National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
November 16, 2010 • Volume 7 / Number 22

NEWS

HHS Secretary Kathleen Sebelius announced proposed graphic warning labels that will appear on cigarette packs and in advertisements.HHS Releases New Tobacco Control Strategy for the Nation

The U.S. Department of Health and Human Services last week unveiled a new comprehensive tobacco control strategy that seeks to help smokers quit and stop others from starting to use tobacco. One high profile piece of the plan will result in bolder health warnings that must cover the upper half of the front and back of cigarette packages and at least 20 percent of tobacco product advertisements beginning in 2012. Read more > >

SCIENCE SNAPSHOTS

A 3D in vitro assay that mimics the formation of vasculature in vivo. (Image courtesy of Dr. Enrique Zudaire) What is this? Click on the image to find out.
An image of a tube formation assay taken with an epifluorescence microscope. The tube formation assay is a 3D in vitro assay that mimics the formation of vasculature in vivo. NCI’s Dr. Enrique Zudaire is using this assay to discover new drugs to block tumor angiogenesis and tumor growth. The nuclei of endothelial cells appear blue. In green are the endothelial cells, which have been genetically engineered to express a green fluorescent protein. The thinner areas are hollow tubes while the thicker areas are cell clusters. (Image courtesy of Dr. Enrique Zudaire)
  

IN DEPTH

UPDATES

  • Legislative Update

    • The 111th Congress Winds Down
  • Cancer.gov Update

    • Boletín Showcases New Design and More Features
  • Notes

    • Biospecimens from SELECT and PCPT Now Available
    • Fraumeni Recognized for Achievements by American Cancer Society, American Italian Cancer Foundation
    • NCI Recognizes Clinical Investigators with Team Leadership Award
    • New Brochure on Biospecimens Available
    • New Issue of Cancer Health Disparities Newsletter Released
    • NCI Exhibit Booth Wins APHA Award

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

HHS Releases New Tobacco Control Strategy for the Nation

DHHS Secretary Kathleen Sebelius announced proposed graphic warning labels that will appear on cigarette packs and in advertisements. At a press conference on November 10, HHS Secretary Kathleen Sebelius announced proposed graphic warning labels that will appear on cigarette packs and in advertisements. [Enlarge]

The U.S. Department of Health and Human Services (HHS) last week unveiled a new comprehensive tobacco control strategy that seeks to help smokers quit and stop others from starting to use tobacco. One high profile piece of the plan will result in bolder health warnings that must cover the upper half of the front and back of cigarette packages and at least 20 percent of tobacco product advertisements beginning in 2012.

“We want to make sure that every person who picks up a pack of cigarettes knows exactly what the risk is they are taking,” said HHS Secretary Kathleen Sebelius during a November 10 press conference at George Washington University in Washington, DC, an event that also featured FDA Commissioner Dr. Margaret A. Hamburg and HHS Assistant Secretary for Health Dr. Howard Koh.

“This will be the most significant change to health warnings on cigarettes and in cigarette advertisements in more than 25 years,” said Dr. Hamburg. The Family Smoking Prevention and Tobacco Control Act, passed in 2009, granted the FDA authority to regulate the manufacture, marketing, and distribution of tobacco products, and the new warnings provide a concrete example of how that regulation can benefit public health, she added.

Other countries have implemented similar graphic warning labels on cigarette packages, noted Dr. Cathy Backinger, chief of NCI’s Tobacco Control Research Branch (TCRB) in the Division of Cancer Control and Population Sciences (DCCPS), and, based on research findings in recent years, Americans can expect that the new U.S. warning labels will help drive down smoking rates. “The data show that depicting the nature and magnitude of the harms of tobacco use in a realistic manner motivates smokers to quit,” she said.

Using the Evidence Base

The warnings are one part of what Secretary Sebelius called the first-ever comprehensive new strategy designed to help tobacco users quit and keep nonusers from starting. “The strategy rests on four pillars of strategic action,” added Dr. Koh, who co-chaired the working group that developed the plan. (See the sidebar.)

Proposed cigarette warning label with a graphic of a baby and the phrase, 'Warning: Tobacco Smoke Can Harm Your Children.' One of the proposed cigarette warning labels
Unpacking the Plan’s Actions

HHS Assistant Secretary for Health Dr. Howard Koh described the four pillars of strategic action that HHS would undertake as “high-impact interventions.”

Engage the public to change social norms around tobacco use. This effort will include a mass media campaign necessary to counteract the $34 million spent each day by major tobacco manufacturers on marketing. Department-wide messages and a multilevel communication and education campaign will be part of this initiative.

Improve the public’s health. By implementing and expanding evidence-based tobacco control interventions and policies at the state and community level, the goal is to enhance comprehensive cessation services, reduce tobacco-related disparities, increase the enforcement of current regulations, and accelerate the adoption of comprehensive smoke-free laws in every state.

Lead by example and leverage all possible resources. By maximizing all internal resources throughout the department, HHS will model tobacco-free campuses and facilities, including all conferences, as well as comprehensive cessation treatment, provider-education and training, and incentives for employees.

Advance knowledge, accelerate research, and expand the science base. This is especially critical given the FDA’s new authority to regulate tobacco. “The Department looks forward to working with partners around the country to make this vision come alive,” Dr. Koh said.

The objectives described in Ending the Tobacco Epidemic: A Tobacco Control Strategic Action Plan, revolve around a major metric––reducing the current rate of adult smokers from around 20 percent to 12 percent over the next decade by reducing the initiation of tobacco use by children, adolescents, and young adults, and helping current smokers successfully quit. The plan also includes reducing the exposure of nonsmokers to secondhand smoke and supporting the FDA’s role in regulating the manufacture, marketing, and distribution of tobacco products.

The plan outlines the following key actions: accelerating state and community tobacco control efforts, engaging the public by changing social norms with national media and communications, leading by example to implement model tobacco control policies within HHS, and advancing knowledge by expanding the science base and monitoring progress.

NCI scientists are involved in all four key action areas and DCCPS Director Dr. Robert Croyle represented NIH as co-chair of the steering committee that developed the plan. “We are gratified that NCI’s tobacco control research contributed to the Secretary’s new plan,” said Dr. Debbie Winn, deputy director of DCCPS. “As fewer Americans smoke, we will see fewer deaths from lung cancer and other diseases caused by tobacco use.”

NCI is one of a number of federal agencies contributing to both the implementation of the plan’s activities and building the research base on which it is founded. Dr. Backinger, whose branch has been funding tobacco control programs at the state and community level for years, will serve as co-chair of the subcommittee that monitors research and surveillance as the plan is implemented.

The Time Is Now

“We are truly at an unprecedented time in our nation’s public health history,” said Dr. Koh, who pointed out that the consequences of tobacco are epidemic. Whereas a million people died from tobacco-related causes in the 20th century, “the tobacco epidemic is projected to kill one billion people [worldwide] in the 21st century,” he said.

Lung cancer should be an uncommon disease in this country, he stressed, not the nation’s leading cause of cancer deaths. “This is all preventable,” he added. “For too long, the nation has been forced to tolerate the intolerable and accept the unacceptable.”

Dr. Michael Fiore, director of the University of Wisconsin’s Center for Tobacco Research and Intervention and one of many experts who helped craft the plan, explained why he agrees that this is an unprecedented time and opportunity for making advances in American public health.

“Among the most important public health achievements in the latter half of the 20th century was halving tobacco dependence in America from about 42 percent in the mid-1960s to just over 20 percent today,” he said. But that progress has been uneven, he added, because “tobacco has become concentrated among some of the members of our society with the least resources to overcome it, such as the poor, the least educated, and those with other mental and physical health conditions. There are enormous opportunities now to make a difference with these populations––including people who are on Medicare and Medicaid, for example.”

