National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
May 18, 2010 • Volume 7 / Number 10


President to Appoint Dr. Harold Varmus to Lead NCI

Yesterday, President Barack Obama announced his intent to appoint Dr. Harold Varmus to serve as director of the National Cancer Institute.

In an e-mail to the NCI staff yesterday, Director of NIH Dr. Francis Collins said that Dr. Varmus "brings unmatched expertise at all levels—not only in cutting edge scientific research, but also as a leader in the development of strategies for improving patient care, in scientific education and training, and in the design of novel public-private partnerships."

For additional coverage of this important development, be sure to read upcoming issues of the NCI Cancer Bulletin.


Director's Update: For Clinical Trials, a Time of Challenge, Change, and Opportunity

Last month, the prestigious Institute of Medicine released a report on clinical trials for cancer. That report, A National Cancer Clinical Trials System for the 21st Century, discusses weaknesses of the Cooperative Group clinical trials system supported by NCI, and it includes four recommendations suggesting, among other items, that NCI improve the speed and efficiency of clinical trials, incorporate more innovative science into trial design, improve the prioritization of trials so that more trials are run to completion, and find incentives to encourage patients and physicians to participate. Read more > >

Watch the Inside NCI video

Inside NCI: A Conversation with Dr. Jeff Abrams about Cancer Clinical Trials

The associate director of NCI's Cancer Therapy Evaluation Program discusses some of the challenges and opportunities in coordinating the largest publicly funded oncology clinical trials organization in the world. Read more > >


Cancer Trials Accrual Tool Focuses on Solutions

NCI researchers last month unveiled a new online tool for clinicians and professionals who recruit people to join cancer clinical trials. The tool, called AccrualNet, is both a repository of information and a forum for professionals to exchange ideas about the challenges associated with developing and managing these important studies. Read more > >




  • Legislative Update

    • Cures Acceleration Network Featured at Senate Appropriations Subcommittee Hearing
  • Update

    • Recovery Act Web Site Highlights NCI Clinical Proteomic Technologies for Cancer Initiative
  • Notes

    • PLCO EEMS Seeks Applicants
    • Enter the Celebrating Smokefree Voices Video Contest
    • Meet NCI Experts at ASCO
    • Abstracts Accepted for the Molecular Markers in Cancer Meeting
    • President's Cancer Panel Issues Report on Environmental Cancer Risks
    • Updated NCI Spanish-language Booklet on Breast Cancer

Selected articles from past issues of the NCI Cancer Bulletin are available in Spanish.

The NCI Cancer Bulletin is produced by the National Cancer Institute (NCI), which was established in 1937. Through basic, clinical, and population-based biomedical research and training, NCI conducts and supports research that will lead to a future in which we can identify the environmental and genetic causes of cancer, prevent cancer before it starts, identify cancers that do develop at the earliest stage, eliminate cancers through innovative treatment interventions, and biologically control those cancers that we cannot eliminate so they become manageable, chronic diseases.

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Special Issue: Clinical Trials Enrollment

Director's Update: For Clinical Trials, a Time of Challenge, Change, and Opportunity

Dr. John E. Niederhuber Dr. John E. Niederhuber

Last month, the prestigious Institute of Medicine released a report on clinical trials for cancer. That report, A National Cancer Clinical Trials System for the 21st Century, discusses weaknesses of the clinical trials system supported by NCI, and it includes four recommendations suggesting, among other items, that NCI improve the speed and efficiency of clinical trials, incorporate more innovative science into trial design, improve the prioritization of trials so that more trials are run to completion, and find incentives to encourage patients and physicians to participate.

A critique of the Cooperative Groups, which suggests a large organization with a history dating back half a century must do better, might be a bitter pill to swallow. But not in this case. NCI requested this report and funded its development. Furthermore, the Institute of Medicine’s report echoes strategies already being implemented by NCI. My only concern is that perhaps the report did not go far enough in recognizing the need for some fairly radical changes—for example, creating a national “virtual cohort” of highly characterized patients prescreened for participation in clinical studies, a vision I have espoused a number of times this year. These changes, I believe, will be required to conduct the highly targeted, multi-agent trials of the future.

In 2005, NCI received the report of its Clinical Trials Working Group, and 2 years later, the Translational Research Working Group presented its report as well. Since then, NCI has been working diligently to synthesize and implement important changes in the way we translate discoveries to public health benefit. We have instituted the Clinical Trials and Translational Research Advisory Committee, which is helping guide NCI’s efforts to streamline and hasten trials. In addition, NCI’s Operational Efficiency Working Group, which oversees and coordinates the majority of NCI-supported trials, recently rolled out a set of recommendations on clinical trials, which the Institute of Medicine report strongly endorsed.

Clearly, there are a number of issues we must confront, not the least of which is physician reimbursement. Quite simply, what NCI currently pays to support clinical trials does not cover their costs. Moving forward, and cognizant of the limited resources NCI can bring to bear, it may be necessary to fund fewer trials in order to increase reimbursement and to also adequately support the costly and complex correlative science that will be mandatory for a successful trial.

Another issue is clinical trials participation, which among adults remains distressingly low. While there are many issues that affect accrual, I am reminded of the comment my wife made during her struggle with advanced breast cancer. The problem, she said, isn’t patients. “The problem is that your trials aren’t very exciting.” It is my hope that the new era of technology-enabled medicine will change this situation. Now we have the opportunity, by characterizing our patients, to intelligently show them why the trial of a novel agent is tailored specifically to their cancer—which should be exactly the boost our trials system needs to recruit more patients.

This special issue of the NCI Cancer Bulletin is a small component of our efforts to improve trial accrual. In it we review the landscape of clinical trials recruitment and consider ways to improve the process, including important efforts to overcome accrual barriers, which include disparities in access to trials, difficulties in getting insurers to cover the costs of routine care provided in trials, and developing and sharing best practices for improving the efficacy of the entire recruitment and accrual process.

On this latter point, it is heartening to see the launch of AccrualNet, a new NCI resource more than 2 years in the making that I am confident will become an invaluable tool for health care professionals who promote and manage enrollment in clinical trials.

A number of other initiatives will hasten the development of therapeutics and their testing in human trials, including programs such as NExT and ACTNOW, both of which are focused on improving the efficiency and effectiveness of developing targeted drugs and testing them in early-phase clinical trials. Along those lines, NCI is working with investigators to incorporate predictive biomarkers into nearly all of our phase III trials, while also promoting the development and use of adaptive design trials, like the recently launched I-SPY2 trial.

Of course, a targeted therapy can only be effective if the patient’s tumor expresses that molecular target. With NCI’s Program for the Assessment of Clinical Cancer Tests, the Institute is providing tools and resources for investigators and industry to develop companion diagnostics: high-quality assays that can accurately identify patients whose tumors bear molecular markers that indicate they are more likely to respond to a given therapy. These assays should lead to smaller, less expensive trials that are more likely to show a clinical benefit.

While there are a great many complex issues to resolve, I believe the greatest difficulty we face is devilishly simple. We must be prepared to adequately answer one simple question: Why should I take part in a clinical trial? The articles in this edition of the NCI Cancer Bulletin provide a strong answer.

Dr. John E. Niederhuber
Director, National Cancer Institute

Special Issue: Clinical Trials Enrollment

Inside NCI: A Conversation with Dr. Jeff Abrams about Cancer Clinical Trials

The associate director of NCI's Cancer Therapy Evaluation Program discusses some of the challenges and opportunities in coordinating the largest publicly funded oncology clinical trials organization in the world.

Special Issue: Clinical Trials Enrollment

Cancer Trials Accrual Tool Focuses on Solutions

An illustration showing that AccrualNet provides support at every stage of a clinical trial, from planning to recruiting and treating patients to closing the trial and analyzing the data. AccrualNet provides support at every stage of a clinical trial, from planning to recruiting and treating patients to closing the trial and analyzing the data. [Enlarge]

NCI researchers last month unveiled a new online tool for clinicians and professionals who recruit people to join cancer clinical trials. The tool, called AccrualNet, is both a repository of information and a forum for professionals to exchange ideas about the challenges associated with developing and managing these important studies.

