division of Cancer Prevention invites small business applications for research projects to develop novel technologies for capturing, enriching, and preserving exfoliated abnormal cells and circulating DNA from body fluids or effusions and to develop methods to concentrate these cells and DNA for cancer biomarker detection.

This RFA will use the SBIR and STTR mechanisms.

For more information see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=2124

Inquiries: Dr. Sudhir Srivastava, ss1a@nih.gov

Exfoliated Cells, Bioactive Food Components, and Cancer

PA-04-114
Application Receipt Dates: July 1, 2004; Nov. 1, 2004; March 1, 2005; July 1, 2005; Nov. 1, 2005; March 1, 2006; July 1, 2006; Nov. 1, 2006; March 1, 2007; July 1, 2007; Nov. 1, 2007

NCI invites applications for new grants that focus on research to critically evaluate the use of exfoliated cells to monitor the physiological effects of dietary bioactive food components thought to be involved with cancer prevention. The objective is to encourage interdisciplinary collaborations between scientists engaged in research using exfoliated cells and those conducting nutrition research related to cancer prevention.

This research will help determine the utility of exfoliated cells as a model system to monitor both the absorption and retention of bioactive food components and the concomitant alterations in genomic and epigenetic events that occur in intact cells.

This PA will use the NIH Investigator-Initiated Research Project Grant (R01), the NIH Exploratory/ Developmental grant (R21), and the NIH Small Grants Program (R03) as award mechanisms.

For more information see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=2142

Inquiries: Dr. Cindy D. Davis, davisci@mail.nih.gov; Dr. Virginia W. Hartmuller, hartmulv@mail.nih.gov

Understanding and Promoting Health Literacy (R01)

PAR-04-116
Letter of Intent Receipt Dates: Sept. 13, 2004; Sept. 13, 2005; Sept. 13, 2006
Application Receipt Dates: Oct. 13, 2004; Oct. 13, 2005; Oct. 13, 2006

The goal of this PA is to increase scientific understanding of the nature of health literacy and its relationship to healthy behaviors, illness prevention and treatment, chronic disease management, health disparities, risk assessment of environmental factors, and health outcomes including mental and oral health. Such knowledge will help enable health care and public health systems to serve individuals and populations more effectively and to employ strategies that reduce health disparities in the population.

This PA will use the R01 award mechanism.

For more information see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=2140

Inquiries: Dr. Sabra Woolley, woolleys@mail.nih.gov; Dr. Gary L. Kreps, Gary.Kreps@nih.gov

Understanding and Promoting Health Literacy (R03)

PAR-04-117
Letter of Intent Receipt Dates: Sept. 13, 2004; Sept. 13, 2005; Sept. 13, 2006
Application Receipt Dates: Oct. 13, 2004; Oct. 13, 2005; Oct. 13, 2006

The goal of this PA is to increase scientific understanding of the nature of health literacy and its relationship to healthy behaviors, illness prevention and treatment, chronic disease management, health disparities, risk assessment of environmental factors, and health outcomes including mental and oral health. Such knowledge will help enable health care and public health systems to serve individuals and populations more effectively and to employ strategies that reduce health disparities in the population.

This PA will use the NIH R03 award mechanism.

For more information see http://cri.nci.nih.gov/4abst.cfm?initiativeparfa_id=2141

Inquiries: Dr. Sabra Woolley, woolleys@mail.nih.gov; Dr. Gary L. Kreps, Gary.Kreps@nih.gov

Name of the Trial
Genetic and Etiology Study of Cancer Susceptibility in Patients and Their Families With Fanconi's Anemia or Other Inherited Disorders of the Bone Marrow (NCI-02-C-0052). See the protocol summary at http://cancer.gov/clinicaltrials/NCI-02-C-0052.

Principal Investigator
Dr. Blanche Alter of NCI's Division of Cancer Epidemiology and Genetics

Why Is This Trial Important?
Inherited bone marrow failure syndromes (IBMFS) are rare disorders in which the bone marrow fails to adequately produce blood cells. Persons with these syndromes tend to have a very high risk of developing acute leukemia or certain solid tumors, such as head and neck, vulvar, and cervical tumors.