Dr. Fiore added that it will take more than the federal government to make full use of these opportunities. “HHS and the whole government can provide leadership,” he said, “but it will require a full partnership with the research and private-sector communities in order to make the objectives in this plan a reality.”

—Addison Greenwood

To Learn More

HHS has posted a full copy of the strategic plan, along with the related press release and a Webcast of the press announcement, online.

Examples of each of the proposed cigarette warning labels can be found on the FDA Web site.

NCI has many resources to help people quit smoking, including a Web page with links to fact sheets, quit guides, and other tools and information, and the NCI Smoking Quitline at 1-877-44U-QUIT (1-877-448-7848).

Cancer Research Highlights

Mutated Gene Linked to Poor Survival in Acute Myeloid Leukemia

Researchers have identified a gene that is frequently mutated in a subset of patients who have acute myeloid leukemia (AML), and these patients tend to have significantly worse outcomes than patients who have normal copies of the gene. If the findings are confirmed, then clinical trials could investigate whether giving patients with the mutated gene more intensive therapy early in treatment helps them live longer, said Dr. Timothy Ley of the Washington University School of Medicine in St. Louis and his colleagues. Their findings were reported online in the New England Journal of Medicine on November 10.

The mutations were found in 62 of 281 patients (22 percent) with AML and occurred throughout a gene called DNA methyltransferase 3A (DNMT3A), which plays a role in fetal development and is active in blood-forming cells later in life. Although the researchers do not yet know how the mutations contribute to the disease, the median overall survival of patients who had the mutations was 12.3 months compared with 41 months for patients without the changes. All of the mutations were associated with poor overall survival, which suggests that they “have an important common effect on the potential of AML cells to cause lethal disease,” the researchers wrote.

The mutations were most often found in patients classified as having “intermediate-risk” disease, based on an analysis of their chromosomes (56 of 166 patients, or 33.7 percent), and the changes were absent from all 79 patients who had a favorable-risk profile. The intermediate-risk group includes patients who may or may not respond to standard treatments, and doctors currently cannot distinguish these individuals. The new findings suggest that DNMT3A mutations could be a biological marker for identifying patients at risk of poor outcomes, the researchers said.

“Patients who have the DNMT3A mutations have poor outcomes across the board,” said Dr. Ley. “It’s really striking.” His team discovered the first DNMT3A mutation when resequencing the cancer genome of a woman who relapsed and died of recurrent AML 2 years after initial diagnosis. The researchers had sequenced normal and cancer genomes from this patient in a study reported in 2008. But it was only when they went back and analyzed her DNA using newer sequencing technologies that they found the change involving DNMT3A.

See also: A Cancer Genome Is Sequenced, Revealing Rare Mutations

Novel Drug Effectively Shrinks Tumors in Hodgkin Lymphoma

An investigational drug composed of a monoclonal antibody linked to a potent chemotherapy agent led to complete or substantial tumor shrinkage in nearly 40 percent of patients with Hodgkin lymphoma in a phase I clinical trial, researchers reported last week. The results were published November 4 in the New England Journal of Medicine.

In the trial, 42 patients with Hodgkin lymphoma and three patients with anaplastic large-cell lymphoma (ALCL) who had relapsed after earlier treatments (including stem cell transplantation) or were resistant to standard treatments received the drug brentuximab vedotin (SGN-35). The antibody component of the drug targets a protein called CD30 that sits on the surface of lymphoma cells. Attached to the antibody is a powerful investigational chemotherapy agent called monomethyl auristatin E (MMAE).

Developed by Seattle Genetics, MMAE is 100 to 1,000 times more potent than other chemotherapy drugs, according to the company. The antibody directs the drug to cancer cells, where it is absorbed and degraded by enzymes in the cells’ nuclei, releasing the MMAE and leading to cell death.

Among the 17 patients who had measurable responses, 11 had no evidence of existing cancer (complete response) after treatment, and the remainder had at least 50 percent tumor shrinkage (partial response). Because it was a phase I trial, patients received different doses. Among the 12 patients who received the most effective dose for which side effects were the least severe (the maximum tolerated dose), six had a measurable response. Overall, 86 percent of patients in the trial had at least some tumor shrinkage and side effects were limited.

Over the last 3 decades, there has been little progress in developing new treatments for Hodgkin lymphoma. So, these results offer significant promise for patients, said the study’s lead investigator, Dr. Anas Younes of the University of Texas M. D. Anderson Cancer Center. “I think it is remarkable that the majority of patients had tumor reductions when they were treated on the phase I study,” he wrote in an e-mail.

Initial results from a phase II trial of the drug in the same patient population appear to be even stronger than the phase I results, according to Seattle Genetics. In late September, the company announced that 75 percent of the 102 patients in the phase II trial, all of whom had relapsed/refractory Hodgkin lymphoma, had an objective response. And, in early October, the company reported that patients with ALCL in another phase II trial of brentuximab had an 86 percent measurable response rate. More complete results and details from both trials will be presented at the American Society of Hematology annual meeting in early December.

Indefinite Imatinib Therapy May Not Be Necessary for Some CML Patients

Findings from a small clinical trial in France suggest that some patients with chronic myelogenous leukemia (CML) may be able to stop treatment with the tyrosine kinase inhibitor (TKI) imatinib mesylate (Gleevec) without the disease returning. The results indicate that some patients may be cured by imatinib and similar therapies and may not need to remain on therapy permanently, the study authors concluded in the November 2010 Lancet Oncology.

The trial involved 100 patients who had maintained a complete molecular response (no evidence of disease) for 2 years on imatinib and then stopped taking the drug. Sixty-nine of the patients had been followed for a median of 24 months, and, among these, nearly 40 percent remained disease free for at least a year after discontinuing imatinib therapy. For patients whose disease returned, in nearly every case the recurrence happened within 6 months of stopping treatment, and all patients responded to the re-initiation of imatinib therapy, although not all of them obtained a second complete response.

The fact that these patients “retained sensitivity to the drug … [suggests] that discontinuation does not lead to acquired resistance to imatinib and does not raise any further safety issues,” wrote Dr. Francois-Xavier Mahon and his colleagues. Sustained remissions on imatinib are not common, they continued, “so patients treated with imatinib who are candidates for treatment interruption are rare.”

The researchers identified several factors that were predictive of which patients were most likely to remain in remission after therapy discontinuation, including male gender, a remission lasting more than 4 years, and a good prognosis at diagnosis based on a standard prognostic tool.

While research in this area continues—including whether superior results could be achieved with second-generation TKIs such as dasatinib (Sprycel) and nilotinib (Tasigna) that have the same molecular target as imatinib and are approved for CML treatment—discontinuation of imatinib should be done “only in the context of an ongoing clinical trial,” the authors cautioned.

In an accompanying commentary, Dr. Peter Valent from the Medical University of Vienna agreed that “there is now hope for drug-induced cure in CML.” However, he continued, more work is needed to answer important questions. “Clinical trials will define the curative potential of novel TKIs and of various drug combinations in the future,” he said.

Lasofoxifene Is Potential New Option for Breast Cancer Risk Reduction

An investigational agent in the same family of drugs as tamoxifen and raloxifene may be as or more effective in reducing breast cancer risk in some women, according to the findings of a large clinical trial. The drug, lasofoxifene, also appears to have important benefits for both bone and heart health and, with one exception, appears to lack the rare but potentially serious side effects associated with tamoxifen and raloxifene. The results were published online November 4 in the Journal of the National Cancer Institute.

