National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
May 3, 2011 • Volume 8 / Number 9

NEWS

FDA Approves Abiraterone for Advanced Prostate Cancer

A ball-and-stick model of the abiraterone molecule For the second time in a year, the Food and Drug Administration (FDA) has approved a new treatment for men with advanced prostate cancer who, until recently, have had few effective treatment options.

Last Thursday, the agency approved abiraterone (Zytiga) for the treatment of men with metastatic castration-resistant prostate cancer (meaning the disease progresses despite low levels of tumor-fueling hormones) who are no longer responding to the chemotherapy drug docetaxel. Read more > >


COMMENTARY

A Conversation with Drs. Maureen Hatch and Kiyohiko Mabuchi on the 25th Anniversary of the Chernobyl Nuclear Disaster

The researchers from NCI's Radiation Epidemiology Branch discuss lessons learned from the Chernobyl accident and research on the health consequences of the accident. Read more > >

A MESSAGE TO READERS

NCI's Fiscal Picture and Grant Support for FY2011

Last week, NCI Director Dr. Harold Varmus e-mailed staff regarding NCI's budget and the challenges ahead for the cancer research community. View the full text of the email  online.

  

IN DEPTH

UPDATES

  • Legislative Update

    • State Cancer Legislative Database Update Now Available
  • Notes

    • NCI's Gottesman and Fraumeni Receive Prestigious Honors
    • NCI Experts Advise U.S. Embassy Staff in Japan during Fukushima Nuclear Crisis
    • NCI's Clinical Assay Development Program Seeks Project Applications
    • President's Cancer Panel Report Focuses on Need for Better Understanding of Diverse Populations
    • Second Telephone Workshop for Cancer Survivors Addresses Weight Changes
    • Registry of Measures for Childhood Obesity Research Available

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.

For more information about cancer, call 1-800-4-CANCER or visit http://www.cancer.gov.

NCI Cancer Bulletin staff can be reached at ncicancerbulletin@mail.nih.gov.

Featured Article

FDA Approves Abiraterone for Advanced Prostate Cancer

A ball-and-stick model of the abiraterone molecule On April 28, the FDA approved abiraterone (Zytiga), pictured above, for the treatment of men with metastatic castration-resistant prostate cancer who are no longer responding to the chemotherapy drug docetaxel.

For the second time in a year, the Food and Drug Administration (FDA) has approved a new treatment for men with advanced prostate cancer who, until recently, have had few effective treatment options.

Last Thursday, the agency approved abiraterone (Zytiga) for the treatment of men with metastatic castration-resistant prostate cancer (meaning the disease progresses despite low levels of tumor-fueling hormones) that are no longer responding to the chemotherapy drug docetaxel. Last spring, the agency approved cabazitaxel (Jevtana) for the same indication. In both cases, the approvals were based on findings from large phase III trials in which the drugs improved patient survival.

The availability of these two new drugs—as well as the immunotherapy sipuleucel-T (Provenge), which the FDA approved last April as an alternative to docetaxel for some men with metastatic castration-resistant prostate cancer—has altered the treatment landscape for advanced prostate cancer, several researchers said.

With a number of other experimental drugs in clinical trials also showing promise for the treatment of metastatic prostate cancer, it’s almost “an embarrassment of riches” at the moment, said Dr. Ian Thompson, of the University of Texas Health Science Center at San Antonio.

But although the survival improvements produced by abiraterone and cabazitaxel are meaningful, he cautioned, the benefits are still modest: both drugs improve patients’ median overall survival by approximately 2 to 4 months.

In addition, the availability of multiple treatment options creates new—albeit welcome—problems, as researchers and clinicians must now try to make difficult decisions about which drugs to use in which patients and when. Some of these decisions, however, involve so-called “off-label” uses of the available therapies.

Androgens Are Still Important

Abiraterone’s approval was based on findings from a clinical trial, funded by the drug’s manufacturer, Cougar Biotechnology, in which nearly 1,200 patients were randomly assigned to abiraterone in combination with the steroid prednisone or to prednisone plus placebo. The median overall survival was 14.8 months in patients who received abiraterone and prednisone and 10.9 months in those who received prednisone alone, researchers reported last December at a major European cancer conference. Patients treated with abiraterone experienced few serious side effects. (Findings from the trial that led to cabazitaxel approval were reported in March 2010).

Abiraterone and cabazitaxel haven’t been compared in a head-to-head trial, but abiraterone has fewer serious side effects and can be taken orally, which may make it the preferred first option for these patients, said Dr. William Dahut of NCI’s Center for Cancer Research.

“The ease of administration [of abiraterone] and the favorable side-effect profile will obviously play a role in which treatment clinicians and patients choose,” agreed Dr. Maha Hussain of the University of Michigan Comprehensive Cancer Center.

Patients who have already been treated with the drug ketoconazole may be an exception. (Although not approved by the FDA for use in men with advanced prostate cancer, ketoconazole has proven beneficial for some patients.) “Patients with prior exposure to ketoconazole probably don’t respond as well to abiraterone” as those who haven’t received it, Dr. Dahut explained.

Whereas cabazitaxel is a next-generation drug in the class of chemotherapy agents called taxanes, abiraterone is the first in an approaching wave of new agents for prostate cancer that, directly or indirectly, target testosterone—a wave that represents a “paradigm shift” in the treatment of this disease, according to Dr. Dahut. (See the box at the bottom of the page.) Abiraterone works by inhibiting an enzyme, CYP17, that plays a central role in allowing the body to produce testosterone from cholesterol.

Drug-induced castration with luteinizing hormone-releasing hormone agonists—which rob prostate tumor cells of the testosterone they need to grow—has been a standard and successful treatment for prostate cancer for several decades. But in many patients the disease eventually progresses despite very low levels of available testosterone.

“Fifteen years ago, it was largely believed that once a patient's disease progressed on hormone therapy, he was hormone refractory and there was really no point going on to second- and third-line hormonal therapies,” Dr. Dahut said. But tumor cells, studies have shown, adapt to a low-androgen environment, in part by increasing the expression of the androgen receptors on their surfaces. So, while the overall amount of testosterone in the body may be very low, it’s still being produced, and tumor cells develop the ability to take in as much as they can get.

Abiraterone’s efficacy, he added, signals “the importance of targeting testosterone” even in patients in whom the hormone “is at castrate levels.”

Which Drugs, Combinations, or Sequences?

The availability of several new treatment options for advanced prostate cancer has created a situation in which patients and their doctors may need to make difficult clinical decisions when there isn’t necessarily sufficient clinical evidence. For example, some doctors will likely want to use abiraterone in patients with advanced disease who are no longer responding to standard hormonal therapies but who have not yet been treated with docetaxel.

Patients are likely to have responses to abiraterone at this point in their disease, Drs. Dahut and Hussain agreed, although, Dr. Dahut cautioned, there is no evidence yet that this treatment approach will improve survival. And, Dr. Hussain added, insurance coverage of this off-label indication is unlikely at this time. A phase III trial testing this approach is under way.

If the FDA eventually approves abiraterone for use in patients with castration-resistant disease who have not yet been treated with docetaxel, there will also be questions about whether abiraterone or sipuleucel-T should be used first.

