National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
April 20, 2010 • Volume 7 / Number 8

NEWS

Study of Tamoxifen And Raloxifene logoLong-term Follow-up Confirms Breast Cancer Risk Reduction with Raloxifene

The drugs raloxifene (Evista) and tamoxifen both substantially reduce the risk of breast cancer in women at high risk for the disease, but raloxifene causes fewer and less-severe side effects, according to the long-term results of a large breast cancer prevention trial presented yesterday at the American Association for Cancer Research (AACR) annual meeting in Washington, DC. Read more > >

COMMENTARY

Director's Update: An Unexpected Opportunity,
a Welcome Honor

The Director’s Update for this issue was taken from the remarks delivered by NCI Director Dr. John E. Niederhuber on Sunday, April 18, at the 101st Annual Meeting of the American Association for Cancer Research (AACR) in Washington, DC. Dr. Niederhuber was presented with the AACR Award for Distinguished Public Service. Read more > >

Guest Commentary by Dr. Carolyn Clancy: Focusing the Research Enterprise on the Patient

The director of AHRQ discusses how patient-centered research improves the quality of care for cancer patients Read more > >

  

IN DEPTH

UPDATES

  • FDA Update

    • Erlotinib Approved as Maintenance Therapy for Non-small Cell Lung Cancer
    • Long-term Shortage of Cancer Drug Mustargen Expected
    • Changes Announced in Approval Process for Certain Radiation Therapy Devices
  • Legislative Update

    • House Committee Convenes Hearing on Smokeless Tobacco
  • Cancer.gov Update

    • NCI Issues Updated Cancer Trends Progress Report
    • SEER Program Releases New CSR Data
    • NCI Launches “New on Cancer.gov” E-mail List
  • Notes

    • New Cancer Signatures Funding
      Opportunity Announced
    • Learn About NCI Resources and Opportunities at BIO International Convention
    • NCI and Republic of Croatia Formalize Alliance

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

AACR 101st Annual Meeting 2010 banner

Long-term Follow-up Confirms Breast Cancer Risk Reduction with Raloxifene

Study of Tamoxifen And Raloxifene logo

The drugs raloxifene (Evista) and tamoxifen both substantially reduce the risk of breast cancer in women at high risk for the disease, but raloxifene causes fewer and less-severe side effects, according to the long-term results of a large breast cancer prevention trial presented yesterday at the American Association for Cancer Research (AACR) annual meeting in Washington, DC.

The findings, from the NCI-supported Study of Tamoxifen and Raloxifene (STAR) trial, were mostly consistent with the trial’s initial results published in 2006; findings that eventually led to FDA approval of raloxifene to reduce the risk of breast cancer in postmenopausal women at increased risk. With nearly 3 more years of follow-up data on the more than 19,000 women who participated in the study, raloxifene was modestly less effective than tamoxifen at reducing the incidence of both invasive and noninvasive breast cancer, but was markedly safer and had a substantially lower risk of rare side effects, including endometrial cancer.

The updated STAR findings and the overall data on both tamoxifen and raloxifene—both of which are in a class of drugs known as selective estrogen receptor modulators, or SERMs—for breast cancer prevention are “good news for women,” said Dr. D. Lawrence Wickerham of the National Surgical Adjuvant Breast and Bowel Project, the NCI cooperative group that led the trial. “Among postmenopausal women with increased breast cancer risk, there are now two options to reduce that risk,” he said.

“I think these data are particularly good news for the primary care community,” said Dr. Judy Garber, director of the Cancer Risk and Prevention Program at the Dana-Farber Cancer Institute, during a press briefing. Particularly given their heavy use of and comfort with raloxifene to prevent and treat osteoporosis, for which it is also approved, she said, the results should “encourage primary care physicians to discuss raloxifene [for breast cancer risk reduction] more often.”