AccrualNet was introduced at the Cancer Trial Accrual Symposium, held April 29–30 in Bethesda, MD. The conference, hosted by NCI and the American Society of Clinical Oncology, attracted more than 350 leaders and representatives from organizations actively engaged in clinical trial recruitment.

The meeting was dedicated to building the science behind accrual. Much has been learned in recent years about how to recruit patients to trials and support these patients while they go through treatment. But much of that information resides only in the minds of those who have conducted clinical trials, and what has been documented in the scientific literature is scattered.

A potential solution to this problem is AccrualNet. The tool aggregates knowledge about clinical trials and makes this information available to professionals in the field. The Web site features a searchable, annotated list of journal articles on clinical trial recruitment and links to relevant publications, such as a guide to informed consent and a study of attitudes toward clinical trials within the African American community.

“AccrualNet is a repository of information and resources that has never existed before,” said lead developer Dr. Holly Massett of NCI’s Office of Communications and Education. “At the same time, the tool will allow people to interact and share ideas about clinical trial accrual.”

Dr. Massett and her team began researching the project in early 2008. The goals were to understand the landscape of information on clinical trial recruitment and to identify what was missing. The researchers interviewed a variety of stakeholders and visited community oncology practices as well as NCI-designated comprehensive cancer centers.

Several themes emerged from the interviews. “People struggle to find information about clinical trial accrual,” said Dr. Massett. “Over and over again we heard people say: ‘If only the accrual resources were in one place.’ Another common refrain was: ‘I wish I could talk to other people about accrual.’”

Based on these findings, the researchers developed a prototype of AccrualNet. Information and resources were identified for each stage of a trial, from pre-study planning to the active phase and post-study evaluations. As the Web site notes, “At every stage, recruiting issues matter.”

Extensive user testing revealed a strong desire among many professionals to be able to connect with colleagues and share resources and tips. The developers created a “community of practice” that allows users to contribute materials, tips, experience, and information about best practices. Users can also offer comments on materials.

AccrualNet also allows professional groups to create a forum where they can have discussions about topics of interest on the site. For example, administrators in the Community Clinical Oncology Program have set up a group for discussions.

The project’s main goal is to increase knowledge about the processes needed for success in clinical trial accrual. Another is to encourage the use of available literature and resources in planning and conducting recruitment activities.

Beyond these immediate goals, the project could help identify gaps in the research around accrual strategies and define future research questions.

AccrualNet is designed to grow along with the science behind accrual, and it currently shares the limitations of the field. Much of the evidence consists of reports from single institutions, and there are few randomized controlled studies (considered the gold standard of evidence) on accrual and retention.

“AccrualNet is a starting point,” noted Dr. Massett. “But it has the potential to be a framework for how we look at accrual in cancer clinical trials moving forward.” 

AccrualNet is just one of many projects aimed at achieving the important accrual goals that were presented during the Cancer Trial Accrual Symposium. Slides and information on some of the presentations are now available.

—Edward R. Winstead

Special Issue: Clinical Trials Enrollment

Insurance Coverage Expanding for Cancer Clinical Trials

A map of the United States highlighting states that have passed legislation or instituted special agreements requiring health plans to pay the cost of routine medical care received by clinical trial participants. Note: The map does not reflect two recent updates, a new law in Iowa and a voluntary insurer agreement in Florida, both of which take effect on July 1. A growing number of states have passed legislation or instituted special agreements requiring health plans to pay the cost of routine medical care received by clinical trial participants. Click on the map above to view information by state. Note: The map does not reflect two recent updates, a new law in Iowa and a voluntary insurer agreement in Florida, both of which take effect on July 1.

The situation, repeated often, goes like this: A patient is diagnosed with cancer. She could choose to receive a standard treatment, but she is also a candidate for a clinical trial. Receiving the standard treatment would mean her insurance company would pay for her care. But were she to enroll in the clinical trial, any costs associated with her treatment would be denied because those costs are considered “experimental”—even though much of the care she might receive would be the same as the standard, with the potential exception of an investigational treatment.

Scenarios like this eventually generated a legislative wave of sorts, with many states adopting laws or other formal agreements requiring coverage for the cost of “routine care” received in clinical trials. The slow, methodical change began in the mid- to late-1990s in places such as Rhode Island, Maryland, and New Jersey. Not long after, Medicare and the U.S. Department of Defense, via its TRICARE health insurance plan, also began to cover such costs. The movement culminated in March with the enactment of the Patient Protection and Affordable Care Act, which requires health insurers to pay for routine costs of care delivered in phase I through phase IV clinical trials, including trials focused on prevention and early diagnosis. (See the sidebar.)

"Routine Costs" Explained

The Patient Protection and Affordable Care Act describes “routine patient costs” in clinical trials that health insurers must cover as “all items and services consistent with the coverage provided in the plan (or coverage) that is typically covered for a qualified individual who is not enrolled in a clinical trial.” This includes items such as hospital visits, imaging or laboratory tests, and medications.

According to the act, it does not include:

  • “The investigational treatment, device, or service itself,” which is typically covered by the trial’s sponsor, such as NCI or a pharmaceutical company
  • “Items and services that are provided solely to satisfy data collection and analysis needs and that are not used in the direct clinical management of the patient”
  • “A service that is clearly inconsistent with widely accepted and established standards of care for a particular diagnosis”

Like many of the insurance reforms in the larger health care reform bill, the new requirement does not take effect until 2014, said Matt Brow, vice president of Government Relations and Public Policy for US Oncology. Once it does take effect, Brow explained, the new law will offer a baseline of coverage for clinical trial participants in all 50 states and the District of Columbia and help plug some gaps in existing state-level laws and agreements. It requires, for example, coverage of routine care costs for clinical trial participants in “self-insured” plans—that is, plans typically offered and run by employers who are paying the full cost of providing the benefits—governed by the federal ERISA law, Brow said. These self-insured plans cannot be regulated by the states.

Progress at the state level has been substantial, if uneven: 33 states and the District of Columbia have a law or agreement that addresses coverage of clinical trials, although the specifics of coverage vary from state to state. (See the sidebar for more information.)

In New Jersey, which has had a clinical trials coverage agreement in place with the state’s largest insurers for more than a decade, the experience has been very positive, said Dr. Susan Goodin, associate director of clinical trials and therapeutics at the Cancer Institute of New Jersey. “We haven’t had a problem with any of the insurers when it comes to covering the standard of care,” she said. “They don’t pay for the research—if we’re doing an extra CT scan or blood draw as part of the study, then that’s on us.”

Attempting to quantify the agreement’s impact on trial accrual has proven difficult, Dr. Goodin continued, but she’s convinced it’s had an effect. “The dialogue [with the insurance companies] was worthwhile and it’s delivered on the promise,” she said.

One of the states to tackle the issue most recently is Nebraska, which in November 2009 reached a voluntary agreement with the 27 health plan members of the Nebraska Insurance Federation to cover the costs of routine care of patients in clinical trials. The charge to get coverage came from Sen. Mike Gloor, who was president and executive officer of St. Francis Medical Center for 28 years prior to his election to the state legislature. During his first term, Sen. Gloor introduced legislation to mandate trial coverage and reached out to the state’s medical and cancer communities to gain their support for the bill.

What Are States Doing?

A state-by-state overview of insurance coverage of clinical trials is available in both the Clinical Trials section of the NCI Web site and at the National Conference of State Legislatures’ Clinical Trials: What Are States Doing?

Regardless of whether a state has a law or agreement that addresses insurer coverage of clinical trials, in cases where resistance from an insurer does arise, Dr. Goodin recommended that a patient’s clinician speak directly with the health plan’s medical director. Those conversations should cover “what are the patient’s treatment options, and whether a clinical trial is the best or most appropriate option for that patient,” she said. “That’s where our success has been.”