More research is needed to determine the best sequence of therapies, or which combination of therapies might be more effective, Dr. Thompson said. The goal is to “conduct adaptive trials that use multiple agents that are most likely to benefit the individual patient,” he added.

Efforts in this area need to proceed with serious deliberation and care, Dr. Hussain stressed, particularly when it comes to testing combinations of drugs. “Smart, rational approaches supported by scientific mechanistic data to justify testing these agents in combination are needed,” she said, “not just because they’re available and we can do it.”

Carmen Phillips

Doubling Down on Testosterone

In addition to abiraterone, two other drugs are in phase III clinical trials in men with castration-resistant prostate cancer that is no longer responding to docetaxel: TAK-700 and MDV3100.

In addition to testosterone, abiraterone affects production of other hormones that can lead to side effects such as hypertension; steroids are used to protect against or mitigate such side effects. Steroids can have their own long-term side effects, though, so the need to combine abiraterone with steroids could limit use of abiraterone in men with earlier-stage disease and longer life expectancies, Dr. Thompson noted.

Like abiraterone, TAK-700 also targets CYP17, but TAK-700 may be more selective in suppressing androgen production and does not appear to have a dose-response effect, Dr. Hussain explained. As a result, the drug can potentially be used at doses that won’t require concomitant steroid supplementation.

MDV3100 works differently, disrupting tumor cells’ ability to use testosterone. It does this in part by clogging up androgen receptors. Because of its mechanism of action, MDV3100 does not have to be used in combination with steroids.

Regardless of each drug’s strengths and weaknesses, the availability of efficacious second- and third-generation androgen-targeted agents represents “major progress,” Dr. Hussain said. “Each new agent appears to be better than the prior ones. This is great for patients.”

Cancer Research Highlights

Tool Weighs Benefits, Risks of Raloxifene or Tamoxifen to Prevent Breast Cancer

Researchers have developed a benefit-risk index to help guide decisions on whether postmenopausal women at increased risk of developing breast cancer should take raloxifene or tamoxifen to reduce that risk. Although studies have shown that these drugs can reduce breast cancer risk, the drugs can also cause adverse side effects, so women and their physicians must decide whether the potential benefits of one or the other drug outweigh the risks in each patient’s particular situation.

The results of the benefit-risk analysis, reported online May 2 in the Journal of Clinical Oncology, showed that the risks and benefits of taking raloxifene or tamoxifen depend on a woman’s age, race/ethnicity, projected 5-year breast cancer risk, and whether she has had a hysterectomy. Overall, the analysis showed that raloxifene is better than tamoxifen for reducing breast cancer risk in women with a uterus. For women who have had a hysterectomy, the benefit-risk profiles for raloxifene and tamoxifen are similar.

Dr. Worta McCaskill-Stevens of NCI’s Division of Cancer Prevention, Dr. Andrew Freedman of NCI’s Division of Cancer Control and Population Sciences, and their colleagues used data from the Women’s Health Initiative, SEER, and two large clinical trials—the Breast Cancer Prevention Trial (BCPT) and the Study of Tamoxifen and Raloxifene (STAR) trial—that evaluated the ability of tamoxifen and raloxifene to prevent invasive breast cancer (IBC) in women at high risk for the disease. They considered non-breast cancer health outcomes, including bone fractures, blood clots, stroke, and endometrial cancer, rates of which were potentially increased or decreased by raloxifene or tamoxifen.

The researchers then assigned a weight to each possible health outcome, and to IBC and in situ breast cancer, and calculated the probability that a woman with various risk factors would have each outcome in 5 years with and without raloxifene or tamoxifen. They used these calculations to create color-coded tables for each drug that show, for each age group and 5-year projected risk of IBC, whether there is strong or moderate evidence that the benefits outweigh the risks or that the risks outweigh the benefits. The researchers created separate tables for white non-Hispanic, black, and Hispanic postmenopausal women 50 years of age or older, with and without a uterus.

“By using NCI’s Breast Cancer Risk Assessment Tool (BRCAT) to estimate the projected 5-year risk of IBC, a health care provider can obtain a benefit-risk index from the corresponding table entries,” the study authors wrote. “By combining this information with information on clinical features and personal preferences, the health care provider and patient can make an informed decision.”

In an accompanying editorial, Drs. Eitan Amir and Pamela J. Goodwin, of the University of Toronto, described some limitations of the analysis but noted: “[This new tool is] the most comprehensive attempt to date to individualize chemoprevention by enabling clinicians to select tamoxifen or raloxifene for patients on the basis of a number of key patient attributes. This is a clear step forward for breast cancer prevention and may ultimately lead to improvement in uptake of chemoprevention strategies.”

Intensity-Modulated Radiation Therapy Use for Breast Cancer Influenced by Reimbursement

A new study finds that intensity-modulated radiation therapy (IMRT) use for breast cancer is five times higher in regions where Medicare covers the technique than in regions where Medicare does not cover the technique. The study, published online April 29 in the Journal of the National Cancer Institute, also found that IMRT use was 36 percent higher for women treated at private radiation clinics than in hospital-based outpatient clinics and that regional differences in reimbursement policies appear to strongly influence the use of IMRT. 

Because other 3-dimensional radiation planning methods that are less expensive than IMRT but likely as effective are available, the study authors suggest that Medicare reimbursement options for breast radiation therapy be expanded to allow the use of these less-expensive radiation planning methods.

Between 2001 and 2005, the number of Medicare claims for IMRT for breast cancer rose from 0.9 percent to 11.2 percent of overall radiation therapy claims. The increased use of IMRT contributed to a 26 percent increase in the cost of radiation therapy for breast cancer during the time period studied, reported researchers led by Dr. Benjamin D. Smith of the University of Texas M. D. Anderson Cancer Center.

Dr. Smith and his colleagues used the linked SEER-Medicare database to collect data on 26,163 women 66 years of age and older treated with surgery and adjuvant radiation therapy for nonmetastatic breast cancer.
 
The mean cost of radiation therapy given in the first year after diagnosis was $7,170 for women who did not receive IMRT and $15,230 for women who received IMRT. Costs related to radiation therapy accounted for 33 percent of total medical care costs for women who did not receive IMRT and 52 percent of costs for those who received IMRT.

Because the characteristics of patients’ tumors were not strongly associated with whether IMRT was used, whereas allowed reimbursement was associated with IMRT use, the study results “would appear to confirm the suspicion…that medical decision making is too heavily influenced by reimbursement rather than medical necessity,” wrote Drs. Lisa A. Kachnic and Simon N. Powell of the Boston University Medical Center in an accompanying editorial

Whether IMRT for breast cancer is more effective at targeting cancer cells or reducing side effects than less-expensive 3-dimensional radiation techniques is still unclear. Clinical trials are needed to understand which women with breast cancer benefit the most from IMRT, they added.

Whole-Genome Sequencing Improves Cancer Diagnoses

Although whole-genome sequencing is not yet ready for routine clinical use, two studies show how the approach could improve the diagnosis and, potentially, the treatment of cancer. The reports, in the April 20 Journal of the American Medical Association, describe how researchers at Washington University School of Medicine in St. Louis and their colleagues used whole-genome sequencing to investigate the cases of two patients.