Dr. Wickerham acknowledged that the idea of taking a drug to prevent or reduce cancer risk, often called chemoprevention, has been a tough sell. “Chemoprevention is still in its infancy,” he said. “These STAR data are an important step toward bringing chemoprevention to the same level as that seen in areas like preventive cardiology,” he continued, where drug therapy is commonly used to treat heart disease precursors such as high blood pressure and high cholesterol.

Tamoxifen has been approved for breast cancer risk reduction since 1998, following the findings from the Breast Cancer Prevention Trial (BCPT), which showed a nearly 50 percent reduction in breast cancer risk among women at increased risk who took tamoxifen for 5 years compared with those who took a placebo. But tamoxifen has never caught on as a cancer prevention agent. The drug’s low uptake has often been attributed to concerns about its potential side effects, namely increased risk of endometrial cancer and dangerous blood clots.

But the potential risks of tamoxifen and raloxifene have been overstated, said Dr. Gabriel Hortobagyi, chair of the Department of Breast Medical Oncology at the University of Texas M. D. Anderson Cancer Center, during the briefing. In the BCPT, for example, even though women taking tamoxifen had a significantly increased risk of developing endometrial cancer, the risk was still less than 1 percent.

Like tamoxifen, raloxifene had been shown to decrease breast cancer risk in clinical trials. Consequently, STAR was launched to test the two drugs head-to-head in postmenopausal women who are at an elevated risk of breast cancer (based on the commonly used NCI Breast Cancer Risk Assessment Tool). On average, the women in STAR had a 15 percent increased lifetime risk of breast cancer. Participants were randomly assigned to take one of the drugs every day for 5 years.

Tools to Aid Clinician Decision Making

To help clinicians discuss breast cancer chemoprevention options with patients at the University of Pennsylvania Abramson Cancer Center, Dr. Armstrong and her colleagues are developing decision-support tools to disseminate to primary care practices. These tools will allow clinicians to take information from a patient’s health-risk appraisal, looking at factors such as family health history and reproductive risks, and link it with a decision-support tool built into the center’s electronic medical record system.

The approach is being piloted in several clinical settings and is expected to be rolled out more widely next year. The hope, said Dr. Armstrong, “is that we can get to a point where we can say that these are the women who will receive the greatest benefit from raloxifene or tamoxifen; they are way over the threshold for absolute benefit and should be offered the medication.”

If such an approach can be shown to reduce breast cancer mortality, she continued, “I think it will produce a significant impetus for health care providers to be more innovative about how we can really individualize what we do for our patients.”

When the initial STAR findings were published, with a median follow-up of 47 months, both drugs were equally effective in reducing the risk of invasive breast cancer. But the updated results show that raloxifene’s effectiveness appears to wane over time. With a median follow-up of 81 months, raloxifene was about 76 percent as effective as tamoxifen at reducing invasive breast cancer risk. For noninvasive breast cancer, which includes conditions known as ductal carcinoma in situ and lobular carcinoma in situ, tamoxifen was initially shown to be modestly more effective than raloxifene. That finding held true with the longer follow-up, but the gap narrowed, with raloxifene proving to be about 78 percent as effective as tamoxifen.

Raloxifene’s side-effect profile remained far superior, with a 45 percent reduced risk of endometrial cancer and a 25 percent lower risk of serious blood clots compared with women who took tamoxifen.

The findings add to “the evidence that supports the long-term benefits of these drugs,” said Dr. Katrina Armstrong, co-director of the Cancer Control Program at the University of Pennsylvania Abramson Cancer Center in Philadelphia. What’s needed now, Dr. Armstrong continued, “is an active effort to understand the barriers to use [of raloxifene and tamoxifen] and the implementation of clinical decision-support tools to help providers identify women who are eligible to take them and make decisions about their use.” (See the sidebar.)

In essence, she continued, it comes down to getting health care providers, namely primary care physicians, “to be comfortable doing risk stratification and prescribing preventive medications without having a biomarker like cholesterol” to guide those decisions.