“This was one of those nagging frustrations,” Sen. Gloor said of his time at St. Francis. Patients might not enroll in a trial at all because of coverage concerns, he said, or enroll but then drop out because their claims were denied. “Yet once they dropped out, then insurers started picking up the costs anyway,” Sen. Gloor continued. “And the patient lost the benefit of what the clinical trial could offer, and we lost the research data that went along with that.”

Although there are still some issues that need to be clarified, the federal law should address some of the gaps in coverage at the state level, agreed Patrick Taylor, associate general counsel at Children’s Hospital Boston. In a comprehensive analysis of state laws on clinical trials insurance coverage, published in March in the Journal of the National Cancer Institute, Taylor identified a number of potential trouble spots among the patchwork of state laws and agreements, including limitations on trial types that are covered and the adequacy of scientific review for covered trials.

Among the most pressing issues, he explained, was ambiguity about just what “routine care” encompasses, particularly “when you talk about research-related injuries,” Taylor said, which the federal law will cover. Ambiguities in legislation and laws can be unavoidable, he continued, “but it’s essential to cover research-related injuries. That’s a big one; that’s one thing that bankrupts people.”

The effort at the state, and now federal, level has been well worth it, stressed Dr. Kenneth Cowan, director of the University of Nebraska Medical Center’s Eppley Cancer Center. “Cancer patients have so many issues to deal with while they are undergoing treatment,” Dr. Cowan said. “The last thing you want [is for] patients who are enrolling in clinical trials—patients who are trying to help advance science and cancer research—to worry about is whether their care will be paid for.”

Carmen Phillips

Special Issue: Clinical Trials Enrollment

CommunicationsThis is the fourth article in a new series of stories and commentaries related to cancer communications. Look for the symbol on the left in an upcoming issue for the next article in the series.

Talking About Trials: Overcoming Bottlenecks in Clinical Communication

Behind the often-quoted statistic that only about 3 to 5 percent of adult cancer patients participate in clinical trials is the fact that no one knows how many patients are actually offered the opportunity to enroll in one. Eligibility is one factor to consider, as only a minority of adult cancer patients are eligible for any given trial.

Provider recommendation is one of the biggest predictors of use of many services—if your doctor recommends something, you’re likely to do it—but we really don’t know to what extent clinical trials are offered.

—Dr. Neeraj Arora

“But of those who are eligible, how many are asked to participate?” asked Dr. Neeraj Arora, program director in the Outcomes Research Branch of NCI’s Division of Cancer Control and Population Sciences. “Provider recommendation is one of the biggest predictors of use of many services—if your doctor recommends something, you’re likely to do it—but we really don’t know to what extent clinical trials are offered,” he added.

Dr. Arora is currently planning a study as part of the 10,000-patient Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) looking at differences in patients’ care experiences between participants who enrolled in a trial (about 5 percent in CanCORS) and those who did not.

In addition to comparing satisfaction with care between patients treated on and off trials, CanCORS investigators will track how patients heard about clinical trials, whether they discussed the option with their providers, the roles they felt they played in making decisions about participating in a clinical trial, and whether they chose to participate once offered enrollment.

Uncommon Offers

Clues to the likely results from the CanCORS study come from recent work by Dr. Terrance Albrecht and her colleagues at the Barbara Ann Karmanos Cancer Institute in Detroit.

In 2008, the researchers published a study showing that when patients were explicitly offered participation in a clinical trial, 75 percent chose to enroll. However, out of 235 recorded patient–physician interactions reviewed during the study, explicit offers were made only 20 percent of the time. “Patient refusal rates may be less of a problem than low rates of trial offers,” wrote the authors.

Patients who felt that their doctors communicated in a way that built alliances, provided support, and explained the trial in understandable language were more likely to choose to participate in a trial once offered.

“What it really came down to was, in situations where physicians made a clear offer of a trial, when the patients understood that they’d been offered a trial, and when the physicians were engaged in patient-centered communication and provided the necessary information, patients were entering these studies and they were entering them without a lot of second thoughts or serious doubts,” recounted Dr. Albrecht. “What we’re trying to do now is step back and ask why we don’t have more offers.”

A 2007 study from Fox Chase Cancer Center in Philadelphia found that, although most oncologists recognize the importance of clinical trials, some may face their own psychosocial barriers to referring patients. These barriers include concerns about patients’ willingness to be randomly assigned to treatment and physicians’ tendencies to favor clinical trials for patients with late-stage disease or disease that has not responded to standard treatment—patients who may actually be less likely to benefit from an experimental therapy.

But even for oncologists who want to offer trials to their patients, Dr. Albrecht believes that “maybe the system just isn’t set up effectively for doctors to have these conversations.” A large bottleneck is found at the institutional level, since doctors often do not have access to a system that would rapidly and effectively identify which patients are eligible for which trials.

Currently, Dr. Albrecht and her colleagues have a grant from NCI “to go back into the system and increase the number of offers by identifying eligible patients earlier in the process,” she explained. This includes providing tablet computers in clinical team meetings that would let oncology nurses match patients with clinical trials before doctors meet with patients, and better integrating the nursing team into the doctor–patient relationship to serve as an additional resource for information.

But doctors and treatment centers are only one side of the equation. If patients are unfamiliar or uncomfortable with the concept of clinical trials, both informed consent and informed refusal can be impeded.

Changing the Norm

“We believe the discussion about clinical trials should be initiated by the doctor, but if that’s not going to happen—and we can’t always expect for that to happen—then the conversation should be initiated by the patient: Is there a clinical trial for me? Why or why not?” said Margo Michaels, executive director and founder of the Education Network to Advance Cancer Clinical Trials (ENACCT).

ENACCT has developed training programs for communities, health care providers, and researchers with the goal of improving access to cancer clinical trials through education and collaboration with each of these groups. One of their programs trains local community leaders “to spread the word about clinical trials and normalize the concept of clinical trials in a community, which can do two things,” explained Michaels. “It makes it so the first time a patient hears about clinical trials is not at the time of diagnosis, and it can influence a loved one to encourage a patient to ask about clinical trials.”

As of early 2010, ENACCT has trained 85 local community trainers in 6 communities nationwide, who in turn have trained 1,500 of their peers in how to spread the word about the importance of cancer clinical trials. Those 1,500 community leaders have made informal or formal presentations to more than 7,000 community members about why clinical trials are important.

In a test of their Pilot Education Program (PEP) employing this concept, ENACCT used Emerging Med, a commercial clinical trials matching service, to track how many people attending their presentations went on to access additional information about clinical trials. They found that over 3,000 people accessed Emerging Med to learn more about clinical trials after attending community education sessions. In addition, PEP participants boosted the creation of new patient profiles for their geographic areas in the Emerging Med database by approximately 10 percent.

“The peer-to-peer discussions encouraged in our training programs are between equals and can foster familiarity and inquiry about clinical trials,” stated Michaels. “Lack of knowledge and misconceptions about clinical trials play a large part in barriers to participation, and if we can address the knowledge and attitudinal issues, we can help to change the social norms around the importance of clinical trials.”

—Sharon Reynolds

Special Issue: Clinical Trials Enrollment

Taking Action to Diversify Clinical Cancer Research

Many decry the fact that only 3 to 5 percent of adults with cancer in the United States join clinical trials, but a deeper challenge emerges when you put faces to these numbers. Close to 90 percent of those who do enroll in NCI-sponsored studies are white (with Hispanics/Latinos accounting for only 5.6 percent of that amount).

Rural State Networks Link Patients to Clinical Trials

Another example of innovative ways to enhance recruitment in the community setting is the Midwest Cancer Alliance (MCA), a network of 14 institutional partners (universities, health system clinics, hospitals) throughout the state of Kansas and in western Missouri that collaborate with the University of Kansas Cancer Center.