The findings come from a randomized clinical trial called PEARL, in which more than 8,500 postmenopausal women with osteoporosis were randomly assigned to take a placebo or one of two different doses of lasofoxifene (0.25 mg or 0.5 mg) daily for 5 years. Initial results, based on 3 years of follow-up, showed a reduced risk of estrogen receptor (ER)-positive breast cancer in women who received the higher dose of lasofoxifene compared with the placebo.

The new, more mature results, which provide 5 years of participant follow-up, show the overall risk of breast cancer was reduced by 79 percent, and the risk of invasive ER-positive breast cancer was reduced by 83 percent in women who took 0.5 mg of lasofoxifene compared with women who took the placebo.

There was some risk reduction seen with the lower dose of lasofoxifene, but it was not statistically significant, reported Dr. Andrea LaCroix of the Fred Hutchinson Cancer Research Center and her colleagues. Women who took the higher lasofoxifene dose also had statistically significant reductions in the risk of vertebral and nonvertebral fractures, cardiac events, and strokes. The only notable side effect was an increased risk of blood clots.

The researchers also conducted a nested case-control study that included all 49 cases of breast cancer in the trial and 156 women from the trial’s placebo arm. Women with higher levels of the hormone estradiol at study entry, they found, seemed to gain a greater cancer prevention benefit from lasofoxifene, but the difference was only statistically significant for total breast cancer incidence, not ER-positive breast cancer.

“We need more complete information about the long-term effects of lasofoxifene on both beneficial and unfavorable outcomes,” cautioned Dr. Victor Vogel of the Geisinger Medical Center in an accompanying editorial. Although women in the trial were, on average, significantly younger than participants in the STAR trial, which affirmed the breast cancer risk reduction benefits of both tamoxifen and raloxifene, they were also at lower overall risk of breast cancer (based on their Gail model scores).

Nevertheless, given the “dramatic” risk reduction seen with lasofoxifene in the PEARL trial, Dr. Vogel called the findings “encouraging.” Lasofoxifene is still an investigational agent. In May, Pfizer, which manufactures the drug, withdrew its application to the FDA to market the drug for the treatment of osteoporosis. According to a company spokesperson, Pfizer is investigating several options for the drug, including selling it to another company.

Some Cells in Stroma May Block Immune System’s Antitumor Effects

Researchers have identified a population of cells in the stroma—the supporting connective tissue of an organ—that may prevent the immune system from attacking or inhibiting the growth of tumors. When this subset of stromal cells was deleted in mice, relatively small tumors in the animals stopped growing, Dr. Douglas Fearon of the University of Cambridge, United Kingdom, and his colleagues reported November 5 in Science.

Cancer biologists have long wondered why the human immune system frequently appears to be suppressed in the tumor microenvironment. One factor in this phenomenon, Dr. Fearon and his colleagues now propose, may be stromal cells that express a protein called the fibroblast activation protein (FAP) on their cell surface. Although the results need to be confirmed in humans, they could help explain, for instance, why vaccines designed to boost a patient’s immune response against cancer have had limited success, the researchers said.

The suppression of the immune system by FAP-positive cells “may be a developmentally programmed, tissue-protective function that, in the context of a tumor, is catastrophically inappropriate,” the study authors wrote.

These results support other studies suggesting “that immunizing against fibroblasts in tumors can unmask an immune response to cancer,” wrote Drs. Hans Schreiber and Donald Rowley of the University of Chicago in an accompanying editorial. They noted that eliminating FAP-positive cells should inhibit the growth of small spontaneous tumors and, therefore, may help eliminate clinically undetectable cancer cells that have already metastasized before a primary tumor is surgically removed.

A Closer Look

Technology
This is the fifth article in a series of stories about new technology for cancer diagnosis or treatment. View a list of articles in this series.

Low-Dose CT Shows Clear Mortality Benefit for Lung Cancer Screening in Heavy Smokers

At a press conference on November 4, NCI released initial results from the National Lung Screening Trial (NLST), showing that current or former heavy smokers between the ages of 55 and 74 who underwent screening with low-dose helical computed tomography (helical CT) experienced 20 percent fewer deaths from lung cancer than a group of peers who received screening with standard chest x-rays.

“This is really the first clear demonstration that a screening procedure can be effective in reducing mortality from lung cancer,” said Dr. Douglas Lowy, deputy director of NCI, at the press conference.

CT machine at the NIH Clinical Center capable of performing low-dose helical imaging (Photo by Daniel Sone) This 356-slice Toshiba scanner is used by staff in the Radiology Department at the NIH Clinical Center to perform low-dose helical CT and other types of CT imaging. (Photo by Daniel Sone, NCI)

“This finding has important implications for public health, with the potential to save many lives among those at greatest risk for lung cancer,” commented NCI Director Dr. Harold Varmus. However, he clarified, “I don’t want you to come away from this announcement believing that it’s now safe to continue to smoke or to start smoking. Screening does not prevent lung cancer and it does not protect the large majority of subjects from death from lung cancer. Not smoking and quitting smoking remain important public health goals and remain the best defenses against lung cancer.”

Strength in Trial Design

NLST represents a collaboration of the Lung Screening Study group in NCI’s Division of Cancer Prevention and the American College of Radiology Imaging Network (ACRIN), which is sponsored by NCI’s Division of Cancer Treatment and Diagnosis (DCTD). The trial was conducted at 33 trial sites across the nation. 

Recruitment and retention were achieved in partnership with the American Cancer Society, which raised awareness of the trial at the local community level through the activities of the Society’s regional offices. The first NLST participants were enrolled in August of 2002, and the target goal of 50,000 participants was achieved by January 2004. Final enrollment included more than 53,000 people. 

The large number of participants in this trial, as well as its randomized design, helped to ensure that NLST would provide a definitive answer as to whether helical CT screening helps prevent deaths from lung cancer. Another element that strengthened the findings is that the trial’s main endpoint was the number of deaths from lung cancer, not just the number of lung cancers detected by screening.

NLST was stopped at the request of the trial’s independent Data and Safety Monitoring Board, which determined on October 20 that all data needed to answer the trial’s primary question had been collected. Intriguingly, the initial results showed a 7 percent decline in death from any cause (including lung cancer) in the low-dose helical CT group, though NLST researchers do not yet understand all the factors contributing to this reduction. “Within the next few months, [the full] results will be promptly published in a peer-reviewed journal with full and immediate access to the public,” said Dr. Richard Fagerstrom, one of the lead statisticians for NLST.

Looking Inside the Body, Not Through the Body

CT scanners capture images in slices or in a helical, continuous image. Most CT scanners can gather images in parallel slices (Figure A) or as one helical, continuous image (Figure B) that is reconstructed by a computer program.

Previous trials testing the efficacy of chest x-rays for lung cancer screening have produced uniformly disappointing results. Although x-rays have the advantage of using an extremely low dose of radiation to image the body’s tissues, the technology is limited in the size and location of the abnormalities it can detect.

“A chest x-ray can find a nodule down to about 1 cm [in diameter] reliably, depending on where it’s located,” explained Dr. David Bluemke, director of Radiology and Imaging Sciences at the NIH Clinical Center. “In some parts of the lungs around the middle of the blood vessels, it needs to be larger than that. On a chest CT scan, nodules can be seen clearly at 1 to 2 mm in size.

“In addition, on a chest x-ray, you are trying to look through a wealth of other anatomical information, including the bones and the blood vessels, to find a nodule,” he continued. “In a chest CT there is very little that’s hiding that nodule—you’re looking inside the patient instead of through the patient.”