“Even 12 years after tamoxifen was approved by the FDA for breast cancer risk reduction,” said Dr. Katherine Lee, co-director of the High Risk Clinic at the Cleveland Clinic Breast Center, “[many clinicians] are still very reluctant to have that conversation” with patients about taking raloxifene or tamoxifen. “I see high-risk women every day. So they will hear about chemoprevention from me; and tamoxifen and raloxifene are your current options for risk reduction,” Dr. Lee said.

Part of the reluctance, she agreed, comes back to concerns about side effects, both on the part of the clinician and the patient. But there is also another key difference between drug therapy for blood pressure or cholesterol and drug therapy for cancer prevention, she stressed: a hard endpoint that both clinicians and patients can follow. “Doctors like to follow numbers,” said Dr. Lee, who was also an investigator on the STAR trial. “With raloxifene or tamoxifen, there are no numbers. You can’t tell whether a patient is improving upon her risk. It’s far more complex.”

—Carmen Phillips

Cancer Research Highlights

MicroRNAs Linked to Trastuzumab Resistance, Brain Metastases

Researchers have tied increased levels of a microRNA (miRNA) to resistance to the targeted therapy trastuzumab (Herceptin) in women with HER2-positive breast cancer. Another research team has discovered a “signature” of miRNAs in brain metastases in patients with melanoma—a signature that is also present in the primary tumor and could identify melanoma patients at increased risk of brain metastases. The results from both studies were presented yesterday at the AACR annual meeting.

In the first study, a team from the University of Texas M. D. Anderson Cancer Center showed that HER2-positive breast cancer cell lines with experimentally increased miR-21 levels were resistant to trastuzumab compared with cell lines with lower miR-21 levels, according to Sumaiyah K. Rehman, a graduate student in the lab of Dr. Dihua Yu, who presented the findings at a press briefing. Tumor samples from patients with HER2-positive tumors that were resistant to treatment with trastuzumab had elevated miR-21 levels, Rehman explained.

In both cell lines and mouse models of breast cancer, inhibition of miR-21 levels increased the sensitivity to trastuzumab. Lower levels of miR-21 were also associated with decreased expression of the tumor-suppressor gene PTEN, which previously has been linked to trastuzumab resistance. The findings suggest that expression of miR-21 and PTEN could be “biomarkers of who may or may not respond to trastuzumab treatment,” Rehman said.

In the second study, researchers from the New York University School of Medicine analyzed samples of metastatic tumors from a cohort of 59 patients with melanoma and identified a signature of 7 miRNAs present at different levels in metastases to the brain as compared with metastases to other sites in the body. They were able to validate this signature in tumor samples from a separate cohort of 36 patients, reported lead investigator Dr. Eva Hernando. A smaller signature involving some of these same RNAs was also seen in the primary tumors of these same patients.

Cell line and mouse model studies also showed that silencing one of the miRNAs in the signature, miR-199-3p, was associated with the ability of melanoma cells to adhere to endothelial cells and migrate to the brain.

Establishing such an miRNA signature “could allow us to identify [melanoma] patients at higher risk of brain metastases,” Dr. Hernando said, meaning that these patients could be identified for intensified surveillance and be enrolled in clinical trials. Some of the implicated miRNAs also “could be targets for novel therapeutic attacks,” she said.

Diabetes Drug Metformin Prevents Lung Tumors in Mice

The diabetes drug metformin helped prevent tumors in mice that were exposed to a cancer-causing agent found in tobacco, said researchers at the AACR annual meeting. Compared with untreated mice, those that received the drug had a 53 percent reduction in lung tumor burden after exposure to the carcinogen, which is called nicotine-derived nitrosamine. The animals were treated with an oral form of metformin for 13 weeks at drug levels that would be achievable in humans, the researchers said.

“Metformin is a very interesting drug for cancer prevention,” said lead researcher Dr. Phillip A. Dennis of NCI’s Center for Cancer Research, who presented the results. “We prevented over half of the lung tumors that would have occurred from exposure to the main carcinogen in tobacco, and that’s a real and important reduction.” Dr. Dennis’ group is planning a clinical trial to test the FDA-approved drug in people at highest risk of developing lung cancer, he said.