NCI scientists are assembling a study population that includes IBMFS patients and their family members. Researchers want to determine the number of existing cases of cancer in this population, which specific types of cancers are associated with each type of IBMFS, and at what rate IBMFS patients develop cancer. They also hope to identify specific genetic mutations associated with each IBMFS and relate these mutations to cancer risk.

"We hope to help those individuals who have these syndromes by targeting cancer screening/surveillance programs, by avoiding potential carcinogenic exposures such as tobacco, and by avoiding modes of cancer therapy that might be toxic, such as radiation and some forms of chemotherapy," said Dr. Alter.

Who Can Join This Trial?
Researchers seek to enroll up to 1,000 participants (patients and family members) in families with a suspected or proven diagnosis of an IBMFS. See the full list of eligibility criteria for this trial at http://cancer.gov/clinicaltrials/NCI-02-C-0052.

Where Is This Trial Taking Place?
This study is taking place at the National Institutes of Health Warren G. Magnuson Clinical Center in Bethesda, Md.

Who to Contact
For more information, visit the study's Web site at www.marrowfailure.cancer.gov or call the NCI Clinical Studies Support Center (CSSC) at 1-888-NCI-1937. CSSC provides information about cancer trials taking place on the NIH campus. The call is toll free and confidential.

CCR Grand Rounds July 6: Dr. Ronald E. Gress of NCI's Center for Cancer Research will present "The Interface of Cancer Immunotherapy and Chemotherapy." July 13: NCI Director Dr. Andrew C. von Eschenbach will present "Progress toward Eliminating the Suffering and Death Due to Cancer." CCR Grand Rounds are held 8:30 to 9:30 a.m. at the NIH campus in Bethesda, Md., in the Clinical Center's Lipsett Amphitheater.

At the meeting, BSA members heard reports from the NCI director and various NCI offices. In addition, NCI staff presented information on a number of new and ongoing programs. The Board provided concept review for new and re-issued projects including assessment of tobacco products promoted to reduce harm, nanotechnology, and partnerships between minority institutions and cancer centers.

Watch for more coverage of the BSA meeting in an upcoming issue of the NCI Cancer Bulletin.

NCI Health Communications Interns Graduate
On June 24, Nelvis Castro, acting director of the NCI Office of Communications, bid farewell to NCI's graduating class of health communication interns. NCI's Health Communication Internship Program offers 6-month internships in health communications and science writing. The interns serve from January through June or July through December. Applications for internships beginning in January 2005 are due by September 15, 2004. For more information on the program and for application materials and eligibility requirements, go to http://internship.cancer.gov.

Translating Research Into Practice
Translating Research Into Practice (TRIP) will take place July 12-14 in Washington, D.C. This national conference will examine state-of-the-art practice and future directions for disseminating research findings to accelerate the implementation of evidence-based clinical practice and health policy. Dr. Mark Clanton, NCI deputy director of Cancer Care Delivery Systems, will deliver a keynote address. Other NCI-related sessions include "The Curious Contradiction of Colorectal Cancer Screening vs. PSA Testing" and "Evidence-Based Tobacco Cessation Interventions for Underserved Populations." TRIP is cosponsored by the Agency for Healthcare Research and Quality, NCI, and the Department of Veterans Affairs, with support from the Substance Abuse and Mental Health Services Administration, the National Institute of Mental Health, and the National Institute on Drug Abuse. For the conference agenda, registration, and hotel reservations, go to www.blsmeetings.net/TRIP2004.

Zoon Moves to NIAID from NCI
NCI's Dr. Kathryn Zoon has left NCI to join the National Institute of Allergy and Infectious Diseases, where she will serve as deputy director for Planning and Development. Dr. Zoon joined NCI's Center for Cancer Research Metabolism Branch in January 2003, where she served as principal deputy director and principal investigator. Prior to her tenure at NCI, Dr. Zoon served as director of the U.S. Food and Drug Administration's Center for Biologics Evaluation and Research from 1992 to 2002.