“We’ve been using telemedicine for over 15 years to reach out to the community and provide care close to home,” explained MCA Medical Director Dr. Gary C. Doolittle. “It’s a core part of our mission.”

About 20 percent of Americans live in rural areas, facing common challenges such as less access to care and awareness of clinical trial opportunities. Patients throughout Kansas can enroll in cooperative group and pharmaceutical trials, which are traditionally available only in urban cancer centers, through the MCA. In most cases, they can complete all trial activities without the burden of travel.

“Minority, rural, elderly, and other underserved patient populations bear a heavy burden of cancer disease but remain underrepresented in clinical trials,” says Dr. Jean Ford, from Johns Hopkins Bloomberg School of Public Health. “Not only does this pile one disparity atop another by denying them the benefits of clinical trials as a treatment option, but it potentially compromises the ability to generalize trial results to those groups.” (See the sidebar on rural populations.)

NCI is using several approaches to increase the enrollment of minority and underserved patients in clinical trials. In 2001, the Institute established the Center to Reduce Cancer Health Disparities (CRCHD), in part, to address the problems minorities face in gaining access to cutting-edge cancer care, including the care provided in clinical trials.

“The reasons for cancer health disparities can be complex and unique to specific populations and include behavioral, environmental, and biological factors,” said CRCHD Director Dr. Sanya Springfield at the recent National Minority Quality Forum Seventh Annual Health Disparities Leadership Summit. CRCHD, she added, is funding numerous programs to help train a diverse cadre of investigators to effectively deliver cancer advances, such as those afforded by clinical trials, to diverse and underserved communities at risk for or with poor outcomes.

Dr. Derek Raghavan, director of the Cleveland Clinic Taussig Cancer Institute, agrees that training a diverse clinical trials workforce is critical. He co-authored a recent American Society of Clinical Oncology (ASCO) policy statement on disparities in cancer care. “Improving the proportion of minorities who are recruited into the oncology clinical specialties is a big part of our strategy for increasing minority representation in cancer clinical trials,” he said.

Enrollment at the Community Level

One of the most successful dedicated NCI programs to date for improving minority enrollment in clinical trials is the Division of Cancer Prevention’s Minority-Based Community Clinical Oncology Program (MB-CCOP). Over the past 20 years, the MB-CCOP has worked to help community oncologists who serve large minority populations recruit patients to NCI-sponsored clinical trials at cancer centers, university centers, and community programs. Between 2000 and 2008, MB-CCOP researchers helped recruit nearly 7,000 minority patients in cancer treatment, prevention, and control trials. In fact, nearly two-thirds of all clinical trials participants recruited in the 14 MB-CCOPs are minorities. In 2007, NCI’s Board of Scientific Advisors called on NCI to use the MB-CCOP as a model for its other programs that need greater accrual of minority patients.

Dr. Steven Wolff is director of the MB-CCOP at Meharry Medical College in Nashville, TN, where a shared resource was established at the Nashville General Hospital at Meharry (NGHM) in collaboration with the Vanderbilt-Ingram Cancer Center. This resource is the product of a pilot study funded by CRCHD’s Comprehensive Minority Institution/Cancer Center Partnership program. The program’s goal is to develop and evaluate a model that enhances recruitment and retention of African Americans in national cancer clinical trials.

This program is unique in defining and prioritizing clinical trials that are relevant to the African American patient base at NGHM, Dr. Wolff said. Data on all patients diagnosed with cancer at the hospital are entered into a database, and a nurse navigator is assigned to each patient for follow-up. Procedures are established and customized for each step in the recruitment process, and a research or clinical staff member is assigned to ensure that the step is completed.
After testing and refining the model, 68 percent of those who were eligible to participate in a clinical trial––61 percent of them African American––agreed to take part in one, explained Dr. Wolff. “These accrual rates are more than double those reported in the literature. We attribute our success to a proactive approach, adequate resources, additional time and effort allocated for the informed consent process, decreased logistics, and cultural sensitivity of the research staff.

Community Engagement and Patient Navigators Boost Trial Enrollment

Working closely with the Hispanic/Latino community and assisted by a trained, bilingual patient navigator, investigators from the CRCHD-supported Community Networks Program (CNP), Redes En Acción increased enrollment into pediatric hematology/oncology clinical trials in a South Texas county with increased rates of childhood leukemia.

The Redes En Accion program used a multipronged approach—featuring a Spanish-speaking navigator, community outreach and education, and an enrollment tracking tool—to increase by 48 percent the number of Hispanic/Latino children accrued to local hematology clinical trials. NCI’s Coordinating Center for Clinical Trials helped fund the effort.

“This was a most impressive result,” said CNP Redes En Accion principal investigator, Dr. Amelie Ramirez, “and speaks to the importance of community involvement combined with the promise of navigation to help increase enrollment among some of our most vulnerable populations.”

Beyond Race

Success in tackling the complexities of increasing clinical trials accrual for chronically underserved populations requires a broad array knowledge, abilities, sensitivities, and resources, say experts in the field, because the issues involved transcend race and ethnicity.

“It’s not just race per se,” explained Dr. Ford, of Johns Hopkins, “but rather how sociodemographic factors––such as age, gender, socioeconomic status, income, education, culture, language, and geography, as well as race and ethnicity––influence the process of accrual.”

To look deeper into that process, Dr. Ford’s group conducted a systematic literature review of barriers to recruiting minority and underserved patients to cancer clinical trials. From the 65 studies that met the criteria for review, they culled 150 discrete factors that act as barriers to accrual of underrepresented groups.

Dr. Ford developed a conceptual model that sorts the accrual process into three stages and demonstrates that barriers often differ by stage. Initially, patients must become aware of the role and concept of clinical trials in general. Barriers at this stage include lack of education about clinical trials, lack of physician awareness, and, to a lesser extent, knowledge about the origins of cancer.

Then, they need to learn about relevant opportunities to join specific trials. Barriers at this stage include other illnesses (comorbidities), age, race, inadequate health insurance, lack of provider referral, and socioeconomic status (including income).

Finally, they have to decide whether to enroll. Here barriers include the perceived risks of the treatment and practical concerns such as the time commitment, loss of income, transportation, and loss of control.

Creating Awareness, Building Opportunities

A proven strategy to raise awareness is to focus on the communities where target populations live and work. At Baylor College of Medicine in Houston, Dr. Armin Weinberg leads the Eliminating Disparities in Clinical Trials (EDICT) project. “Addressing any national health concern requires a systematic approach that provides assistance not only directly to individuals, but also promotes change at community, organizational, local, state, and national levels,” Dr. Weinberg said.

After producing policy recommendations to reform the trial enrollment system, Dr. Weinberg and his colleagues took EDICT researchers into eight local communities across the U.S. and engaged local stakeholders in regional community dialogue meetings. These meetings have led to ongoing activity and infrastructure that enhances that community as a context for clinical trials awareness.

Once patients become aware of clinical trials, the next stage is to match patients with clinical trials for which they are eligible. The NCI Community Cancer Centers Program  has developed a process for tracking patients through this process and identifying factors that influence enrollment decisions. Using a Clinical Trials Screening and Accrual Log, hospitals in the network capture race and ethnicity data for all incoming cancer patients, as well as the reasons why patients who are screened for a trial may not join.

“A great example of the value of having strong baseline and tracking data is our new Underserved Patient Navigation Project,” explained Maria Gonzalez, cancer research manager at St. Joseph Hospital in Orange, CA.

At each site, navigators focus on particular cancers (breast, colorectal, etc.) and work closely with those research teams. The navigators disseminate clinical trials information to newly diagnosed patients, assess their needs, and refer appropriate patients for screening.

“Our goal is to have every member of their cancer care team educate the patient about clinical trials,” explained Ms. Gonzalez. “When their treating physicians approach them, most have already developed a good understanding of clinical trials, and that eliminates the ‘fear factor.’

“Our physicians like it because the stage is set for an effective and collaborative meeting over informed consent, reducing the time physicians have to spend on general clinical trials education and emphasizing trial and treatment options,” she said.