When the researchers administered metformin to mice by injection, the drug levels were higher and the anticancer effects were even stronger—the drug reduced lung tumors by 72 percent compared with no treatment. Although this method of administration is not feasible for cancer prevention in humans, analogs of metformin that are more potent may well be more effective than the drug itself, Dr. Dennis noted. With any chemopreventive agent, however, minimal toxicity is critical, and metformin was well tolerated in the mice. In fact, the livers of the treated mice not only showed no signs of toxicity, but they actually appeared healthier than those of untreated mice.

This may be the first study to show the potential for metformin in preventing lung cancer, but preclinical studies in mouse models of breast cancer have also yielded positive results. In addition, epidemiological studies of hundreds of thousands of patients with type 2 diabetes have shown that those who take metformin have a lower risk of many types of cancer. Together, these results provide a rationale for studying the role of this drug in cancer in a variety of clinical settings, the researchers noted.

Cancer Risk Tools May Need Regular Recalibration

A new study of a statistical tool for assessing a woman’s risk of breast cancer—commonly known as the Gail model—suggests that such tools may need to be updated regularly to account for underlying trends in the population that may influence results, researchers reported online in the Journal of Clinical Oncology on April 5.

This validation study of the Gail model found that the tool underestimated the number of invasive breast cancers among women in two large population-based cohort studies. This meant that a small percentage of women did not meet the recommended threshold for using chemoprevention drugs such as tamoxifen or raloxifene, even though the women would have qualified based on a recalibrated model. The cohort studies were the NIH-AARP Diet and Health Study and the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

The researchers, led by Dr. Ruth M. Pfeiffer of NCI’s Division of Cancer Epidemiology and Genetics, attributed the underestimation primarily to differences in the breast cancer rates that were used to develop the Gail model (SEER data covering 1983 to 1987) and population rates for the time periods covered by the cohort studies used in the validation (1995 through 2003 for NIH-AARP and 1993 through 2006 for PLCO).

Breast cancer rates in the United States rose steadily in the 1990s, leveled off in about 2000, and then dropped substantially starting in 2003, when the use of menopausal hormone therapy was linked to breast cancer risk. The performance of the model improved greatly after the model was updated with population rates of invasive breast cancer in SEER data for 1995 to 2003, the researchers noted. The Gail model was well calibrated when the validation was restricted to PLCO data for the years 2003 to 2006.

Many women and health care professionals use a publicly available version of the Gail model called the Breast Cancer Risk Assessment Tool (BCRAT) to inform decisions about breast cancer prevention. This tool, which takes into account a woman’s medical and reproductive history as well as her family history of the disease, is being updated using incidence data from the SEER program and will continue to be updated regularly in the future, the researchers said. As current SEER incidence rates are similar to the original rates included in the model, the updating will not substantially affect the current BCRAT outputs but may play a more important role in the future.

“Our study shows that to ensure that a risk model is continuously useful for clinical decisions, the model has to be updated on a regular basis,” said Dr. Pfeiffer. “The take-home message is that to do good risk prediction, we have to watch out for trends in the population over time that could affect the model.”

Profiling Airway Cells May Identify Smokers at Highest Risk of Cancer

Researchers have found that improper activation of a signaling pathway in the airway cells of some smokers and former smokers is an early step in the development of lung cancer. In addition, the researchers identified a compound that inhibited the activation of this pathway, called the PI3K pathway, in some individuals with precancerous lesions. A team led by Drs. Avrum Spira of the Boston University College of Medicine and Andrea Bild of the University of Utah reported their findings in the April 7 Science Translational Medicine.

In previous work, these researchers showed that profiling the activity of 80 genes in cells from a patient’s airway could help distinguish smokers with and without lung cancer. Although these airway cells, collected during bronchoscopy, may appear normal under the microscope, they may also show abnormal patterns of gene activity associated with lung cancer. Toxins in cigarette smoke can alter the behavior of genes in cells throughout the respiratory tract, and these changes can be used for diagnostic purposes, the researchers said.