When CT entered the clinic in the 1970s, the scanners slowly gathered images in parallel slices (see Figure A), leaving small information gaps that had to be reconstructed by a computer program. In the 1990s, helical CT (also called spiral CT) technology emerged, gathering continuous pictures of the body in a rapid helical motion (see Figure B), so there are no gaps in the pictures collected.

“When it was first clear that CT scans were so much more precise than x-rays, people started looking at potentially developing them for screening purposes, but the limitation had always been the capabilities of the machine,” commented Dr. Giuseppe Giaccone, chief of the Medical Oncology Branch and head of the Thoracic Oncology Section in NCI’s Center for Cancer Research. “But the development in scanners over the last decade or so has been tremendous. In the ‘90s, doing a scan would take minutes. Now you hold your breath, and it’s done,” he added.

“It’s the speed of helical CT and also the overlapping nature of the slices that make it possible to find small nodules in the lung,” said Dr. Christine Berg, NCI project officer for NLST. “So the helical scanning technology was critical for screening applications, and also the realization that you could probably see things just as well if you turned the dose down. The concern about radiation dose has been around for a long time, and the dose used for screening [in NLST] is substantially less than the dose of a diagnostic CT,” she explained.

Cautions and Caveats

“The results of this trial provide objective evidence of the benefits of low-dose helical CT screening in an older, high-risk population, and suggest that, if low-dose helical CT screening is implemented responsibly, and individuals with abnormalities are followed judiciously, we have the potential to save thousands of lives,” said Dr. Denise Aberle, the NLST national principal investigator for ACRIN. “However, given the high association between lung cancer and cigarette smoking, the trial investigators re-emphasize that the single best way to prevent lung cancer deaths is to never start smoking, and if already smoking, to quit permanently.”

One major caveat to the findings is that, for now, the researchers can only comfortably extrapolate the results to the population that participated in the trial—current or former smokers (defined as having quit within 15 years of trial entry) between the ages of 55 and 74 who smoked the equivalent of at least a pack a day for 30 years.

“The NLST findings should not be interpreted to mean the general public should now get regular CT scans,” cautioned Dr. Lowy. “This trial answered specific questions about a well-defined high-risk population. Further analysis and modeling of NLST data will be needed before specific recommendations can be made about the possible broader use of this screening method.”

At this time, NCI is not releasing recommendations for the use of lung screening CT for any population. Once the final data have been fully analyzed and published, explained Dr. Varmus, recommendations will be made by any of several bodies commonly called upon to make medical service recommendations, including the United States Preventive Services Task Force and the American Cancer Society.

The potential harms of lung cancer screening, which exist alongside the potential benefits, will also need to be factored into any future recommendations. Approximately 25 percent of all scans in the trial showed false-positive results, meaning that on follow-up the observed abnormalities turned out not to be cancer. All of the affected patients underwent some kind of additional diagnostic procedure, ranging from follow-up diagnostic CT scans, which use higher doses of radiation, to lung biopsy and, in some cases, thoracotomy (surgical opening of the chest), all of which carry risks, explained Dr. Giaccone.

“This will be an important consideration in drawing up recommendations for how this technology should be used even in this high-risk group,” said Dr. Varmus at the press briefing.

According to Dr. Giaccone, the risk of false-positive results and unnecessary follow-up procedures may become more of an issue as lung screening CT is adopted in the wider medical community. “As this becomes more widespread in community hospitals and small practices, there will be a learning curve,” he explained.

However, guidelines for both dose and evaluation of abnormalities found on screening are already publicly accessible, explained Dr. Berg. ACRIN has posted parameters for low-dose scanning that were used during this study. And the Fleischner Society, an international, multidisciplinary medical society for thoracic radiology, has published guidelines for the evaluation of lung nodules found on CT scans.

“So the metrics for acquiring the images and the metrics for interpreting abnormalities are already accessible to the community,” said Dr. Berg. “They just need to be followed.”

—Sharon Reynolds

More Information about the National Lung Screening Trial can be found online:

Spotlight

Uncertain Road for Potential Ewing Sarcoma Therapy

At the 2010 American Society of Clinical Oncology annual meeting, Dr. William Tap of UCLA’s Jonsson Comprehensive Cancer Center described the case of a young patient with Ewing sarcoma, who, as part of a phase I clinical trial, had been treated with an investigational monoclonal antibody, AMG 479. The antibody blocks the activity of a growth factor receptor known as the type 1 insulin-like growth factor receptor, or IGF-1R.

Eight days after the first treatment, the patient’s tumors began to shrink. Three years later, continuing to receive the drug, the patient was still cancer free. Eleven other patients in the trial had tumors in the Ewing family of sarcomas. A second patient experienced some tumor shrinkage but had to leave the trial because of a bone marrow disorder. The remaining 10 patients, Dr. Tap explained, “did not respond to AMG 479 therapy.”

This experience is almost identical to what has been seen in early human trials of other IGF-1R inhibitors, all monoclonal antibodies, in patients with Ewing and other sarcomas: some good responses—including partial tumor shrinkage and sustained periods of stable disease, in addition to a handful of patients with complete tumor eradication—but little more.

In a rare cancer where you have a targeted therapy that you know only a subset of patients are going to respond to, you need big international studies.

—Dr. Lee Helman

“The extent of activity in Ewing sarcoma is nearly identical to what was seen with trastuzumab (Herceptin) in breast cancer when it first went into phase II testing,” said Dr. Laurence Baker of the University of Michigan, who, as director of the Southwest Oncology Group, has been involved in a number of trials testing new treatments for sarcomas.

But Ewing sarcoma affects only 400 to 500 mostly younger patients a year in the United States, in stark contrast with the comparatively vast population of patients who develop breast cancer. And, unlike trastuzumab, which has overexpression of the protein HER2 as a biomarker to identify patients who are most likely to respond to the drug, no such biomarker yet exists for the IGF-1R inhibitors under investigation.

That reality has raised doubts in some corners about whether these agents can complete the often perilous journey to the clinic. Those doubts have even caused one large pharmaceutical company to halt development of its IGF-1R inhibitor.

Nevertheless, the drugs deliver “an unbelievable benefit in some patients,” stressed Dr. Lee Helman, the scientific director of NCI’s Center for Cancer Research, who has been at the forefront of efforts to develop new therapies for Ewing and other sarcomas, including the IGF-1R inhibitors. But, he conceded, “it’s clear we still have a lot of work to do.”

Inching Forward

A phase II clinical trial called SARC 011 was designed to help answer some of the most pressing questions about these agents, including biomarkers that may identify patients who should receive them. Launched by its namesake, the nonprofit Sarcoma Alliance for Research through Collaboration, the trial involved the monoclonal antibody known as R1507, which had been manufactured by Roche. But, in December 2009, while the trial was in progress, Roche announced it was halting development of R1507.

The decision had immediate repercussions. The SARC 011 trial would have to be halted prematurely, at a time when enrollment of an “enrichment cohort”—a group of  patients who, based on data accumulated in the trial, the investigators suspected may be more likely to respond to the drug—was at six patients, when the target was 30. Also, a planned phase II trial combining R1507 with chemotherapy, already approved by the FDA to proceed, would have to be scrapped.

The company’s decision “has been a source of frustration,” Dr. Helman admitted. “I have a patient who has been on [R1507] for the last year,” he said. “She’s back in school and she’s doing well.” Whether this particular agent will resurface, he said, is unknown.