The first study focused on a 42-year-old woman who died from leukemia that was probably related to previous treatment for breast and ovarian cancers. The woman did not have a known family history of cancer, and tests for mutations in the breast cancer-associated genes BRCA1 and BRCA2 were negative. But a comparison of the genomes of her cancer cells and normal cells revealed a novel mutation in the TP53 gene that altered the function of the encoded protein. TP53 gene mutations have been implicated in a number of cancers, including some early-onset breast and ovarian cancers, as well as Li-Fraumeni syndrome.

The TP53 mutation does not appear to have been inherited from one of the patient’s parents. But because the mutation was seen in both normal and cancer cells, it had to have occurred very early in the patient’s life, possibly at conception. Thus, the mutation could have been present in her germline DNA and been passed on to her children, the researchers noted.

As specified by the study protocol, the researchers contacted the woman’s primary care physician, who then discussed the issue with the patient’s family members and encouraged them to seek genetic counseling. “Even though the patient died, her contribution to this study yielded new knowledge that might one day save the lives of her children,” study co-author Dan Koboldt of the Genome Institute at Washington University wrote in a post about the studies on his blog, MassGenomics.

The second study involved a 39-year-old woman with a form of acute myeloid leukemia (AML). A comparison of DNA from her tumor and normal cells revealed a fusion of two genes in her blood cells that was not detected through routine cytogenetic testing. The presence of this gene fusion is associated with good outcomes after chemotherapy. Consequently, the patient’s doctors recommended chemotherapy rather than stem cell transplantation, the treatment that had been indicated by the standard diagnostic testing results.

At the time of publication, the woman had been in remission for 15 months. The sequencing, analysis, and validation of the fusion gene were completed in just 7 weeks, which was quick enough that doctors could use the information to choose the most effective treatment for the patient, the researchers noted.

“These cases of personalized genomic medicine are just some of the first examples of what will likely be commonplace in the near future,” wrote the authors of an accompanying editorial.

“Clearly, the technology will no longer be the major impediment to widespread clinical use of these tools, and the main challenges will soon move to the clinical implementation and interpretation of genomic data,” the authors added.

Researchers Identify Proteins that Help Hepatitis C Virus Enter Liver Cells

Scientists have identified two proteins found on the surface of liver cells that help the hepatitis C virus (HCV) enter the cells, the first step in a viral infection that causes liver disease and increases the risk of liver cancer. Both proteins are a type of molecule called receptor tyrosine kinases. Anticancer drugs called tyrosine kinase inhibitors (TKIs) blocked the action of the identified proteins and reduced HCV infection in laboratory models of the disease, reported researchers led by Drs. Joachim Lupberger and Mirjam B. Zeisel from the University of Strasbourg in France. The results were published online April 24 in Nature Medicine.

To identify liver cell proteins that the virus exploits to gain entry, the researchers first used small inhibitory RNAs to block several kinase proteins one by one. They found that silencing the expression of two such proteins—epidermal growth factor receptor (EGFR) and ephrin receptor A2 (EphA2)—stopped HCV particles from entering the cells.

Two approved TKIs, erlotinib and dasatinib, inhibit EGFR and EphA2, respectively. When the researchers treated liver cells with the drugs, HCV entry was impaired. Two other TKIs that inhibit EGFR, gefitinib and lapatinib, had similar effects. In experiments testing cell-to-cell transmission of HCV, erlotinib and dasatinib stopped the virus from spreading from infected cells for up to 2 weeks (the length of the experiment).

Further studies of the cell-signaling networks controlled by EGFR and EphA2 indicated that these proteins do not appear to be necessary for HCV to bind to cells. Instead, they seem to be involved in the virus’ ability to enter the cell. When tested in a mouse model of HCV infection, erlotinib substantially reduced the level of viral infection and was well tolerated.

Chronic hepatitis infection is one of the most common causes of liver cancer, and current treatments are inadequate. Although these findings are preliminary, the authors suggest that targeting receptor tyrosine kinases may provide a new way to prevent HCV infection after exposure and to treat existing HCV infections.

 

A Conversation With

A Conversation with Drs. Maureen Hatch and Kiyohiko Mabuchi on the 25th Anniversary of the Chernobyl Nuclear Disaster

Drs. Maureen Hatch and Kiyohiko Mabuchi Drs. Maureen Hatch and Kiyohiko Mabuchi

April 26 marked the 25th anniversary of the accident at the Chernobyl nuclear power plant in northern Ukraine. In addition to causing 28 near-term deaths due to acute radiation poisoning, the accident exposed 5 million people in Belarus, Russia, and Ukraine to radioactive fallout, mainly iodine-131 and cesium-137. This exposure has led to extensive epidemiology research over the past 25 years by the governments of Ukraine, Belarus, and the United States and their research partners. At NCI, this epidemiology research is led by scientists in the Radiation Epidemiology Branch (REB) of the Division of Cancer Epidemiology and Genetics (DCEG). Dr. Maureen Hatch, former head and current member of the Chernobyl Research Unit (CRU) at DCEG, and Dr. Kiyohiko Mabuchi, deputy branch chief of REB, head of the CRU, and senior scientist, discuss the lessons learned from the Chernobyl accident and summarize some of the ongoing research on the health consequences of the accident.

What lessons have been learned from the Chernobyl accident, in terms of the health consequences?

Dr. Hatch: Prior to the accident, iodine-131 (I-131), the major component of fallout from Chernobyl and a radioisotope that concentrates in the thyroid gland, was believed to have low or no malignant potential. The NCI-supported cohort studies of exposed young people in Ukraine and Belarus [who underwent screening examinations for thyroid cancer every 2 years]  have provided solid evidence that I-131 exposure in childhood and adolescence increases the risk of thyroid cancer, confirming the observations based on post-accident case-control and ecologic studies by others. 

The magnitude of the increased risks observed in both countries is consistent with that following external radiation in childhood, as is the fact that thyroid cancer risk in Ukraine remains significantly elevated decades after exposure. In addition, a separate study of nearly 2,600 people who were exposed in utero to I-131 fallout from the Chernobyl accident found a high radiation-related risk of thyroid cancer.

Dr. Mabuchi: One of the important questions in radiation research is whether cancer risk from chronic exposure is lower than the risk from acute exposures. In a study of more than 110,000 male cleanup workers in Ukraine who sustained repeated exposures to external radiation, NCI investigators observed a radiation-related risk of leukemia comparable to risks experienced by Japanese atomic bomb survivors with acute exposure. 

In addition to the risk for leukemia overall, the NCI study results, in agreement with those from studies of Chernobyl cleanup workers in Belarus, Russia, and the Baltic countries, found a radiation effect on chronic lymphocytic leukemia, a type of leukemia that had not been linked to radiation exposure before the Chernobyl accident.

What lessons have been learned about larger public health considerations, such as possible preventive measures and how best to communicate health concerns to the public?

Dr. Hatch: It’s clearly a challenge to balance the need to communicate protective measures effectively while avoiding widespread anxiety. Residents from the most contaminated area surrounding the Chernobyl plant were evacuated fairly expeditiously. However, the distribution of potassium iodide (KI) to decrease thyroid uptake of I-131 was neither entirely timely nor systematic, in part out of concern that doing so would alarm the population.