After identifying the activation of the PI3K pathway, which plays a role in a number of cancers, the researchers asked whether a drug was available to counter this effect. In a study of a small number of smokers with bronchial dysplasia, they found that treatment with myoinositol—a compound naturally found in some foods that has shown anticancer effects in mice—caused the regression of these precancerous lesions in the majority of subjects. The activity of the PI3K pathway was decreased in subjects whose lesions regressed but not in those subjects whose lesions were unchanged.

“These results suggest that deregulation of the PI3K pathway in the bronchial airway epithelium of smokers is an early, measurable, and reversible event in the development of lung cancer and that genomic profiling of these relatively accessible airway cells may enable personalized approaches to chemoprevention and therapy,” the researchers concluded.

Larger studies are needed to confirm the role of the PI3K pathway in early lung cancer and to evaluate myoinositol in humans. NCI has an ongoing phase II clinical trial of myoinositol open to participants with bronchial dysplasia. The study will assess the compound’s ability to reverse precancerous changes in the lung, measure markers of lung cancer and lung cancer risk, and establish a safety profile.

Peptide Helps Chemotherapy Penetrate Deep into Tumors

Many anticancer drugs can only penetrate a few cells away from the blood vessels that carry them into a tumor, limiting their ability to kill cells that lie deeper. In a proof-of-concept study, researchers led by Dr. Kazuki Sugahara from the University of California, Santa Barbara, showed that a tumor-penetrating peptide called iRGD, injected along with several common chemotherapies, greatly increased the amount of drug that reached tumor cells in mice. Their results were reported April 8 in Science.

iRGD binds to proteins found in the lining of tumor blood vessels but not in blood vessels found in normal tissue. Upon binding, iRGD appears to trigger an active transport process that drives drugs into the tumor tissue from the blood stream.

The researchers injected iRGD along with chemotherapy drugs in mice bearing human tumor xenografts. The combination increased accumulation of nanoparticle-embedded paclitaxel in breast cancer cells 12-fold, of doxorubicin in prostate cancer cells 7-fold, and of trastuzumab in breast cancer cells 40-fold, compared with accumulation in tumor cells when the chemotherapy drugs were given alone. These increases were observed even though iRGD was not chemically attached to the drugs.

The addition of iRGD also increased drug potency. For example, 1 mg/kg of doxorubicin plus iRGD injected intravenously was as effective at eradicating tumors in mice as 3 mg/kg doxorubicin given without iRGD, and it did not increase toxicity.

“Coadministration of iRGD may be a [way] to enhance the efficacy of anticancer drugs while reducing their side effects, a primary goal of cancer therapy research,” concluded the authors. They caution that iRGD has not yet been tested for safety or efficacy in people.

Also in the Journals: Treating Childhood Cancers—How to Build on Success

A new analysis of childhood cancer statistics estimates that 38,000 cancer-related deaths in children were averted in the United States between 1975 and 2006, largely thanks to new drugs, improved treatment strategies, and past investments in clinical trials. But clinical research on these diseases is at a crossroads, the study authors cautioned in the April 19 Journal of Clinical Oncology. The era of steady improvements in outcomes by optimizing the delivery of conventional therapies is coming to a close, they wrote, while the era of targeted therapeutics is just beginning.

“Our progress has slowed, and now we need a deeper understanding of the biology of childhood cancers and the genes and pathways that drive them,” said lead author Dr. Malcolm Smith of NCI’s Cancer Therapy Evaluation Program in a statement. “With this understanding, we can identify susceptibilities that can be therapeutically exploited so that we continue moving forward toward the goal of curative therapy for every child diagnosed with cancer.”

The promise of this strategy has been demonstrated by early results such as those from the Childhood Cancer TARGET Initiative, an NCI-supported project that brings together investigators with expertise on childhood cancers and genome analysis, the authors noted.