In total, SARC 011 enrolled 321 patients, 135 of whom had Ewing sarcoma. In pursuing the trial, SARC had reached out to other companies developing IGF-1R inhibitors to see if any would support a large international phase II trial but let the SARC investigators control the study, explained the group’s president, Denise Reinke, an oncology nurse at the University of Michigan. They found a partner in Roche.

“Accrual was incredibly brisk,” she explained. “The trial opened in December 2007, and by December 2008 we had 220 patients on the study, and 75 were Ewing patients.”

In order to get a sufficient number of patients for such a rare cancer—enough to supply the statistical power needed to get a good indication of the drug’s efficacy as a single agent—an international trial was needed. “In a rare cancer where you have a targeted therapy that you know only a subset of patients are going to respond to, you need big international studies,” Dr. Helman said.

The rarity of the disease also makes it important to ensure that trials testing new treatments are designed to answer the most important scientific questions, he added, which makes collaboration all the more important.

The SARC 011 trial has concluded and the research team has a manuscript with the most up-to-date findings, Reinke said. In the meantime, with Roche’s exit from this drug class and trials testing IGF-1R inhibitors in more common cancers (including lung and colorectal cancer) failing to show survival improvements, some researchers are putting a lot of eggs in the SARC 011 basket. The trial’s results “are likely to be pivotal to the future of this family of targeted therapies in sarcoma,” wrote Dr. David Olmos and his colleagues from the Royal Marsden NHS Foundation Trust in London earlier this year.

The Broader Landscape

We don’t understand what is different about those patients who have responded, so [developing biomarkers] is really one of the next critical steps.

—Dr. Suman Malempati

As for the future of these agents, there is near-unanimous consensus about what needs to happen. “We don’t understand what is different about those patients who have responded, so [developing biomarkers] is really one of the next critical steps,” said Dr. Suman Malempati of Doernbecher Children’s Hospital/Oregon Health & Science University, who has been involved in two early-phase trials of an IGF-1R inhibitor called cixutumumab, which is being developed by Imclone under a Cooperative Research and Development Agreement with NCI.

The drugs also need to be tested in combination with cytotoxic therapies, Dr. Baker stressed. “Everything we know suggests that most [targeted therapies] are better in combination than alone,” he said. Based on lab and animal model studies, Dr. Baker continued, “there’s every reason to believe that, if these agents can be combined with chemotherapy, they will have good synergy.”
 
Testing IGF-1R inhibitors in combination with other therapies should provide “an entrée with indication of how to go forward,” agreed Dr. Jeffrey Toretsky of Georgetown University’s Lombardi Comprehensive Cancer Center. Based on the results in human trials to date, he continued, “I just wouldn’t know how to incorporate them as a single agent into current therapy.”

One combination trial of an IGF-1R inhibitor in sarcoma is moving ahead. Dr. Malempati is leading a pilot study, sponsored by the Children’s Oncology Group (COG), that will test the addition of cixutumumab with or without temozolomide to a multidrug chemotherapy regimen in patients with rhabdomyosarcoma. COG is also in discussions with Pfizer to conduct trials of its IGF-1R inhibitor figitumumab in patients with Ewing sarcoma, said the group’s chair, Dr. Gregory Reaman, which they hope can include a combination therapy trial.

But the onus isn’t all on monoclonal antibodies that target IGF-1R. Several companies also have IGF-1R-targeted small-molecule drugs that may make their way into early human trials. Because they tend to be less specific for their intended targets, small molecules can be a double-edged sword, explained Dr. Malempati. Weaker specificity can be advantageous, he said, “because you may be able to inhibit other processes that aid the cancer.” However, he continued, “it also means that you can have more off-target side effects.” (See the box below.)

Regardless of what kind of agent is used to inhibit its activity, the extent of the therapeutic advantage to be gained by targeting IGF-1R is unclear, Dr. Toretsky believes. But, he continued, enough has been accomplished to date that further research on these agents “needs to be done so that we can fully vet their potential.”

Carmen Phillips

So a Small Molecule Meets a Fusion Protein…

In October 2010, Dr. Toretsky received a nearly $4.4 million grant from NCI, under the American Recovery and Reinvestment Act, to further the development of a small molecule inhibitor that he hopes will prove useful in Ewing sarcoma. The compound, however, doesn’t target IGF-1R. Rather, it targets a fusion protein, EWS-FLI1—the product of a chromosomal translocation in which parts of the EWS and FLI1 genes are fused together—that is present in many Ewing sarcoma tumors and appears to be an important driver of the disease.

Still in the preliminary stages, this approach is highly novel in targeted therapy because the small molecule Dr. Toretsky and his colleagues are investigating is the first to block a fusion protein from adhering to another protein that it requires to drive tumor formation.

“We knew we would have to find critical partners of the fusion in order for it to work,” Dr. Toretsky explained. They eventually found that partner, the protein RNA helicase A (RHA). They then mined an NCI library of 3,000 small molecules to see if any would bind to EWS-FLI1. They were successful, and fortunate, because the same molecule also blocked the fusion protein from binding to RHA. Working with chemists at Lombardi, they developed an analog of this molecule that was a more potent inhibitor of the proteinprotein binding, called YK-4-279.

“The NCI grant provides support for pharmacokinetics, toxicology, and, assuming our studies indicate that it’s a reasonable thing to do, filing of an Investigational New Drug application with the FDA to begin human trials,” Dr. Toretsky explained. The research takes time, but it can’t move fast enough.

“I’m getting two to three e-mails a week from families of patients with Ewing,” he said.

Featured Clinical Trial

Combination Therapy for Advanced Kaposi Sarcoma

Name of the Trial
Pilot Study of Liposomal Doxorubicin Combined with Bevacizumab Followed by Bevacizumab Monotherapy in Adults with Advanced Kaposi Sarcoma (NCI-09-C-0130). See the protocol summary.

Dr. Robert Yarchoan and Dr. Thomas Uldrick
Drs. Robert Yarchoan and Thomas Uldrick

Principal Investigators
Dr. Robert Yarchoan and Dr. Thomas Uldrick (Lead Associate Investigator), NCI Center for Cancer Research

Why This Trial Is Important
Kaposi sarcoma (KS) is a rare type of cancer that produces tumors with abnormally dense and irregular blood vessels. These blood vessels leak red blood cells into the surrounding tissue, giving the tumors a characteristic dark appearance. KS tumors can form beneath the skin, in the mucous membranes of the mouth, nose, and throat, or along the gastrointestinal tract. The lymph nodes, lungs, and other organs may also be affected, especially in advanced cases. There are several different types of KS that are defined by the populations they most commonly affect. KS is caused by a virus called Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8).

Patients with advanced KS are often treated with a drug called liposomal doxorubicin. Although many patients respond to this treatment, some require long-term therapy that may exceed the maximum cumulative dose recommended for this drug. In addition, liposomal doxorubicin belongs to a class of drugs called anthracyclines, which may decrease the number of critical CD4-positive T lymphocytes in patients with HIV-associated KS. Therefore, researchers are looking for targeted therapies for KS that may decrease the amount of liposomal doxorubicin administered, particularly the amount given over a patient’s lifetime.

Increased production of a protein called vascular endothelial growth factor (VEGF), which stimulates the formation of new blood vessels (angiogenesis), is thought to be one factor that contributes to the abnormal growth of blood vessels in KS tumors. Therefore, researchers have been interested in seeing whether KS might respond to bevacizumab, a monoclonal antibody that blocks angiogenesis by targeting VEGF.  In an earlier study conducted by NCI’s HIV and AIDS Malignancy Branch, bevacizumab showed promising activity against KS in patients with the classic and HIV-associated forms of the disease, especially in patients with certain manifestations of KS, such as pleural effusions and tumor-associated edema. Now, these researchers want to see if combining bevacizumab with liposomal doxorubicin will be effective in shrinking KS tumors in patients with advanced disease. 