In the area surrounding Chernobyl, most of the I-131 exposure to the thyroid among the public resulted from consumption of contaminated cow’s milk. The NCI studies and other epidemiologic studies have clearly indicated the importance of considering the pasture-cow-milk pathway in countermeasures following nuclear accidents. In theory, some thyroid cancer cases might have been averted if the government had issued a broad public health warning and/or banned certain contaminated foods. It is clearly important that governments experiencing disasters of any kind find a way to convey reliable, realistic, and understandable information about evolving events and known health risks without being either alarmist or obfuscating.

The findings of adverse effects on those exposed to Chernobyl fallout prenatally and at young ages also have clinical implications—for example, not using I-131 to treat thyroid disease in pregnant women or young children. The medical community and the public need to be educated accordingly.

What research is the staff in REB doing with regard to the consequences of the Chernobyl accident?

Dr. Mabuchi: At NCI, we are conducting two genetic studies using specimens stored at the Chernobyl Tissue Bank from Ukrainian and Russian subjects who were exposed to fallout from Chernobyl. (Read the story on the Chernobyl Tissue Bank in this issue.) We are also continuing to monitor cancer incidence in members of the Ukrainian and Belarusian thyroid cohorts and among cleanup workers via linkage with the National Cancer Registries in both countries. In addition, we are conducting an additional follow-up examination of Ukrainian subjects who had thyroid nodules identified during one of the earlier biennial thyroid screening cycles.

What questions still remain regarding the health effects of the Chernobyl accident?

Dr. Mabuchi: Questions that remain include the duration and magnitude of post-Chernobyl thyroid cancer risk among exposed young people. We will need continued follow-up in one form or another to learn how long the excess risk will continue. In addition, the thyroid cancer risks to those exposed as fetuses or young adults remain uncertain.

Studies by other investigators of cleanup workers in Ukraine and Russia have reported increases in risk for solid tumors. However, the reported increases have not been convincingly linked to radiation from the accident. There have also been reports of increases in noncancer outcomes, such as cataracts, cardiovascular disease, and mental health problems. 

Future epidemiologic studies of the risk of these diseases among Chernobyl cleanup workers will be challenging because of the need to take into account the effects of behavioral and other factors. The indications are that any excess cases attributable to Chernobyl exposure are likely to be small relative to cases arising from non-radiation-related causes.

What have researchers and public health officials learned from the Chernobyl experience that is or will be applicable to the evolving situation at the Fukushima Daiichi nuclear reactor in Japan?

Dr. Hatch: One critical lesson learned is that major accidents like Chernobyl and Fukushima, affecting large segments of the population, need to be followed up by carefully designed epidemiologic studies assessing the nature and magnitude of adverse health effects. To conduct such studies, exposed people must be clearly defined at the earliest possible time, and efforts must be made to estimate accurately the extent of exposure and disease using all available sources of data and fieldwork approaches. 

Dose measurement and reconstruction, as well as case ascertainment, should be rigorous and standardized. Such studies require timely planning and multidisciplinary, often multinational, collaboration.

The need to take prompt countermeasures to minimize the absorption of radioiodines by the thyroid to prevent thyroid cancer is another lesson learned, along with the importance of emergency preparedness and clear, complete, and trustworthy communication concerning the extent of exposure and potential health risks.

Elia Ben-Ari

Special Report

Chernobyl Tissue Bank Provides a Unique Resource to Researchers

Damaged nuclear reactor at Chernobyl Twenty-five years after the Chernobyl nuclear reactor disaster, tissue samples from individuals affected by the fallout offer important research opportunities.

Twelve years after the 1986 Chernobyl nuclear reactor disaster, a tissue bank was established to coordinate access to high-quality tissue samples for research purposes and to integrate data on radiation-related thyroid cancer. Today, the Chernobyl Tissue Bank (CTB) serves as a unique resource for research on the biology of thyroid cancer.

Since 1998, the CTB has been collecting tissue and blood samples from patients who were exposed to radioactive iodine, or radioiodine, from Chernobyl fallout and who later developed thyroid tumors. The samples are a limited resource. To extend the research that can be conducted with a single specimen, approved researchers receive nucleic acid extracted from the thyroid tissue, instead of the tissue itself. Paraffin-embedded sections of tissue from loco-regional metastases and tissue microarrays are also available.

“The CTB represents a good model for global collaboration to advance the understanding of the biology of a particular cancer,” said Dr. Rihab Yassin, NCI’s representative to the CTB international steering committee, which is responsible for the strategic direction of the project. She also serves as the NCI program official for the grant that provides support for CTB research.

A Global Research Effort

The original idea behind the CTB was to collect tissue samples from people with Chernobyl-associated thyroid tumors and to make those samples available to researchers around the globe, explained Dr. Geraldine Thomas, director of the CTB and professor of Molecular Pathology at Imperial College, London. That vision is now a reality. A new online portal, launched April 26 to coincide with the 25th anniversary of the accident, makes it easier to search for samples and corresponding data.

The CTB is the first international effort to house specimens from tumors that are caused by a known environmental source to further global research collaboration. The tissue banks are located in two of the countries greatly affected by the disaster—Ukraine and Russia—and the database is maintained at the Coordinating Centre at Imperial College, London. The CTB is supported financially by the European Commission, NCI, and the Sasakawa Memorial Health Foundation of Japan.

To date, the CTB contains thousands of samples from 2,840 patients, who fall into one of three categories: individuals who were 19 years old or younger at the time of the accident; those who were born between April 27 and December 31, 1986, when they were likely exposed to radioiodine in utero; and those born in the affected region after January 1, 1987, when the radioisotope iodine-131 (I-131) had already dissipated in the environment.

Decades Later, Better Experiments

Since its inception, the CTB has provided material for research projects in Japan, Europe, and the United States. Investigators must submit an application detailing their research project in order to gain access to the samples. The application is subject to review and scoring by an international External Review Panel (ERP) to ensure the scientific quality of these research projects. 

One of those studies, the NCI-sponsored Ukraine-American Cohort study, is examining the relationship between radiation dose and the molecular biology of the tumors. The European Commission sponsored a study to identify pathways that are important in radiation-associated thyroid cancer.

“We’ve now reached a place,” Dr. Thomas said, “that will add much more valuable data to what we know.” The population that was exposed to the radioiodine is just now reaching the age (25 to 44) that is associated with an increase in incidence of sporadic thyroid cancer. “We don’t really know what’s going to happen with these individuals,” she said. “Have we already seen a peak in radiation-induced thyroid cancer? Or will there be even more cases as the exposed population approaches the usual peak for incidence of this disease?”

Additionally, researchers are observing people from nearby geographic areas who were not exposed to radioiodine and who have now reached the age at which thyroid cancer may develop spontaneously. “We had to wait 20 years to do the proper experiment,” Dr. Thomas said, “which is taking age-matched cohorts and comparing sporadic thyroid cancer to radiation-induced thyroid cancer.”

Several reports have suggested that there may be small differences, such as chromosomal amplification in a proportion of radiation-associated cancers that aren’t seen in the non-radiation-associated cancers. However, these studies need to be validated, Dr. Thomas stressed, which is why the CTB’s work is important. Other findings from research projects using CTB tissue samples suggest that thyroid cancers that arise in younger patients are molecularly different from adult-onset thyroid cancer.