Director's Update

An Unexpected Opportunity, a Welcome Honor

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

During Sunday’s opening ceremonies for the 101st annual meeting of the American Association for Cancer Research (AACR), NCI Director Dr. John E. Niederhuber received the AACR Award for Distinguished Public Service. In presenting the citation, the organization’s 2009–2010 president, Dr. Tyler Jacks, director of the David H. Koch Institute for Integrative Cancer Research and the David H. Koch Professor of Biology at the Massachusetts Institute of Technology, lauded Dr. Niederhuber for being a “nationally renowned surgeon and researcher,” who has “dedicated his career to the treatment and study of cancer.” The comments below are taken from Dr. Niederhuber’s acceptance remarks.

Thank you, Tyler, for that very kind tribute, and also for your excellent leadership of AACR during your presidential year. Dr. Margaret Foti [AACR Chief Executive Officer], I would also like to thank you for your tireless and visionary guidance of this great society as its executive director, and, of course, I am immensely grateful that my colleagues on the AACR board of directors have thought me worthy of this honor, which I am most humbled to accept.

It has been a truly unexpected opportunity and a great honor to have been chosen to lead the National Cancer Institute and the National Cancer Program. When I first came to NCI in the summer of 2005, I promised to stay a year to help with a couple of challenges. That plan quickly—and quite unexpectedly—changed, and within 2 months, I was responsible for running the largest institute at NIH. I am grateful that my former colleague from Johns Hopkins University and dear friend Dr. Elias Zerhouni, the NIH director, had the confidence in me to push for my permanent appointment as NCI director, which I think is, by far, the best and most important job in government. These 5 years have been a wonderful experience and, as I said, a very humbling honor.

There is, however, one person who is not overly impressed by this honor: my 102-year-old mother. As she reiterated on the phone last night, my mother has never quite accepted that I no longer care for patients or perform surgery.

I have been blessed in my life beyond words. For reasons I will never understand, I was given an opportunity to study medicine, to teach students of medicine, and train surgeons. I have had my own laboratory and, throughout my career, been part of both the basic science faculty and the clinical faculty. But above all, I have been entrusted with the care of some truly remarkable human beings. I cannot, in any way, imagine a more personally rewarding life, and for that, I will be forever grateful.

So I accept this award on behalf of my colleagues at the National Cancer Institute. You are the hardest working group of selfless professionals I have ever been so fortunate to lead. You have taught me much and inspired me greatly.

And finally, I would not be standing here before you this morning were it not for the many, many talented students and fellows who worked in my labs over the years; the many outstanding trainees in surgery, a number of whom are now leading their own departments and programs across the country; and the patients with cancer who had the confidence to place their care in my hands. It is my patients who have taught me the most important lessons of humility, the value of service, and the strength of perseverance.

Thank you again for this great honor. I shall cherish it always, and I will never forget this moment.

Dr. John E. Niederhuber
Director, National Cancer Institute

Guest Commentary by Dr. Carolyn Clancy

Focusing the Research Enterprise on the Patient

Dr. Carolyn Clancy Dr. Carolyn Clancy

Let’s start with a case study. We have a patient with cancer, a 63-year-old woman named JG, who is treated at a renowned cancer center for stage III melanoma. She has been in good health until her cancer diagnosis, and she responds well to treatment. For 6 years following initial treatment, JG thinks she is cancer free—until she is hospitalized for fatigue and diffuse back pain and tests reveal extensive metastases.

By now, of course, JG isn’t an otherwise spry 63-year-old fighting cancer. She’s 70, she has become the primary guardian of two grandchildren with special challenges, she has already been through one debilitating course of treatment, and the recurrence hasn’t been caught in time. The prognosis is grim. She is transferred to a rehabilitation facility and given palliative care, but the pain only gets worse. Two weeks later, she’s back at the cancer center, this time with cancer cells filling parts of her lungs. Within 48 hours, JG dies.