Deciding to Enroll

When making their final decision, patients seem to perform a kind of personal calculus of perceived risks and benefits, according to the Hopkins model, including factors such as trust in the trial’s sponsor/investigator, monetary costs, transportation, time, provider-related issues, culture, fear, family considerations/issues, religious/spiritual beliefs, altruism, and stress.

“This is not ‘one size fits all,’” cautioned Dr. Raghavan. “Most factors, both barriers and promoters of accrual, assume a different level of significance depending on which group you are targeting. Perhaps one of the most important issues is for the majority population to care about this issue and to establish real mechanisms to improve access to care and recruitment to trials where appropriate,” he added. 

Drs. Ford, Raghavan, and Wolff co-led a discussion on “The Science of Minority and Underrepresented Accrual” at the recent NCI/ASCO Clinical Trial Accrual Symposium, where conference attendees agreed that targeting specific barriers can improve the situation. “But we have a long way to go,” said Dr. Ford, “and our systematic review of the literature suggests that it is past time for a unified national program that will generate the evidence needed to establish a standard of care that improves population diversity within cancer-related trials.”

—Addison Greenwood

Special Issue: Clinical Trials Enrollment

Overcoming Age Limits in Cancer Clinical Trials

Adolescents and young adults between the ages of 15 and 39 lag behind in clinical trials participation Adolescents and young adults between the ages of 15 and 39 lag behind in clinical trials participation.

More than 90 percent of children younger than 5 who are diagnosed with cancer participate in clinical trials. Perhaps not surprisingly, the greatest improvements in cancer therapeutics in the past 2 decades have been in childhood cancers. Meanwhile, two groups—adolescents and young adults (AYA) between the ages of 15 and 39 and the elderly (see the sidebar)—continue to lag far behind when it comes to clinical trials participation.

AYAs are far less likely to enroll in trials than children and middle-aged adults. The reasons include inadequate health insurance, lack of access and referrals to specialized cancer treatment centers, and the fact that clinicians don’t know of trials for people who fall outside of the age groups for which trials and treatments have traditionally focused. Nonetheless, AYA participation in clinical trials is crucial to the advancement of effective therapies for that age group.

“Twenty-five-year-olds need to participate in clinical trials if we are going to make progress for 25-year-olds,” said Dr. Karen Albritton, director of AYA Oncology at the University of North Texas and Cook Children’s Hospital. 

Understanding Age-specific Tumor Biology

Evidence has shown that, for some cancers, it can be more efficacious to treat AYAs with pediatric treatments instead of adult treatments, said Dr. Nita Seibel of the Clinical Investigations Branch in NCI’s Cancer Therapy Evaluation Program (CTEP).

“We know that for acute lymphoblastic leukemia, if you treat patients ages 16 to 21 with the same treatments as children, the outcome is much better than using treatments for adults,” she said. That might not be the case for all cancers, though. “Particularly when you look at young adults, there are different factors that could influence how their bodies metabolize the chemotherapy that may have an effect on the cancer or cause more side effects,” said Dr. Seibel.

But understanding those biological differences is a bit of a Catch‑22, since that knowledge relies on doing more trials. “The problem is we don’t have a huge repository of tissue samples to detect different gene patterns,” Dr. Seibel explained. “The way to get samples is to collect them when patients enroll in clinical trials. So if they are not enrolled in trials we can’t do the research to find the differences.”

NCI is sponsoring clinical trials specifically for patients aged 21 to 39 to make sure pediatric treatments are not too toxic for them. “Children are treated more aggressively than adults,” Dr. Seibel said. “In pediatric oncology we tend to push harder. We accept some toxicity if it’s for the benefit of a cure. Oftentimes we will accept a lower white blood count or platelet level than in adults, because they will bounce back quickly.” Also, adults may have other health issues that complicate cancer treatment, she added.

Making the Right Referrals

Making sure that AYAs are referred to specialized cancer care facilities following diagnosis is another challenge. “The doctors and nurses at cancer centers are knowledgeable and excited about clinical trials and communicate their importance to patients,” said Dr. Ted Trimble, also with CTEP.

Yet, as Dr. Seibel points out, AYAs are often referred to a community oncologist rather than a comprehensive cancer center, university medical center, or a pediatric center, where they could either enroll directly in trials or be referred to them.

Pediatric cancer centers typically enroll their patients in clinical trials, and the gains made in childhood cancers have mostly taken place at academic centers with government-funded trials. Pharmaceutical companies have generally seen little incentive to invest heavily in drugs for pediatric cancers because the patient pool is very small. And even though the AYA age group represents about six times as many patients as children under the age of 15, there is still little perceived economic incentive for pharmaceutical companies to invest in trials, said Dr. Albritton.

“There’s got to be some sort of carrot, because AYA trials are not going to pay for themselves,” Dr. Albritton said. “Should we have an AYA hospital or incentives like making adult cancer facilities centers of excellence if they have clinical trials for AYAs?” she continued. “Because when you have a population in which cancer is rare, and scatter them across 20 hospitals, no one site is going to open a trial protocol.”

Hope in Health Care Reform

Dr. Seibel is hopeful that health care reform might improve the situation, particularly the provision allowing for some AYAs to be insured under their parents’ coverage until age 26. That is encouraging, but changing the mentality of young people who are not used to seeing a doctor regularly, or when they first notice something wrong, might be challenging, Dr. Seibel cautions.

“Older teens and young adults tend to have sporadic medical care,” she explained. “Part of the problem is that people in this age group think that they will never get sick, and so they don’t want to think about the need for insurance or having to pay for it.”     

Children, on the other hand, have parents who oversee their care. “Once AYAs become more independent, they don’t show the same persistence in maintaining medical care,” Dr. Seibel explained.

And that kind of care is built on trust, which is essential for patients considering clinical trials.

Increasing Interest in Studying AYA Cancers

“By and large, if a patient and his or her family trust the health care team looking after them, then they are willing to consider a clinical trial that is appropriate for them,” Dr. Trimble said.

Doctors, of course, first have to be aware of the trials, and there is evidence of growing interest among researchers and physicians in studying AYA cancers.

According to Dr. Archie Bleyer, medical advisor to CureSearch and LIVESTRONG, there has been “an explosion” of articles on PubMed on AYAs and cancer. In 2009, there were 4,045 peer-reviewed publications on AYA cancer, said Dr. Bleyer, compared with 100 to 200 articles per year a couple of years ago.

“I think the hope is that if everyone is starting to think about studying AYA cancer, we’ll see more clinical trials and translational research,” said Dr. Bleyer. “To me, this is the most impressive news in the past decade.”

NCI’s Cancer Trials Support Unit is also creating a system by which members of adult and pediatric cooperative groups can access each other’s trials.

“Because AYA tumors are often more adult-like, this will be a boon for pediatric oncologists to get adult trials for their older patients,” said Dr. Bleyer. “Conversely, adult cooperative groups with younger patients with pediatric-type cancer can access a pediatric-type trial.”

LIVESTRONG and NCI’s long-standing efforts are a strong support and a response to the “moral imperative” of this issue, said Dr. Albritton: “I feel encouraged by the permanence of this topic. There are a lot of good players at the table.”

—Kristine Crane

The Other End of the Spectrum: Older Adults

Limited clinical trials data is a problem for adults over the age of 65 as well. Like AYAs, older adults are typically treated at community health centers, where doctors might not know about clinical trials, rather than at specialized clinics, where knowledge and enthusiasm for trials tends to be high. Older patients might also be less likely to go for second opinions or get referrals to those clinics.

“An 80‑year‑old might be less encouraged to drive 3 hours to a specialized clinic,” Dr. Trimble said. “The perception is that they’ve already lived a long life and going for the best cancer care is less important than for someone younger.”