In this clinical trial, adult patients with any form of advanced KS will be treated with liposomal doxorubicin and bevacizumab every 3 weeks for a maximum of six treatments. Patients who respond to this therapy or have stable disease will receive bevacizumab alone every 3 weeks for a maximum of 11 treatments. Doctors will evaluate the overall response rate, safety, and 12-month progression-free survival associated with this treatment regimen.

“The HIV and AIDS Malignancy Branch at NCI has been heavily involved in the development of effective therapies for KS for over 20 years.  As our knowledge about the biology of KSHV-related cancers improves, we continue to evaluate less toxic therapies for KS patients,” said Dr. Uldrick. “This is important because some patients may have a waxing and waning course with their disease and may need multiple treatments over their lifetimes, particularly given the aging of the HIV-infected population in the United States. One of our goals is to decrease the amount of cytotoxic chemotherapy that patients are exposed to over the course of their lifetime.

“The current study builds on our previous one of bevacizumab alone in KS,” he added. “We hope this combination will allow for the rapid treatment of advanced KS while being less toxic and requiring less anthracycline in the long-run than would otherwise be needed.”

For More Information
See the lists of eligibility criteria and trial contact information or call the NCI Clinical Trials Referral Office at 1-888-NCI-1937. The call is toll free and confidential.

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

Community Update

Families and Scientists Gather to Discuss Research and Treatment for Li-Fraumeni Syndrome

Earlier this month, about 200 people gathered at the NIH Natcher Conference Center for an international workshop to review the current status of research on a rare, inherited disorder known as Li-Fraumeni syndrome (LFS). In attendance were researchers, clinicians, genetic counselors, and members of approximately 40 families that are affected by the disease. Drs. Sharon Savage and Phuong Mai, of the Clinical Genetics Branch in NCI’s Division of Cancer Epidemiology and Genetics (DCEG), organized the workshop.

“I’m only 40 years old,” a woman in the audience shared after listening to a panel of patients speak about LFS. “I’ve lost a child to cancer, and I’ve had cancer six times. I [knew of] no one else who has this [syndrome].” Moved to tears, she went on to describe the experience of dealing with the fear of cancer every day and knowing that her surviving daughter could be diagnosed with cancer at any time. “I have cancer right now,” she said, “and it’s just so overwhelming to hear someone else’s story and know that I’m not alone anymore.”

…it’s just so overwhelming to hear someone else’s story and know that I’m not alone anymore.

—LFS survivor in audience

Li-Fraumeni syndrome was first described in a 1969 publication in the Annals of Internal Medicine by Dr. Joseph F. Fraumeni, Jr., the director of DCEG, and his colleague Dr. Frederick P. Li. They described four families in which several members developed a wide variety of cancers as children or young adults. Many of the patients had multiple primary tumors, most notably breast cancer, soft tissue and bone sarcomas, brain tumors, adrenocortical neoplasms, and acute leukemia. Subsequent studies identified additional families that met the classic criteria for LFS. Other families had similar but less pronounced aggregations of cancer and were classified as Li-Fraumeni-like (LFL).

Families with LFS have been found to have inherited mutations in the TP53 gene, a tumor suppressor gene involved in numerous cellular processes, including DNA repair and apoptosis. But only about 70 percent of families with classic LFS and 40 percent of LFL families carry these mutations, so the genetic determinants in other patients remain unknown. “We need a coordinated global effort if we are to succeed against this rare disorder,” Dr. Fraumeni said at the start of the meeting. “This is a very exciting time in cancer genomics, and research on this syndrome can take full advantage of the opportunities and technologies these advances provide.”

Reflecting on Success and Teamwork

Dr. Louise Strong from the University of Texas M. D. Anderson Cancer Center discussed the history of research on LFS, including the early work of scientists who persisted in tracking families that showed characteristics of the syndrome while collecting biospecimens for future molecular studies. One of the many positive outcomes of the workshop was the establishment of a new LFS clinical research consortium to develop protocols that require pooling of data and resources. This international collaboration will focus on improvements in screening, treatment, and prevention, as well as interdisciplinary research into the mechanisms underpinning multiple-cancer syndromes such as LFS.

Presenters at the Li-Fraumeni Syndrome Workshop included researchers, clinicians, patients, and advocates. The workshop brought together members of the clinical, research, patient, and advocacy communities to discuss what is known about the genetics and molecular biology of LFS, as well as the psychosocial consequences of LFS for patients, and how members of the group can work together to improve outcomes from future research.

During a panel that included patients and their families, Oliver Wyss told the audience, “We have to look at this workshop as a gathering of one big family, working against this devastating disease to find a cure.” Wyss was diagnosed with severe aplastic anemia at the age of 22 after coming to the United States to play professional soccer. He recovered from the disease and has been healthy ever since, but, when his son was diagnosed at the age of 10 months with choroid plexus carcinoma, an extremely rare tumor, the family was tested and learned that they all carry a germline TP53 mutation that causes LFS. His son died at age 3 after numerous rounds of surgery, chemotherapy, and radiation treatments. In addition, his daughter was recently diagnosed with adrenocortical carcinoma.

“I believe I speak for all of the families here [when I say] there isn’t enough going on. We can’t just be satisfied by screening for cancer,” he said. “We have to find true cures for these genetic disorders. As families, we’re willing to do more, to give back.”

Reflecting on the successful workshop and development of a consortium, Dr. Savage said, “through our ongoing study of LFS families at NCI and through our collaborative approach we hope to not only help those with the disorder but also provide clues for future research into the genetic underpinnings of nonfamilial tumors.”

Focusing on the Future

During a plenary session on the clinical aspects of LFS, Dr. Maria Isabel Waddington Achatz of São Paolo, Brazil, described studies of high-risk families that feature adrenocortical tumors in children. She estimated that, in the southeastern portion of Brazil, one in every 300 people is the carrier of a distinctive founder mutation in TP53.

Other plenary sessions at the meeting addressed concerns related to genetic counseling for LFS and LFL patients, the psychosocial aspects of having the disorder, and the molecular biology of TP53. Participants met in smaller groups at the end of the workshop to discuss how they could work together to hasten progress in clinical and interdisciplinary research and how to establish a family support network for those who deal with this disorder every day.

“I was truly delighted to participate in this historic event,” said Dr. Fraumeni. “This is an exciting time for research on LFS. The new consortium of investigators that pools expertise and resources, combined with the development of an advocacy organization to support families, holds great promise for this important field of study.”

An archived video of the full meeting is available through the NIH Videocast Web site.

The Clinical Genetics Branch in DCEG is currently accepting referrals for an LFS clinical research protocol. Additional information about the NCI LFS program and about the clinical research workshop can be found at: http://lfs.cancer.gov/

Legislative Update

The 111th Congress Winds Down

The imminent final adjournment of the 111th Congress will mark the end of a remarkable period of legislative history distinguished by the infusion of economic stimulus funds into the federal budget, the passage of broad health care reform, and tobacco regulation, among other actions.

The 111th Congress convened for the first of its two year-long sessions on January 6, 2009, amid an economic recession and a relatively flat annual appropriations trend for NCI. Among the first laws enacted by this Congress was the American Recovery and Reinvestment Act of 2009 (ARRA; P.L. 111-5, signed into law on February 17, 2009), an economic stimulus package that injected $10 billion into the NIH budget, yielding NCI $1.3 billion to be used over fiscal years 2009 and 2010 for high-impact projects that could be completed within 2 years. ARRA also channeled $1.1 billion to the Department of Health and Human Services to be used for comparative effectiveness research (CER) and authorized a Federal Coordinating Council for CER.