From Research to Possible Treatments

The next phase for the CTB is to make bioinformatics tools available to researchers so that they can continue to analyze data, Dr. Thomas said. She also hopes that the data collected from the CTB will eventually help advance patient care.

“We’d like to be able to use the primary tumors to tell which tumors will recur, so that we can treat those patients differently,” she said. “Nobody has ever systematically collected this number of tumors for research purposes, so the CTB will help answer a lot of questions.”

And the incidence of sporadic thyroid cancer appears to be increasing in the United States, Dr. Yassin noted, although the reasons for this increase are being debated. “The CTB samples are important to help understand these cancers as well.”

Dr. Thomas agreed, adding that the incidence rate of thyroid cancer is climbing globally. She hopes that what is learned from the Chernobyl-related thyroid cancers will boost general knowledge of the disease. “The most important thing is, can we do something to help patients in the future?” she asked.

The research done with CTB material could also be relevant to the recent events in Japan, said Dr. Thomas. “My message has been, don’t panic. We’ve done research on Chernobyl, and we know it’s children and pregnant women who need to be most careful. The Japanese government communicated that message to the Japanese population very effectively.”

Sarah Curry

Spotlight

Use and Acceptance of HPV Vaccine Still a Work in Progress

A bellwether moment in the history of cancer prevention came in 2006 when the Food and Drug Administration (FDA) approved the first vaccine to prevent cervical cancer. The vaccine, Gardasil, protects against the two primary cancer-causing, or oncogenic, types of the human papillomavirus (HPV)—HPV-16 and HPV-18. These types are responsible for more than 70 percent of cervical cancer cases worldwide. In 2009, the FDA approved a second HPV vaccine, Cervarix, which also targets HPV-16 and HPV-18.

Health professional delivering a vaccine injection to a young girl Gardasil and Cervarix, vaccines that protect against the two primary cancer-causing types of the human papillomavirus (HPV), entail a three-shot regimen, with each dose delivered several months apart.

But what has transpired since these two vaccines received regulatory blessing in the United States has reaffirmed something that cancer and public health researchers have appreciated for some time: The translation of basic research to the clinic doesn’t end with FDA approval of a new drug or treatment. In many respects, FDA approval is just a beginning.

In March 2007, the CDC’s Advisory Committee on Immunization Practices (ACIP) gave its strongest recommendation for HPV vaccination for females ages 9 to 26, which is the FDA-approved indication for Gardasil. Cervarix is approved for females ages 10 to 25. Both vaccines entail a three-shot regimen, with the doses delivered several months apart. According to the most recent data, only 44 percent of adolescent girls 13 to 17 years of age have received at least one dose of the vaccine. Completion rates for the three-shot regimen are substantially lower, with only 27 percent of adolescent girls receiving all three doses.

“Uptake is low because of problems with policy, problems with clinical encounters, and problems with parents’ decisions,” said Dr. Noel Brewer of the University of North Carolina Gillings School of Global Public Health. These obstacles are by no means insurmountable, but addressing each obstacle will take time, patience, and research, say investigators working in this area. And a good bit of that research can be grouped into two categories: missed opportunities and teachable moments.

HPV Vaccines for Boys

Gardasil has also been approved by the FDA for use in boys. The initial approval in boys, in 2009, was for the prevention of genital warts because Gardasil, unlike Cervarix, also protects against two other HPV types—HPV-6 and HPV-11—that are the primary cause of genital warts. 

But, in December 2010, the approval was expanded to include the prevention of anal cancer, another disease associated with HPV-16 and HPV-18 infection. Because the approval for boys is so recent, this article focuses only on the uptake of the HPV vaccines by females.

No vaccine has an uptake rate of 100 percent, although when vaccines are mandated, such as those required for school attendance, vaccination rates can reach 80 to 90 percent. Although there has been a flurry of legislative activity at the state level since Gardasil was approved in 2006, only Virginia and Washington, DC, require HPV vaccination for school entry, and Virginia’s law includes a provision that allows parents to opt out of the requirement.

Based on surveys that Dr. Brewer and his colleagues have conducted, concerns that HPV vaccination will encourage sexual activity seem to have had little to do with the lagging vaccination rates. Nor, he continued, has uptake of the vaccines been substantially affected by the antivaccine movement that was spurred by fears raised about the now-discredited links between autism and childhood vaccines.

In general, concerns about safety and other issues with vaccines “are not specific to the HPV vaccine,” said Dr. Gregory Zimet of the Indiana University Melvin and Bren Simon Cancer Center. “There is a general vaccine hesitancy that affects a lot of parents.”

The Power of Physician Recommendations

Factors affecting vaccination rates have “definitely been a mixed bag,” agreed Veronica Chollette, who oversees a portfolio of HPV vaccine-related research in NCI’s Division of Cancer Control and Population Sciences. Cultural issues, lack of awareness, and, initially, reimbursement issues that limited the amount of vaccine physicians were willing to keep in stock have all played a role, she noted.

Physician encounters have also had an effect in an entirely different way. In a study published last year, less than 60 percent of pediatricians reported that they strongly recommended HPV vaccination for their 11- to 12-year-old patients. Another study of women ages 19 to 26 showed that, among women whose doctors did not recommend HPV vaccination, only 5 percent were vaccinated. Among those who did receive a recommendation, 85 percent were vaccinated.

“Pediatricians and family physicians are missing a lot of opportunities when patients come in for office visits,” said Dr. Brewer. Part of the problem, he added, is a systemic issue: health care providers are not flagging the charts of patients who are eligible for the vaccines or using reminder systems in electronic medical records, for example.

Interactions with the health care system drop precipitously once kids reach adolescence, he continued. “So it’s a big deal to miss those chances.”

Sociocultural factors are also important to consider. A study conducted in Appalachia, for example, found that conservative religious beliefs and a mistrust of outside influences played a prominent role in the vaccines’ acceptability. Meanwhile, studies of college-age women have shown that, even when receipt of the initial HPV vaccine dose was similar among white and black women, completion rates for all three doses were substantially lower among black women.

The disparity is noteworthy, Chollette stressed, because black women and Hispanic women have significantly higher cervical cancer incidence and death rates than white women.

In some cases insurance status can affect vaccine uptake and adherence. But, because federal and state-level programs, such as the Vaccines for Children program, make the vaccines available for free or for a minimal charge to low-income children, it may not contribute as much to the disparities in vaccination rates, said Dr. Ruth Carlos of the University of Michigan Medical Center. In fact, a higher percentage of 13- to 17-year-old girls from families below the poverty line have received at least one dose of the vaccine compared with girls from families above the poverty line (52 percent versus 42 percent). Also, a provision in the federal health care reform law requires private insurers to cover all ACIP-recommended vaccines with no co-pay requirements.

It’s a complex problem, acknowledged Dr. Zimet. For example, based on studies he has done involving the hepatitis B vaccine, he explained, “practical obstacles, like transportation to the clinic and how many children the mom is taking care of at home” can have an impact, particularly on adherence to the three-shot regimen.

A variety of approaches are being tested to increase vaccination rates, many of which are focused on moments or interactions that can influence awareness and decision making. Drs. Zimet and Brewer lead initiatives in their respective states that are part of the national Cervical Cancer-Free America campaign. In North Carolina, Dr. Brewer said, they are focusing their efforts on school-located health centers, where many children already receive other vaccines.