Older patients may not receive potentially beneficial treatments because there isn’t enough data showing that such treatments improve survival or out of concern that a treatment may cause more adverse events in older patients. But these patients could also benefit from clinical trials focused on palliative care, said Dr. Martine Extermann, an oncologist with the Senior Adult Oncology Program at Moffitt Cancer Center. “The fact that you cannot do chemo does not mean you cannot do something for patients,” she said. “Supportive care is also care.”

Indeed, a major obstacle to enrolling adults over the age of 65 in trials is that they often have other health problems that make them ineligible to participate.

“They aren’t coming with a clean slate,” said Rose Mary Padberg, a clinical trials nurse specialist at NCI. “By the time you are 65 or older, you usually have something that might cause you to be ineligible for a trial, like hypertension, diabetes, or medications for those conditions.”

According to Dr. Trimble, NCI is working on expanding trial eligibility to include older patients with those kinds of comorbidities or to design new trials that take older patients into account.

“In a lot of cases, we have to establish if a standard chemotherapy dosage can be safely delivered to elderly patients with comorbidities. If we find we can’t deliver the standard dose safely, we have to design separate trials,” he said.

Specifically, trials that test various levels of comorbidities would be helpful, said Dr. Extermann. “Transfer the concept of a phase I/II trial to these patients. Instead of increasing the dose of a drug, increase the level of comorbidity,” she said. “You take sicker and sicker patients and see how much they can tolerate. Then you will have a good estimate of what you can do in a particular subset of patients.”

Prior malignancies are another obstacle to enrollment of older adults, said Dr. Extermann. “Trials shouldn’t exclude prior malignancies if there is no reason not to do it. That’s one in five over the age of 70,” she said.


Special Issue: Clinical Trials Enrollment

Additional Clinical Trials Resources

Cancer Clinical Trials at NIH

The NIH Clinical Center in Bethesda, MD NCI’s Center for Cancer Research conducts hundreds of trials each year at the NIH Clinical Center in Bethesda, MD.

NCI supports cancer clinical trials across the country through its extramural research program. Meanwhile, on NIH’s main campus, the Institute’s intramural researchers in the Center for Cancer Research (CCR) conduct hundreds of trials each year at the NIH Clinical Center in Bethesda, MD, and these trials often differ from those available elsewhere.

While some cancer centers also offer early-stage clinical trials, the difference is that CCR focuses almost exclusively on early-stage trials, said Dr. Bill Dahut, CCR’s clinical director.

NCI’s intramural program is able to pay the transportation costs for patients who are enrolled in Clinical Center trials. This allows CCR to see many more patients with rare cancers, or rare subtypes of common cancers, than other research sites because CCR can fly in patients from around the country to be treated in investigational studies.

One commonly cited barrier to entering clinical trials is the worry among both patients and their physicians of losing control. “An important point about treatment at NCI is that everything we do here for patients is done in close collaboration with their local physicians back home,” Dr. Dahut explained. “Our physicians provide expert clinical care to patients while they are being treated on protocol at NCI, but our physicians can see patients only while they are at the Clinical Center. Thus, continued care by local physicians is incredibly important to allow patients to access standard treatments or other trials not available here. Local physicians must remain closely involved with patients on NCI studies because side effects, from the cancer or the therapy, may occur when the patient is home and far from Bethesda.”

Patients and physicians interested in exploring cancer clinical trials at NIH can visit CCR’s clinical trials Web site. The site includes detailed descriptions of clinical trials currently recruiting patients; information for the general public about clinical trials and participating in trials at NCI; and information for health professionals about referring patients, the Center’s clinical programs and investigators, and ways to keep up to date with CCR research and opportunities.

“We’d really like to encourage physicians to join our mailing list,” said Susan McMullen, patient outreach and recruitment coordinator for CCR’s Office of the Clinical Director.  “One of the barriers to recruiting patients at NIH is that our doctors don’t have a patient base outside of clinical trials to draw from, so we rely on community doctors to refer patients to us.”


Family Cancer Registries

To determine what genetic factors may lead to cancer, researchers rely on those affected by familial cancer to participate in family cancer registries. To determine what genetic factors may lead to cancer, researchers rely on those affected by familial cancer to participate in family cancer registries.

For some families, the tragedy and sorrow of losing a relative to cancer is repeated as family member after family member is diagnosed with the same disease. To determine what genetic factors may be at work and how environmental influences alter those genetic risks, researchers rely on those affected by familial cancer to participate in family cancer registries.

“Our major goal in studying these families is to identify what are called high-risk susceptibility genes,” explained Dr. Peggy Tucker, director of the Human Genetics Program and chief of the Genetic Epidemiology Branch in NCI’s Division of Cancer Epidemiology and Genetics (DCEG). “We then try to understand the function of those genes, how they confer risk, and what other factors within the family modify risk.

“Ultimately, we want to be able to alter the risk of cancer in these families either by identifying susceptibility factors we can modify—for example, avoiding sun exposure in melanoma families—or designing interventions that can affect risk—such as prophylactic oophorectomy for women in families with high risk of both breast and ovarian cancer,” she said.

Family cancer registry studies can also help inform researchers about cancer susceptibility risks in the general population. For example, researchers identified dysplastic nevi as a major risk factor for melanoma by studying families at high risk of melanoma.

Researchers at NCI first began conducting family registry studies in the mid-1960s. These long-term studies follow families through successive generations, and allow researchers to examine the role of inherited high-susceptibility genes and cancer. Today, DCEG researchers are studying families with a number of inherited cancers or cancer-susceptibility syndromes, and researchers in NCI’s Division of Cancer Control and Population Sciences (DCCPS) sponsor the Breast and Colon Cancer Family Registries.

Whereas DCEG’s family registries are conducted at the NIH Clinical Center, the family registries based in DCCPS are found throughout the United States, Australia, and Canada. “Currently, we have about 78,000 men and women from nearly 26,000 families participating in these registries,” said Dr. Sheri Schully, program officer for the DCCPS family registries program. “The main objective of these registries is to identify and characterize cancer susceptibility genes, but the investigators also look at gene–gene and gene–environment interactions as well.”

Although family registry studies do not provide treatment to participating families, investigators often provide test results that can help family members learn which of them may be at higher risk because of certain susceptibility genes, such as mutations in the BRCA1 and BRCA2 genes or those associated with Lynch syndrome, said Dr. Schully.

Additionally, the studies are an opportunity for people who are often desperate for answers to ask questions.

“We like to think it’s a positive experience for them because they have a whole day at NIH to meet with physicians and nurses who know a lot about the disease,” Dr. Tucker explained. “We try to keep them updated with new findings about the diagnosis and management of the cancer that affects their family, and they know they can always come to us for referrals for care of the disorders that we’re studying.”


Learn More About Clinical Trials 

Find a Clinical Trial
Search NCI's list of 8,000+ clinical trials now accepting participants.

Learn About Clinical Trials
Information for all audiences about what clinical trials are, why they are important, and why people choose to take part.

Clinical Trial Results
Browse recent clinical trial results by type of cancer or topic.

Paying for Clinical Trials
Learn about insurance coverage and who is expected to pay for what in a clinical trial.

Patient Safety in Clinical Trials
Learn how the rights and safety of people who take part in clinical trials are protected.

Conducting Clinical Trials
Information and tools for investigators and research teams about conducting clinical trials, including registration and reporting. 

NCI Programs and Initiatives
Information about NCI programs and initiatives that sponsor, conduct, develop, or support clinical trials. Also, information about major NCI-supported clinical trials.

Research About Clinical Trials
Summaries of research studies of the clinical trials process. 

International Collaboration in Clinical Trials
Resources to facilitate international alliances in cancer clinical trials

Cancer Research Highlights

Study Finds No Overall Increased Brain Tumor Risk from Cell Phones

A large international study has found no overall increased risk of two types of brain tumors among people who use mobile phones. The case-control Interphone study analyzed data on cell phone use from more than 5,000 patients in 13 countries who had either glioma or meningioma and from matched comparison groups.