Congressional negotiations on the ARRA legislation unfolded simultaneously with the regular appropriations process for fiscal year 2009. The Fiscal Year Omnibus Appropriations Act (P.L. 111-8, signed into law on March 11, 2009) included an appropriation of $4.97 billion for NCI, representing a modest increase of 2.8 percent over the prior year’s funding. Fiscal year 2010 appropriations were included in the Consolidated Appropriations Act, 2010 (P.L.111-117, became law on December 16, 2009), which provided $5.10 billion to support NCI’s programs.

In the Wake of Reform

Health care reform was one of the most important agenda items for the 111th Congress, and on March 23, 2010, President Obama signed the Patient Protection and Affordable Care Act into law. This broad, landmark legislation incorporated, among its numerous provisions, several separate bills of particular interest to the cancer research community.

For example, the Cures Acceleration Network (CAN) Act, originally championed by Senator Arlen Specter, was incorporated into the enacted law. CAN’s provisions establish a new program at NIH and empower the NIH Director to use a variety of innovative funding mechanisms to support research that bridges the gap between laboratory discoveries and tangible benefits for patients and to rapidly develop “high-need cures.” The law authorized the expenditure of $500 million for the first year; however, according to the law, CAN cannot be launched without a corresponding appropriation specifically targeted to the program. (The Senate version of the bill covering appropriations for NCI for fiscal year 2011 includes $50 million for CAN; the House has not yet introduced its version.)

Additional bills folded into the measure included the Access to Cancer Clinical Trials Act, which prohibits health insurers from denying an individual access to an “approved” clinical trial (including those funded by NIH) and requires coverage for routine patient care costs. Also included was the EARLY Act (Breast Cancer Education and Awareness Requires Learning Young), originally introduced by Representative Debbie Wasserman Schultz and Senator Amy Klobuchar, which directs NIH to fund research to develop and validate novel screening tests and methods for prevention and early detection of breast cancer in young women.

Several comparative effectiveness research provisions found their way into the health care reform legislation, as well. The law established a private nonprofit Patient Centered Outcomes Research Institute (PCORI), run by a 21-member Board of Governors, to advance and fund comparative clinical effectiveness research.

Additional Measures and Efforts

Tobacco regulation was another hot issue for the 111th Congress, as evidenced by the passage of two important tobacco bills. The Family Smoking Prevention and Tobacco Control Act (P.L. 111-31), which became law in June 2009, provided the FDA the authority to regulate tobacco products and to establish the new Center for Tobacco Products. Like many legislative measures, this bill was introduced and debated in multiple Congresses; similar legislation was introduced in March 2000 during the 106th Congress and in each subsequent Congress, eventually gaining enough traction in the current Congress to become law.

The Prevent All Cigarette Trafficking Act of 2009 (P.L. 111-154), which passed in March 2010, was designed to prevent tobacco smuggling to ensure the collection of all tobacco-related taxes and included smokeless tobacco as a regulated substance.

This Congress considered, but has not yet passed, a number of bills that were of special interest to NCI and the cancer research community. It is likely that, if these bills fail to pass in the current Congress, similar legislative measures will be re-introduced and considered in the 112th Congress.

The most high-profile of these measures was the 21st Century Cancer Access to Life-Saving Early Detection, Research and Treatment (ALERT) Act, introduced in the Senate by Senator Edward Kennedy in March 2009 and, in the House, by Representative Lois Capps. Provisions of this bill included a reauthorization of NCI and a requirement for NCI to develop a budget for the entire National Cancer Program for submission to the National Cancer Advisory Board, the President, and Congressional appropriators. The bill directs NCI to report annually on plans and progress regarding research on deadly cancers (defined as those cancers with less than 50 percent survival at 5 years), and cancers with less than 15 cases per 100,000 people or fewer than 40,000 new cases per year. The measure also requires NCI to establish an interconnected network of biorepositories and augment ongoing efforts to support the national collection of tissues for cancer research.

The 111th Congress also attempted to overhaul the Small Business Administration (SBA), which administers the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs at NIH and 10 other participating federal agencies. The SBIR and STTR programs are currently authorized under a temporary extension through January 31, 2011. Congress has extended the SBA programs through several short-term authorization measures since 2008 because House and Senate lawmakers have been unable to forge an agreement. To maintain these programs, the 112th Congress will need to pass another temporary extension and begin negotiations anew.     

The House Committee on Energy and Commerce, Subcommittee on Health, took a very active role in considering cancer legislation in this Congress. Most recently, the Subcommittee held a hearing on a series of health-related bills. The Bone Marrow Failure Disease Research and Treatment Act of 2009, the Pediatric Research Consortia Establishment Act, and the Reauthorization of Johanna’s Law were considered at the hearing, which preceded a committee bill mark-up. Before the last recess, the Energy and Commerce Committee referred these bills to the full House for a vote, and they were passed on September 30, 2010. The Senate has not acted on this collection of bills.

The 111th Congress returns to Washington this week to complete the current session before adjourning sine die. Prior to adjourning, this Congress must pass another stop-gap funding bill, or continuing resolution, to keep the federal government operating until fiscal year 2011 appropriations can be negotiated in the next Congress. The current continuing resolution expires on December 3, 2010. No date for the adjournment has been announced.

The 112th Congress will convene on January 3, 2011.

—Stacye Bruckbauer, Jeanette Contreras, and Priyanga Tuovinen

More information about NCI’s legislative activities can be found online.

New Information from SCLD

NCI’s State Cancer Legislative Database (SCLD) has published an update with newly enacted legislation and adopted resolutions from this summer.

Examples include a new law in Georgia prohibiting minors under the age of 14 from using tanning beds and requiring children ages 14–18 to have the permission of a parent; a law in Oklahoma that allows taxpayers to receive a credit on their taxes for donation to a cancer research institute; and a resolution in Indiana that charges the state’s Health Finance Commission with studying the possible outcomes of a statewide smoking ban.

The SCLD Update can be found online. Readers can subscribe to receive each new issue by e-mail as it becomes available.

Cancer.gov Update

Boletín Showcases New Design and More Features

Screenshot of the redesigned Boletín del Instituto Nacional del Cáncer

To mark its first anniversary of publication, NCI’s Spanish-language newsletter, the Boletín del Instituto Nacional del Cáncer, now offers a new graphic design and an improved navigational layout to make it easier for subscribers and readers to browse current articles and archived issues. It also features a greater number of articles to help further disseminate information about the latest research findings in cancer treatment and prevention to Spanish-speaking audiences. 

We invite you to share this newsletter with your friends, family, and colleagues. The Boletín is available on NCI’s Spanish Web site at www.cancer.gov/espanol/noticias/boletin.

The Boletín staff would also like to hear your feedback. Please share your comments as well as topics you’d like to see discussed in future issues by sending them an e-mail here.

Notes

Biospecimens from SELECT and PCPT Now Available

The Southwest Oncology Group (SWOG) is now making resources from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) available to the wider research community.

SELECT is the largest prostate cancer prevention trial ever undertaken. Funded by NCI and conducted by SWOG, a national clinical trials research network, the study opened in August 2001 and quickly exceeded its accrual goal of 35,533 men. In the fall of 2008, the trial's Data Safety and Monitoring Committee recommended that participants discontinue taking study supplements based on an interim finding of no preventive benefit.