Other studies and programs are testing whether social media and text messaging can be used as educational platforms and reminder systems for adolescents and women.

A Mother’s Attitude Is Key

For younger girls, the available data strongly indicate that a single factor heavily influences whether they get vaccinated: their mother. “The gateway to adoption of the vaccine[s] is through the parents,” Chollette stressed. In particular, she continued, mothers are the key. “The mother’s values play a prominent role in whether girls go to the doctor and get all three doses according to schedule.”

Dr. Carlos and her colleagues are attempting to use cancer screening appointments as “teachable moments” for mothers of adolescent girls. In two separate studies, women undergoing breast and cervical cancer screenings who have adolescent daughters will receive tailored information about cervical cancer and the HPV vaccines. The studies will test different means of providing the information, including using a Web-based platform, and vaccination rates will be tracked via electronic medical records.

“From a public health perspective, it makes perfect sense to target mothers who come in for cancer screening,” Dr. Carlos said. Women undergoing their own cancer screenings “may be more receptive to acting on educational information about HPV prevention,” she continued. “Part of what this study is doing is encouraging this receptivity after being screened, and using that to encourage them to get their daughters vaccinated. The message is: ‘You’ve done something to protect yourself against cancer, so why not protect your daughter against HPV?’”

Carmen Phillips

 

A Closer Look

Design Dilemma: The Debate over Using Placebos in Cancer Clinical Trials

Pills spilling out of bottle Many new molecularly targeted anticancer agents are taken in pill form. Because these agents may halt or slow tumor growth without causing tumor shrinkage, some cancer researchers argue that placebo-controlled trials are needed to show that tumor stability is a treatment effect.

Ask a clinical researcher in almost any field except cancer for the “gold standard” of assessing the effectiveness of a new therapeutic drug and you will probably get the same answer: a randomized double-blinded placebo-controlled trial, in which neither patients nor their doctors know who is receiving the active treatment and who is receiving the inert substance. 

By contrast, cancer clinical trials—for practical and ethical reasons—rarely are blinded or include placebo control groups. Most conventional chemotherapy agents have distinctive, often severe side effects that make blinded trials impractical. Moreover, many patients and researchers assert that in trials for a life-threatening condition such as cancer, placebos are inappropriate and that all participants should receive active treatment.

Indeed, placebos are rarely used in most early-phase trials, which are not usually randomized studies and are often first-in-human studies of new agents. Mary Schwartz of Newport News, VA, was diagnosed with stage IV adrenal cancer in 2004 at the age of 35. She has now been cancer free for 6 years after being treated with an investigational chemotherapy regimen in a phase II clinical trial at the NIH Clinical Center. Would she have considered enrolling in a randomized placebo-controlled trial had one been available and offered to her? Absolutely not, she said. 

“Because of the rarity of my cancer and the almost certainty of fatality, I would not have chosen to participate if there had been a possibility of getting a placebo,” she said. “I would have wanted to know I was getting the investigational treatment.”

When Placebos Make Sense

Now, however, with the emergence of novel molecularly targeted anticancer agents, some cancer researchers have begun to challenge tradition and are conducting placebo-controlled trials of new anticancer agents. They cite two major reasons why they believe such trials are now feasible and, in some cases, necessary.

First, unlike conventional chemotherapy drugs—which are frequently given intravenously and produce obvious side effects such as nausea, vomiting, and hair loss—many molecularly targeted agents are taken in pill form and cause side effects, like fatigue or headaches, that can be hard to distinguish from effects of the cancer itself or from other medical problems unrelated to the cancer.

And second, because many molecularly targeted agents halt or slow tumor growth without causing tumor shrinkage (the conventional measure of an anticancer drug’s effectiveness), placebo-controlled trials are needed to show that tumor stability is a treatment effect and not the tumor’s natural behavior.

Scientifically Feasible

“When a tumor shrinks, that’s presumed to be a direct treatment effect. It’s exceedingly rare for cancer to shrink spontaneously,” said Dr. Richard L. Schilsky of the University of Chicago, past chair of the Cancer and Leukemia Group B, an NCI-supported Clinical Trials Cooperative Group, and senior author of a Journal of Clinical Oncology paper arguing that placebo-controlled cancer clinical trials are scientifically feasible, are ethically justifiable in certain circumstances, and may be necessary or desirable to meet regulatory standards for drug approval.

But “if lack of cancer growth is your endpoint, it’s more complicated,” Dr. Schilsky continued. “I have patients I’ve been observing for years, with no treatment, who have had no tumor growth.”

Dr. Schilsky and his co-authors stress that the use of placebos in cancer clinical trials is ethically acceptable only when there is no effective therapy for the patients’ stage of disease. The authors also stress that patients randomly assigned to a placebo must receive best supportive care; that is, treatment of pain and other symptoms but no anticancer treatment.

Randomized trials comparing active treatment to placebo plus best supportive care led to the Food and Drug Administration’s (FDA) approval for the molecularly targeted anticancer agents sorafenib for advanced kidney cancer and sunitinib for gastrointestinal stromal tumors. Placebo use is also ethically acceptable in trials with an “add-on” design, in which patients randomly assigned to one arm receive standard therapy plus the investigational drug while those in the other arm receive standard therapy plus a placebo. Trials of this design led the FDA to approve erlotinib for advanced pancreatic cancer and for advanced non-small cell lung cancer.

A novel type of trial design minimizes placebo use but can still reveal whether stable disease is a treatment effect or natural tumor behavior. All patients in the trial initially receive the investigational drug. Those whose tumors shrink remain on the drug, whereas those who experience severe side effects or whose tumors grow are withdrawn from the trial. Patients with stable tumors are then assigned in a randomized double-blinded fashion to either continue active treatment or receive a placebo. Those whose cancers progress are unblinded and, if they were receiving the placebo, are put back on active treatment.

Trials designed in this way demonstrated the activity of sorafenib in advanced kidney cancer and also showed that the drug carboxyaminoimidazole was no more effective than a placebo in treating that disease.

A Check against Bias

The use of a placebo control group can also serve as a check against the subtle bias that may be introduced when physicians know that one group of patients in a trial is not receiving active treatment, noted Dr. Jeffrey Abrams, associate director of NCI’s Cancer Therapy Evaluation Program.

“You may unintentionally get more scans or x-rays of patients in the observation arm of the study, and so you may find disease progression sooner than you might find it among patients in the investigational arm,” Dr. Abrams said. “When there is no known effective treatment for the patient’s stage of disease, the use of a placebo as an alternative to observation only in the control arm can help control for this type of bias because both investigator and patient are blinded to treatment assignment.”

The use of a placebo can also help researchers better understand a new drug’s side effects, continued Dr. Abrams. “Without a placebo, there’s a tendency to attribute every reported side effect to the study drug. But in a placebo-controlled study, you may find that patients on the placebo arm report some of the same side effects. So you get a more accurate picture of the true side effects of the investigational drug.”

Dr. Richard Pazdur, director of FDA’s Office of Oncology Drug Products, said he sympathizes with the view that patients who are facing a life-threatening condition like cancer want to have active treatment. “There is almost always an alternative to using a placebo in a cancer clinical trial,” he said. “What you have to ask is: What will the use of a placebo achieve that could not be achieved with another trial design?”