No evidence of overall increased risk was found when the results were analyzed according to increasing numbers of calls, duration of call time, or time since a person started to use cell phones. For a very small proportion of persons who were heavy users, the researchers found an increased risk for glioma, but the results were inconclusive.

“An increased risk of brain cancer is not established from the data from the Interphone study,” said Dr. Christopher Wild, director of the International Agency for Research on Cancer, which coordinated the study. He noted, however, that further research was warranted because of the result involving heavy users and because usage patterns continue to change, particularly among young people.

The findings, published online May 18 in the International Journal of Epidemiology, are consistent with the majority of published reports on cell phones and malignant or benign brain tumors. No previous study, however, has included as many patients with brain and central nervous system tumors who had histories of cell phone use, particularly long-term and heavy users of mobile phones, as this one.

“Interphone will be the most definitive study of cell phones and risk of brain and central nervous system tumors for some time to come,” said Dr. Martha S. Linet, chief of the Radiation Epidemiology Branch in NCI’s Division of Cancer Epidemiology and Genetics. She praised the investigators for going to great lengths to understand and address the methodological challenges in studying cell phone usage in patients with cancer.

The study focused on patients who developed brain tumors between age 30 and 59. A Nordic study is expected to provide some results on children in the next few years, Dr. Linet said. Plans are also under way for a study called MOBI-KIDS, which would evaluate risk from new communications technologies, including cell phones, and other environmental factors in people between age 10 and 24.

Cell phones emit a form of radiation known as radiofrequency energy, but how this affects cancer risk is not clear. Dr. Linet noted that although cell phone usage has been increasing, exposure to radiofrequency energy from cell phones to individuals has declined steadily. This is in part because technology has improved and because there are more cell phone towers, which reduces the amount of radiofrequency energy exposure to the user. The farther a cellular telephone is from the base station antenna, the higher the power level needed to maintain the connection.

Dr. Linet and her colleagues have been monitoring the incidence of brain cancer in the United States during the rise in cell phone usage. “We have not seen an increase in brain tumor incidence that one might expect if there were an increased risk of cancer from cell phone usage,” she said. “This is an important public health message.” (For more information, see NCI’s Cellular Telephone Use and Cancer Risk Fact Sheet.)

Cost of Cancer Care in the U.S. Doubled in the Past 20 Years

The total yearly medical cost of cancer in the United States nearly doubled from $24.7 billion in 1987 to $48.1 billion between 2001 and 2005, according to Dr. Florence Tangka of the CDC and her colleagues in an analysis published online May 10 in Cancer. This increase paralleled the overall increase in medical spending over the past 20 years and remained approximately 5 percent of total medical expenditures over the time period measured.

The researchers used data from 28,639 patients who took part in the National Medical Expenditure Survey in 1987 and data from 135,714 patients who took part in the Medical Expenditure Panel Survey between 2001 and 2005 to produce their cost estimates. All costs were adjusted to 2007 U.S. dollars.

The share of the total costs paid increased for private insurers (from 42 percent to 50 percent), Medicare (from 33 percent to 34 percent), and Medicaid (from 1 percent to 3 percent) but decreased for other public programs (from 7 percent to 5 percent). Out-of-pocket costs decreased from 17 percent to 8 percent.

The delivery of cancer treatment shifted away from the inpatient setting and toward the outpatient setting during the same time period, with 64.4 percent of cancer costs generated by inpatient treatment in 1987 but just 27.5 percent of costs generated by inpatient treatment during 2001 through 2005. Along with increased outpatient costs, spending on cancer-related prescription drugs as a proportion of all cancer-related costs also rose, from 1.8 percent to 6.1 percent.

For private insurance and Medicaid, over 80 percent of the increase in costs could be explained by the increased prevalence of cancer from 1987 to 2005. For Medicare and other public insurance, the cost per person actually decreased; however, the increase in prevalence seen with an aging population “more than made up for a decrease in costs per person,” explained the authors.

Liver Cancer Cases in the U.S. Continued to Rise Through 2006

Rates of the most common form of liver cancer, hepatocellular carcinoma (HCC), continued to rise in the United States, increasing an average of 3.5 percent each year from 2001–2006, according to an analysis published May 7 in the CDC’s Morbidity and Mortality Weekly Report. Close to one-fifth of all cancers worldwide are caused by infectious agents, including chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV).

Using population data from 45 cancer registries (SEER and CDC’s National Program of Cancer Registries) that cover about 90 percent of the U.S. population, CDC researchers identified 48,596 HCC cases during that period and found that incidence rose from 2.7 to 3.2 cases per 100,000.

Racial and ethnic disparities in HCC have been persistent. While Asians/Pacific Islanders had the highest incidence rate (7.8 per 100,000) among subpopulations; that rate did not increase during the study period. Hispanics had the next highest rate (5.7), which increased by only 1.7 percent per year; by contrast, the incidence rate among all non-Hispanics was much lower (2.8) but increased twice as fast, at 3.6 percent per year. African Americans had a slightly lower rate than Hispanics (4.2), but their rate increased the fastest, at 4.8 percent per year. Whites had the next fastest increase, 3.5 percent per year, but the lowest incidence rate (2.6).

“The age and race profile of persons with HCC reflects the demographic characteristics of persons with chronic viral hepatitis,” wrote the authors of an accompanying editorial note. “Development of viral hepatitis services, including screening with care referral for persons chronically infected with HBV or HCV, full implementation of vaccine-based strategies to eliminate hepatitis B, and improved health surveillance are needed to reverse the trend in HCC.”  

Doctors Urged to Monitor Hypertension in Cancer Patients Treated with Anti-VEGF Therapies

Patients with cancer who will be treated with certain anti-angiogenesis agents should have their blood pressure monitored carefully and managed prior to and during treatment, according to recommendations published in the May 5 Journal of the National Cancer Institute. The recommendations were developed by an expert panel convened by the Investigational Drug Steering Committee in NCI’s Division of Cancer Treatment and Diagnosis.

The report covers the use of agents that target the vascular endothelial growth factor (VEGF) signaling pathway, a key regulator of blood vessel development to tumors. FDA-approved agents in this drug class include bevacizumab (Avastin), pazopanib (Votrient), sunitinib (Sutent), and sorafenib (Nexavar). All of these VEGF signaling pathway inhibitors have been associated with cardiovascular side effects, particularly hypertension, explained panel chair Dr. Michael Maitland of the University of Chicago, and his colleagues. As a result, they wrote, “Oncologists and cardiovascular medicine specialists have increasingly recognized that the prevention and management of these toxic effects is important for these potentially life-sustaining anticancer agents to benefit the greatest possible number of patients.”

The recommendations were developed based on the available published data on hypertension in patients treated with these agents, as well as the panel’s experience with the use and development of these drugs and current standards for managing hypertension. Based on its review, the panel advised that patients who will receive VEGF signaling pathway inhibitors undergo a formal risk assessment for cardiovascular complications from treatment; that efforts to control hypertension should begin prior to starting treatment with any of these therapies; and that active monitoring and management of hypertension continue after treatment has begun.

When necessary (e.g., because of hypertension-related symptoms or difficulty controlling blood pressure), the panel recommended that treatment with VEGF signaling pathway inhibitors can be temporarily discontinued or the dose reduced to bring hypertension under control. Nevertheless, they advised, efforts “should be made to maintain the patient at the highest tolerable dose” of these inhibitors.

Legislative Update

Cures Acceleration Network Featured at Senate Appropriations Subcommittee Hearing

Translating the promise of basic science discovery into tangible benefits for patients was the central theme of the May 5 hearing held by the Senate Appropriations Subcommittee on Labor, Health and Human Services, Education, and Related Agencies to discuss the President’s fiscal year 2011 budget request for NIH. NIH Director Dr. Francis Collins, building on his previous testimony before the House Appropriations Subcommittee in April, described recent scientific advances and identified opportunities for progress. “If our nation can be bold enough to act upon these many unprecedented opportunities, we’ll be amazed at what tomorrow will bring and how swiftly we can turn discovery into health,” he said.