At the outset, we can agree on three things. We know that JG received excellent treatment initially. We know that JG suffered unnecessarily at death. And, we know that something happened in between treatment and death that shouldn’t have happened.

JG’s case demonstrates that health care quality is not a fixed point on a map. Quality doesn’t happen once; it happens, or fails to happen, over long periods of time, in patient interactions with multiple clinicians, and usually at multiple locations. If at any point the ball is dropped—if a tumor isn’t caught when it should be; if a diagnostic test result is misinterpreted; if a patient does not receive treatment in a timely manner; if she suffers needlessly at death—then the overall quality of care has been poor, even if many of the individual instances of care were very good.

That is the essence of patient-centered care: it is of high quality only when the ultimate needs of the patient are met.

Unfortunately, statistics tracked by my agency, the Agency for Healthcare Research and Quality (AHRQ), indicate that the quality of cancer care in the United States could be much better. Take for example colorectal cancer, which kills nearly 50,000 people a year in the United States, second only to lung cancer. As this publication recently reported, screening is underused despite clinical guidelines. According to the 2008 National Healthcare Quality Report, only 55 percent of Americans age 50 and older receive regular screenings for colorectal cancer, and geographic disparities for colonoscopy and sigmoidoscopy are widespread.

But we are doing something about it. AHRQ is the lead federal agency on a type of patient-centered health research known as comparative effectiveness research, which compares different diagnostic tests and interventions to gauge which works best for whom, and under which circumstances. AHRQ has been conducting this research since 2005 under its Effective Health Care Program, and—together with our federal partners, NIH, and the Secretary of Health and Human Services—we are advancing this research with an unprecedented federal investment under the American Recovery and Reinvestment Act of 2009.

Comparative effectiveness research is built on the understanding that in health care, there is really only one relevant question: not “What is the right treatment?” but “What is the right treatment for me?” This research provides tools so that patients can work with their physicians to determine their own best course of treatment. Accordingly, the Effective Health Care Program produces summary guides based on its comparative effectiveness reviews, tailored for consumers and clinicians. These summary guides are important to patient-centered care because they put the results of research directly in the hands of those who most need the results.

Cancer is one of the Effective Health Care Program’s 14 priority areas, and the program has recently produced several reports on cancer, including a technical brief on particle beam radiation therapy, a review comparing tamoxifen and other medicines to reduce the risk of primary breast cancer in women, a review comparing core needle biopsy to surgical incision biopsy for diagnosing breast lesions, and a review comparing the effectiveness of therapies for clinically localized prostate cancer.

The story of JG hits very close to home for me, because she’s not an anonymous case study—she was my Aunt Jeanne. Would any of these reports, or any currently under development, have helped her? That’s difficult to say. Her story has elements of suboptimal quality of care and poor patient adherence, but it also demonstrates just how challenging a disease cancer is. We have high hopes for the patient-centered research that is being done today, but we should not believe that this research represents a magic bullet for health care.

Instead, this research will become a powerful tool that we can use to help transform our system of care. It is my expectation that these reports and reports like them ultimately will lead to a health care system with patients at the center.

Dr. Carolyn M. Clancy
Director, Agency for Healthcare Research and Quality

Special Report

Trial Makes Push Toward More Individualized Lung Cancer Therapy

Preliminary findings from the first clinical trial in lung cancer to use molecular analysis of tumor biopsy samples and an “adaptive” design to direct patients to a specific targeted therapy were presented at the AACR annual meeting in Washington, DC. In the study, dubbed BATTLE, patients had their tumor samples tested for specific biomarkers and were enrolled into one of four treatment arms, each one testing a different targeted therapy, based on that analysis. (See the box below.)

The first 97 patients to enroll in BATTLE were randomly assigned to one of the four treatment arms as would traditionally be done. After that point, new patients were assigned to one of the arms based on a statistical model called an adaptive Bayesian model. In addition to using the result of the biomarker analysis, the model made the assignment based on findings from patients who had already undergone treatment, which, as the trial proceeds, are fed back into the model.