Eleanor Mayfield

Rationale for Using an Intravenous Placebo

The use of intravenous (IV) placebos in cancer clinical trials is especially controversial because it requires patients to undergo an invasive procedure, the placing of an IV line, that is of no benefit to them.

Investigators with the Gynecologic Oncology Group, an NCI-supported cooperative group, were well aware of this concern when they designed GOG 0218, a phase III trial that evaluated the benefit of adding bevacizumab to standard chemotherapy for advanced ovarian cancer. Bevacizumab is given as an IV infusion.

“We knew from previous studies that physicians tend to monitor trial participants more intensively when the patients are being observed but not receiving active treatment,” explained principal investigator Dr. Robert A. Burger of Fox Chase Cancer Center. More frequent monitoring of these patients could lead to earlier identification of disease progression, which could bias the study results in favor of the group receiving bevacizumab.

To guard against this potential bias, the investigators designed a three-arm trial to include administration of an IV placebo. Patients were randomly assigned to receive standard chemotherapy plus either IV bevacizumab or IV placebo, followed by continued therapy with either IV bevacizumab or IV placebo.

“We anticipated that we would have difficulty accruing patients,” said Dr. Burger. “Before the trial was launched we organized an educational symposium for investigators and trial support staff. One of the issues we covered was the rationale for designing the trial in this way. We also reached out to ovarian cancer advocacy groups.”

The investigators carefully explained the trial design to prospective patients during the informed consent process, Dr. Burger continued. “We felt it was important to be transparent to ensure that patients understood that it was a research study, our reasons for using a placebo, and that it would make no difference to their treatment if they chose not to participate.”

The trial achieved its accrual goals, enrolling 1,873 patients in four countries. In results reported at the 2010 American Society of Clinical Oncology annual meeting, disease progression was delayed by a median of 4 months and reduced by 28 percent overall in patients who received standard chemotherapy plus bevacizumab followed by continued treatment with IV bevacizumab compared with patients who received standard chemotherapy plus IV placebo followed by continued treatment with IV placebo.

Featured Clinical Trial

Testing Dose-Dense Paclitaxel for Ovarian and Related Cancers

Name of the Trial
Phase III Randomized Study of Two Different Dose Schedules of Paclitaxel in Combination with Carboplatin with versus without Concurrent and Consolidation Bevacizumab in Patients With Stage III-IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer (GOG-0262). See the protocol summary.

Dr. John Chan Dr. John Chan

Principal Investigator 
Dr. John Chan, Gynecologic Oncology Group

Why This Trial Is Important  
Women with ovarian epithelial, fallopian tube, or primary peritoneal cancer usually undergo surgery to determine the extent of their disease (primary staging) and to remove as much cancerous tissue as possible (cytoreduction). Advanced cancer (stage III or IV) is typically treated with combination chemotherapy using a taxane drug, such as paclitaxel, and a platinum-based drug, carboplatin. Emerging evidence suggests the addition of drugs that target angiogenesis may improve outcomes for these patients.

Although standard combination chemotherapy is frequently successful in bringing about a remission, the disease in many women eventually develops resistance to this therapy and subsequently recurs. Doctors are eager to identify new approaches to overcome drug resistance and prolong disease remission and patient survival.

Paclitaxel kills cancer cells by blocking cell division (mitosis), which induces cell death, or apoptosis. Animal studies have shown, however, that the apoptosis induced by paclitaxel begins to subside about 4 days after the drug is administered, suggesting that more frequent and lower-dose administration may improve efficacy. Consequently, doctors have developed a new “dose-dense” administration schedule, with lower doses of paclitaxel given every week instead of a single higher dose given every 3 weeks.

Clinical trials in patients with breast cancer have shown that a dose-dense regimen of paclitaxel produces better responses and stabilization of disease than the standard every 3-weeks dosing schedule. In early clinical trials in patients with advanced ovarian cancer, objective responses were obtained in women whose disease was resistant to standard therapy. To explore this finding further, the U.S. Gynecologic Oncology Group (GOG) conducted a phase II study of weekly paclitaxel in women with advanced platinum- and paclitaxel-resistant ovarian cancer and showed a benefit even in this treatment-resistant group of women.

Further bolstering evidence of dose-dense paclitaxel’s promise in ovarian cancer, the Japanese GOG conducted a phase III randomized clinical trial and showed that women receiving dose-dense therapy experienced statistically significantly longer progression-free survival and were more likely to be alive after 2 years.

In GOG-0262, women with stage III or IV ovarian epithelial, fallopian tube, or primary peritoneal cancer will be randomly assigned to receive either standard or dose-dense paclitaxel in addition to standard carboplatin (given once every 3 weeks). Prior to randomization, women enrolled in the study may elect whether to receive the antiangiogenesis drug bevacizumab during and after chemotherapy. Doctors will monitor women in the trial for progression-free and overall survival, side effects, and quality of life.

“We know that some drugs given at different schedules can produce additional benefits. With dose-dense paclitaxel, not only is there a direct cytotoxic effect, but we can potentially see antiangiogenic benefits above and beyond the effects of paclitaxel given at the standard schedule,” explained Dr. Chan.

“Data from phase II studies show that dose-dense paclitaxel has activity in highly resistant ovarian cancer,” said Dr. Chan. “And the Japanese study has produced promising data, but there are differences in the prevailing ovarian cancer cell types, and possibly the genomic and toxicity profiles, of ovarian cancer in Asian compared with Western women. As such, these results need to be confirmed in other ethnicities before the dose-dense regimen can be considered the new standard of care.”

For More Information
See the lists of entry criteria and trial contact information or call the NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The toll-free call is confidential.

An archive of "Featured Clinical Trial" columns is available at http://www.cancer.gov/clinicaltrials/featured.

Legislative Update

State Cancer Legislative Database Update Now Available

Cover of SCLD Update

NCI’s State Cancer Legislative Database (SCLD) Web site has been updated with the latest edition of the SCLD Update.

This issue features a summary and matrix of all enacted state legislation and resolutions reported in the SCLD Update during 2010, as well as a table focusing on state legislative activity related to tobacco settlements. The issue also contains an overview of all new cancer-related measures enacted by state legislatures during the fourth quarter of last year.

Notes

NCI's Gottesman and Fraumeni Receive Prestigious Honors

Drs. Susan Gottesman and Joseph F. Fraumeni, Jr. Drs. Susan Gottesman and
Joseph F. Fraumeni, Jr.

Dr. Susan Gottesman, co-chief of the Laboratory of Molecular Biology in NCI’s Center for Cancer Research, is the 2011 winner of the Abbott‐ASM Lifetime Achievement Award, the American Society for Microbiology’s (ASM) premier award for sustained contributions to the microbiological sciences.

Dr. Gottesman’s recent work on small regulatory RNAs and energy-dependent proteolysis has uncovered two important regulatory mechanisms in cells, answering basic questions about cancer and leading to further areas of research. Dr. Gottesman has been elected to the American Academy of Microbiology, the National Academy of Sciences, and the American Academy of Arts and Sciences. 