Dr. Collins and several subcommittee members highlighted a new program concept, the Cures Acceleration Network (CAN), authorized in the Patient Protection and Affordable Care Act (PL 111-148). Dr. Collins praised the new flexible research authorities afforded by the CAN to develop partnerships designed to take basic science discovery through development and production and into clinical practice. These partnerships “go beyond traditional grants, contracts, and cooperative agreements, to manage projects in very forward-thinking ways,” he explained. Establishing the CAN program hinges on an actual appropriation of funds specifically designated for this purpose, as stipulated in the legislation, and the subcommittee engaged in a lively debate about how the program could be adequately funded in an environment of severely limited resources and competing priorities.

In response to the subcommittee’s concerns about the lack of progress against pancreatic cancer, Dr. Collins described how the CAN could prove useful. Dr. Collins was confident that the work of The Cancer Genome Atlas will “give us a comprehensive ability both to do a better job of early diagnosis but most importantly to identify new therapeutic magic bullets.” The CAN, he said, could assist in speeding development from target identification to therapeutic intervention.

The subcommittee was also concerned about the recent Institute of Medicine (IOM) report describing shortcomings in the cancer clinical trials program. Dr. Collins reassured the subcommittee that NCI, which requested the IOM analysis, is taking appropriate action to improve the entire clinical trials process. Update

Recovery Act Web Site Highlights NCI Clinical Proteomic Technologies for Cancer Initiative

Screenshot of American Recovery and Reinvestment Act at NCI Web page

NCI's American Recovery and Reinvestment Act (ARRA) Web site features new content that highlights the NCI Clinical Proteomic Technologies for Cancer (CPTC) program and describes how Recovery Act funding is helping support an initiative to measure the 250,000 to 1,000,000 proteins in the human body. This pilot project is studying the feasibility and scalability of emerging technologies to accurately measure such large numbers of proteins. By studying the human proteome, researchers hope to learn more about how cancer originates and devise new and better methods for diagnosis, treatment, and prevention.

Learn more about CPTC and other important initiatives here.


PLCO EEMS Seeks Applicants

Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial data and biospecimens are available to qualified researchers through a peer-review process. The Etiologic and Early Marker Studies (EEMS) program accepts proposals for access to PLCO biospecimens twice a year, in June/July and December/January.

By collecting biologic materials and risk-factor information from trial participants before the diagnosis of disease, EEMS—a component of the PLCO—provides a resource for cancer researchers who are focused on cancer etiology and early markers. Etiologic studies investigate the environmental, biochemical, and genetic risk factors for cancer. Early detection studies aim to develop reproducible, reliable biomarkers of early disease.

Proposals will be accepted for the EEMS summer review cycle starting June 1, 2010. Applications will be accepted until July 15, 2010, at 5:00 p.m. EDT. Details of the review process and application materials are available at Questions may be directed to or 240-314-5896.

Enter the Celebrating Smokefree Voices Video Contest

Screenshot of Web page

Smokefree Women is launching a video contest, Celebrating Smokefree Voices, to capture the variety of quitting experiences and reasons for quitting smoking among women and their friends and families across the United States. These videos are an opportunity to share reasons why being smokefree is important to you.

There are two categories for video submissions:

  1. Why I Am a Smokefree Woman: Create a video that tells others why you stay smokefree. What are your reasons and motivations? What does it mean to you to be a smokefree woman?
  2. Why I Want YOU to be Smokefree: Is there a woman in your life that you care about who smokes? Create a video and let them know why you want them to enjoy a smokefree life and the freedom from cigarettes.

Three winners named in each category will receive prizes of up to $2,000.

All video entries must be submitted by June 4, along with the required video entry form. Contest winners will be announced on July 2, right before Independence Day, to celebrate independence from smoking.

Visit to watch the call-for-submissions video and to find contest instructions.

Meet NCI Experts at ASCO

Learn about NCI’s programs and Web sites by visiting booth #2033 in the exhibit hall during the 2010 American Society of Clinical Oncology annual meeting. NCI experts will be available to talk about a wide range of topics. See the schedule below.

Saturday, June 5

11:00 a.m.AccrualNet
Ellen Richmond and Linda Parreco
12:00 p.m.Funding for Biomarker, Imaging, & QOL Studies Associated with NCI’s Clinical Trials
Geoffrey Seidel
1:00 p.m.NCI Online Course: Including Clinical Trials in Your Practice
Rose Mary Padberg
2:00 p.m.Using TNF-alpha Antagonists to Treat Primary Tumors and Tumor Metastases
Charles Rainwater
3:00 p.m.AccrualNet
Holly Massett and Rose Mary Padberg
4:00 p.m.Cancer Training Branch
Susan Lim

Sunday, June 6

10:00 a.m.NCI Online Course: Including Clinical Trials in Your Practice
Linda Parreco
11:00 a.m.NCI’s Office of Cancer Complementary and Alternative Medicine
Farrah Zia
12:00 p.m.Overview of Specialized Programs of Research Excellence (SPOREs)
Rajeev Agarwal
1:00 p.m.NCI SBIR Funding for Small Startup Businesses to Bring Science to the Market
Gregory Evans
2:00 p.m.Using TNF-alpha Antagonists to Treat Primary Tumor and Tumor Metastases
Charles Rainwater
3:00 p.m.Funding for Biomarker, Imaging, & QOL Studies Associated with NCI’s Clinical Trials
Geoffrey Seidel
4:00 p.m.Funding Opportunities to Promote Workplace Diversity
John O. Ojeifo

Monday, June 7

9:00 a.m.Translational Research Program (SPOREs)
Ivan Ding
11:00 a.m.Funding for Biomarker, Imaging, & QOL Studies Associated with NCI’s Clinical Trials
Geoffrey Seidel

Abstracts Accepted for the Molecular Markers in Cancer Meeting

The ASCO-NCI-EORTC Annual Meeting on Molecular Markers in Cancer will be held October 18–20 in Hollywood, FL. Participants will discuss the rapidly advancing field of cancer markers and practical applications for biomarker research and treatment. Abstract submissions on the following topics are being accepted through June 22:

  • Clinical applications of biomarkers
  • Application of new and established technologies and platforms
  • Immune system and immunotherapeutic markers
  • DNA repair and apoptosis
  • Circulating tumor cells and cancer stem cells
  • Cell signaling pathways
  • Genetics, genomics, epigenetics, gene expression

President’s Cancer Panel Issues Report on Environmental Cancer Risks

Cover of Reducing Environmental Cancer Risk

On May 6, the President’s Cancer Panel issued a report titled “Reducing Environmental Cancer Risk: What We Can Do Now.” The report summarizes the Panel’s findings from four meetings convened between September 2008 and January 2009 to assess the state of environmental cancer research, policy, and programs addressing known and potential effects of environmental exposures on cancer. The report’s conclusions are based on the information gathered at those four meetings, as well as testimony received from 45 invited experts from academia, government, industry, environmental and cancer advocacy communities, and the public. The Panel’s recommendations delineate specific actions that governments; industry; the research, health care, and advocacy communities; and individuals can take to reduce cancer risk related to environmental contaminants, excess radiation, and other harmful exposures.

This latest report from the Panel is one of a series. Two previous reports addressed promoting healthy lifestyles and maximizing the nation’s investment in cancer research.

Updated NCI Spanish-language Booklet on Breast Cancer

NCI has released a newly revised Spanish-language booklet for recently diagnosed breast cancer patients titled Lo que usted necesita saber sobre el cancer de seno (What You Need To Know About Breast Cancer). This booklet tells about diagnosis, treatment choices by stage, breast reconstruction, and follow-up care. It also describes how to take part in research studies and includes lists of questions to ask a physician.

This booklet and the other eight Spanish booklets in the series are available at en español. Order copies of these and other NCI education materials from the NCI Publications Locator Web site or by calling 1-800-4-CANCER.