The rich and growing biorepository from SELECT study participants includes baseline toenail clippings and baseline and post-baseline plasma, buffy coat, red blood cells, and whole blood. These samples are linked with nutritional data, adherence cohort data, and a vast clinical database from semiannual visits with each participant. The biorepository also holds prostate biopsies and surgical specimens collected from a subset of the more than 2,100 men who were diagnosed with prostate cancer during the course of the trial. DNA has been extracted and aliquotted from the serum of these prostate cancer patients and from an age- and race-matched cohort of controls.

Information and application materials for use of biorepository materials from SELECT as well as the Prostate Cancer Prevention Trial (PCPT), which randomized more than 18,800 men to receive either finasteride or a placebo for prostate cancer prevention, are now available on the SWOG Web site.

Researchers who are interested in using samples from SELECT or PCPT must submit a letter of intent to SWOG by Monday, November 29, 2010.  Full applications will be due on Monday, January 10, 2011.  

Fraumeni Recognized for Achievements by American Cancer Society, American Italian Cancer Foundation

Dr. Joseph F. Fraumeni, Jr. Dr. Joseph F. Fraumeni, Jr.

The American Cancer Society awarded the Medal of Honor to three cancer scientists on November 5 at the Society’s annual meeting in Atlanta. Dr. Joseph F. Fraumeni, Jr., the director of NCI’s Division of Cancer Epidemiology and Genetics (DCEG), received the Medal of Honor for Cancer Control. Other awardees included Dr. Patricia Ganz, University of California, Los Angeles, for achievements in clinical research and Dr. Jeffrey Pollard, Albert Einstein Cancer Center, for discoveries in basic research. The medal is the Society’s highest honor for outstanding contributions “to the fight for a world with less cancer and more birthdays.”

Dr. Fraumeni was also awarded the American Italian Cancer Foundation’s Alexander Bodini Foundation Prize for Scientific Excellence in Medicine. Dr. Fraumeni and fellow award recipient Dr. Mina J. Bissell, of the Lawrence Berkeley National Laboratory, received their awards at the Foundation’s 30th anniversary celebration in New York City on November 8.

Dr. Fraumeni is one of the world’s premier epidemiologists, specializing in research into the genetic and environmental determinants of cancer. He is best known as co-discoverer of the familial cancer syndrome named after him and his colleague Dr. Frederick P. Li (see the related article in this issue) and for a series of cancer mortality atlases that revealed distinctive patterns of cancer at the U.S. county level, enabling the detection of carcinogenic exposures in high-risk populations. These findings have resulted in the development of public health measures and policies aimed at cancer prevention and control. Dr. Fraumeni is an elected member of the National Academy of Sciences, the Institute of Medicine, and the Association of American Physicians.

NCI Recognizes Clinical Investigators with Team Leadership Award

NCI has announced the recipients of its Cancer Clinical Investigator Team Leadership Award for 2010, recognizing exceptional contributions to the advancement of new therapies through collaborative team science:

  • Dr. Rafat Abonour, Indiana University Melvin and Bren Simon Cancer Center
  • Dr. Jeffrey Bradley, Siteman Cancer Center
  • Dr. Steven Cohen, Fox Chase Cancer Center
  • Dr. Linda Duska, University of Virginia Cancer Center
  • Dr. Naomi Haas, Abramson Cancer Center
  • Dr. Elisabeth Heath, The Barbara Ann Karmanos Cancer Institute
  • Dr. Susan Kelly, The University of Texas M. D. Anderson Cancer Center
  • Dr. Smitha Krishnamurthi, Case Comprehensive Cancer Center
  • Dr. Suresh Ramalingam, Winship Cancer Institute
  • Dr. David Rizzieri, Duke Comprehensive Cancer Center
  • Dr. Cheryl Saenz, Moores Cancer Center
  • Dr. Sheri Spunt, St. Jude Children’s Research Hospital

Designed for midlevel clinical investigators, the 2-year awards provide recognition and $50,000 in funding for those who lead cancer research programs and clinical trials at NCI-designated Cancer Centers. The funding is provided to the recipient’s institution and can be applied toward the investigator’s salary, fringe benefits, and associated facilities and administrative costs. Recipients are expected to devote 10 to 15 percent of their time to the activities associated with the award.

The awards are the result of one of the recommendations of NCI’s Clinical Trials Working Group (CTWG), which was established to advise the Institute on methods to improve and enhance the publicly funded clinical trials enterprise. The broad clinical trials community, including the Clinical Trials and Translational Research Advisory Committee, provided input into the award’s development.

“NCI is pleased to be able to recognize these key clinical investigators without whom we couldn’t conduct clinical trials,” said Dr. Sheila Prindiville, director of NCI’s Coordinating Center for Clinical Trials, the office that oversees implementation of the CTWG’s recommendations. “These recipients have exceptional leadership skills in cancer clinical trial activities and have demonstrated a commitment to conducting cancer clinical trials that promise to advance care for patients.”

The awards, available to investigators at all NCI-designated Cancer Centers that participate in NCI-funded collaborative clinical trials, ultimately support a shared culture in which investigators collaborate freely across disciplines, institutions, and programs to most expeditiously advance the design and conduct of cancer clinical trials.

Learn more about how NCI is restructuring the national cancer clinical trials enterprise online.

New Brochure on Biospecimens Available

Cover of OBBR: 'Setting the Standards and Creating the Infrastructure for High Quality Biospecimens'

NCI’s Office of Biorepositories and Biospecimen Research (OBBR) issued OBBR: Setting the Standards and Creating the Infrastructure for High Quality Biospecimens, a brochure detailing the critical role of biospecimens in cancer research, OBBR’s role in setting standards to ensure high-quality biospecimens, and the benefits of a national, centralized biospecimens resource to address the current shortage of high-quality biospecimens necessary to advance medicine.

The brochure features the following topics:

  • The Impact of Biospecimens
  • The Link Between Biospecimens and Personalized Medicine
  • Setting Biospecimen Priorities
  • OBBR’s Stepwise Approach

The OBBR was established in 2005 in recognition of the critical role that biospecimens play in cancer research. The office is responsible for developing a common biorepository infrastructure that promotes resource sharing and team science to facilitate multi-institutional, high-throughput genomic and proteomic studies.

Read OBBR: Setting the Standards and Creating the Infrastructure for High Quality Biospecimens online.

New Issue of Cancer Health Disparities Newsletter Released

The latest issue of the NCI Center to Reduce Cancer Health Disparities (CRCHD) newsletter is now available online. The newest issue of the CRCHD E-Bulletin features information about the recent Geographical Management Program (GMaP) summit held in Miami, FL, as well as the Center’s participation in the 17th Annual Black America’s Dialogue on Health Conference.

In addition to information about research, training, and funding opportunities, the issue also highlights recent accomplishments of the Center’s award-winning programs, such as the Patient Navigation Research Program (PNRP).

Get more information about CRCHD and begin your free subscription to the E-Bulletin online.

NCI Exhibit Booth Wins APHA Award

NCI exhibit booth NCI exhibit booth

The NCI exhibit booth was awarded first place for outstanding exhibit design, customer service, and resources in a nonprofit category at the American Public Health Association’s 138th Public Health Expo, held November 7–10 in Denver, CO.

NCI was one of more than 700 exhibitors at this annual meeting, which was attended by approximately 13,000 health care professionals, including national and international physicians, administrators, nurses, educators, researchers, epidemiologists, and others.

Many of the free NCI publications and resources that were available at the exhibit booth can be accessed through the NCI Publications Locator. The locator allows users to print out their selections or order copies that can be mailed to them or others in need of reliable cancer information.