ASM is the world’s oldest and largest life sciences organization and has more than 40,000 members worldwide. The Abbott‐ASM Lifetime Achievement Award will be presented during the ASM’s general meeting, May 21–24, 2011, in New Orleans, LA.

Dr. Joseph F. Fraumeni, Jr., director of NCI’s Division of Cancer Epidemiology and Genetics, was recently elected to the American Academy of Arts and Sciences. He was recognized for research that helped to uncover the genetic and environmental determinants of cancer, leading to new avenues for prevention. Dr. Fraumeni has been elected to the National Academy of Sciences, the Institute of Medicine, and the Association of American Physicians.
 
Dr. Fraumeni is one of 212 new members selected to join the academy, a leading center for independent policy research. Members contribute to studies of science and technology policy, global security, and other academic areas.

The current membership includes more than 250 Nobel laureates and more than 60 Pulitzer Prize winners. The new members, including Dr. Fraumeni, will be inducted at a ceremony on October 1 at the academy’s headquarters in Cambridge, MA.

NCI Experts Advise U.S. Embassy Staff in Japan during Fukushima Nuclear Crisis

Drs. Steve Simon and C. Norman Coleman Drs. Steve Simon and C. Norman Coleman

At the request of U.S. Ambassador to Japan John Roos, U.S. Department of Health and Human Services Assistant Secretary for Preparedness and Response Dr. Nicole Lurie deployed a team of subject matter experts to advise U.S. embassy staff in Tokyo on ways to protect Americans in Japan during the Fukushima Daiichi nuclear power plant crisis. Dr. C. Norman Coleman, associate director of NCI’s Radiation Research Program, and Dr. Steve Simon, a health physicist in NCI’s Radiation Epidemiology Branch, were part of the team that also included Jana Telfer and Tom Bowman of the CDC and Capt. Michael Noska of the FDA.

The team spent several weeks in Japan consulting on a range of issues related to radiation exposure and the health of Americans in Japan during the Fukushima nuclear crisis. They advised on what constituted safe levels of radioactivity in food and drinking water, the necessity of and conditions for evacuation around the power plant and the conditions for return, and the circumstances under which Americans should take potassium iodide to prevent radiation exposure to the thyroid. The team developed communication materials for the embassy to use to convey health and safety information to American citizens living in Japan.

“We evaluated measurements of radiation levels in Tokyo and interpreted them into potential health risks,” explained Dr. Simon. “With that information, American citizens could determine whether they wished to leave or stay, and whether or not to take precautions. That’s a very individual decision,” he explained.

The team also worked with colleagues in the Japanese government to develop research questions that will need to be addressed, added Dr. Coleman.

Videos of the expert team members speaking on topics related to the Fukushima nuclear crisis are currently available on the Web site of the U.S. embassy in Tokyo.

NCI's Clinical Assay Development Program Seeks Project Applications

The NCI Clinical Assay Development Program (CADP), a new initiative for researchers in academia, government, and industry, is requesting project applications from investigators seeking clinical assay validation resources. These resources are designed to assist with the development of assays that may predict therapy response or prognostic behavior of a diagnosed cancer, primarily for use in clinical trials. Approved projects will be provided access to NCI’s assay development and validation resources, including project management support.

Applicants should define the intended clinical use for the assay for which support is requested. Assays submitted for validation should have been tested on human tissue. As part of the application, investigators are required to provide basic assay protocol(s). Proposals will be reviewed for scientific merit, feasibility, and clinical importance.

Please note that this call for applications is not a solicitation for biomarker discovery and is not a grants program. Learn more about CADP or submit an application online. The 2011 deadlines for CADP applications are June 15 and October 15.

President's Cancer Panel Report Focuses on Need for Better Understanding of Diverse Populations

Cover of the President’s Cancer Panel 2009–2010 Annual Report

Last week, the President’s Cancer Panel released its 2009–2010 annual report, America’s Demographic and Cultural Transformation: Implications for Cancer. The report identifies an urgent need to expand research and improve understanding of the factors that influence cancer risk and outcomes among diverse populations. In the report, the panel also calls for higher standards of cultural competence among health care professionals to better address cultural and language barriers that can have a negative impact on the quality of patient care.

The President’s Cancer Panel was established by the National Cancer Act of 1971. It is an independent entity that is charged with monitoring the National Cancer Program and reporting annually to the president on any barriers to the execution of the program. 

Panel members are appointed by the president. Current members include Dr. LaSalle D. Leffall, Jr., of Howard University, and Dr. Margaret L. Kripke, of the University of Texas M. D. Anderson Cancer Center. Although the panel receives logistical and staff support from NCI, it does not conduct scientific research and its conclusions and recommendations should not be inferred as policy or perspectives of NCI.

Second Telephone Workshop for Cancer Survivors Addresses Weight Changes

The second of four telephone workshops in NCI’s annual, “Living With, Through, and Beyond Cancer,” series will be held May 10. Part II of the series is titled “Weight Changes after Cancer Treatments: Why Is It Happening and What Can I Do About It?

This free series offers cancer survivors, their families and friends, and health care professionals practical information to help them cope with concerns and issues that arise after treatment ends. The workshops are presented by CancerCare, in collaboration with NCI, LIVESTRONG, the American Cancer Society, the Intercultural Cancer Council, Living Beyond Breast Cancer, and the National Coalition for Cancer Survivorship.

Speakers for the May 10 workshop include Dr. Anna L. Schwartz of the University of Washington and St. John’s Medical Center, Dr. Jennifer A. Ligibel of Harvard Medical School and the Dana-Farber Cancer Institute, and Dr. Cheryl L. Rock of the University of California, San Diego.

The workshops are free, and no telephone charges apply. To register, visit the CancerCare Web site. All workshops will take place on Tuesdays from 1:30 p.m. to 2:30 p.m. EDT. The two remaining workshops will be held on the following dates:

If you missed Part I of the series, “Chemobrain: The Impact of Cancer Treatments on Memory, Thinking, and Attention,” a recording is available online via podcast.

Registry of Measures for Childhood Obesity Research Available

The National Collaborative on Childhood Obesity Research (NCCOR)—a collaboration among CDC, the Robert Wood Johnson Foundation, NIH, and the U.S. Department of Agriculture—has launched a free, searchable online registry of measures and resources to use in childhood obesity research.  NCCOR’s Measures Registry is an interactive Web tool developed to facilitate access to available measures, describe the operational characteristics of the measures and populations in which the measures have been used, help identify gaps in measures, and encourage the development of new measures. 

The registry includes almost 750 measures on individual dietary behavior, food environment, individual physical activity, and physical activity environment. These measures come from questionnaires, instruments, diaries, logs, electronic devices, direct observation of people or environments, protocols, and analytic techniques. Users can search for measures and details about how to use them, find measures in development, link to other measures registries and related resources, and submit new measures for inclusion.  

To learn about the features and uses of the registry, sign up for the May 19 webinar online.

As a reminder, a webinar on the features and uses of the NCCOR Catalogue of Surveillance Systems is scheduled for May 5. The catalogue, also an NCCOR product, is an interactive Web tool that provides one-stop access to a wide array of obesity-related data sources at multiple levels. Using the catalogue, researchers can identify data resources, compare attributes across systems, and link to other resources of interest. To register for the May 5 webinar, go online.