'Our hope is that this type of study will streamline development because it will identify efficacy signals earlier' - Dr. Edward Kim

“Our hope is that this type of study will streamline development because it will identify efficacy signals earlier,” said Dr. Edward Kim from the University of Texas M. D. Anderson Cancer Center, who presented the results on Sunday. “So instead of doing large phase III trials where we’re looking for a 1.5-month improvement in overall survival, we can find a marker that represents a strong signal for the drug and makes the overall efficacy much better” in a smaller, more tightly defined trial population.

But, Dr. Kim acknowledged, BATTLE, which was designed in 2004, is only a beginning. “This type of trial model is highly dependent on having good biomarkers and good treatments,” he said, both of which are severely lacking for patients with advanced disease.

Like BATTLE, the recently launched I-SPY2 trial for breast cancer has an adaptive design statistical model. But I-SPY2 involves a healthier population of patients and is studying the delivery of treatments prior to surgery.

BATTLE’s Drugs and Markers

Patient tumor samples in BATTLE, which were acquired fresh after enrollment, were analyzed for the presence of 11 different biomarkers, including mutations in genes such as EGFR and KRAS, excessive copies (or amplification) of Cyclin D1, or the expression of proteins such VEGF.

The four treatments used in the trial were erlotinib (Tarceva), sorafenib (Nexavar), vandetanib  (Zactima), or erlotinib and bexarotene (Targretin).

More than 300 patients were enrolled in BATTLE. The results presented at the AACR meeting were based on data from 244 patients. The trial’s primary endpoint was control of patients’ disease at 8 weeks. While overall survival for patients in the trial was 9 months, patients whose disease was well controlled at 8 weeks had a median overall survival of 11 months, compared with 7.5 months for patients whose disease was not well controlled at that point. No progression-free or overall survival data for each of the four trial arms are yet available.

Interpreting the limited findings from BATTLE is difficult, said Dr. Giuseppe Giaccone, chief of the Medical Oncology Branch and head of the Thoracic Oncology Section in NCI’s Center for Cancer Research. That is due in large part because of some significant limitations in the study’s design. For example, Dr. Giaccone explained, 8-week disease control is not a validated endpoint in lung cancer clinical trials. And the study lacked a control arm, making it difficult to judge the efficacy of the individual drugs, of which only erlotinib (Tarceva) is approved by the FDA for treating lung cancer.

During the plenary session presentation, Dr. Paul Bunn, director of the University of Colorado Cancer Center, lauded the ability to conduct such a complex trial but also touched on some concerns, including the rationale of using erlotinib in combination with bexarotene (Targretin), which is approved to treat cutaneous T-cell lymphoma but has not shown activity in lung cancer.

While it is a phase II study and has its limitations, Dr. Kim stressed that BATTLE underscores the importance of getting adequate tissue samples from patients with non-small cell lung cancer (NSCLC). Currently, Dr. Kim said, tumor samples are available for only 20 to 30 percent of patients.

Uniformly obtaining suitable tissue samples will greatly aid research, Dr. Kim noted. And as studies emerge pointing to biomarkers that may predict response to approved and investigational treatments—such as EGFR mutations for erlotinib and the presence of the EML4-ALK gene fusion for investigational ALK inhibitors—samples will be available to test for those markers and offer patients a potentially effective treatment.

Based in part on their experience with BATTLE, M. D. Anderson Cancer Center researchers will publish papers in the future that identify “good targets” for metastatic or primary tumor sites “to optimize the amount of tissue you can get from a biopsy,” Dr. Kim said.

Two similar adaptive-design trials, BATTLE 2 and BATTLE 3, are already moving ahead, Dr. Kim said. BATTLE 2 will have a similar patient population to BATTLE, but with a number of modifications to the design, including less reliance on prespecified biomarkers. BATTLE 3 will involve patients undergoing initial therapy for advanced NSCLC.

Carmen Phillips

Spotlight

Genome Study of Aggressive Breast Cancer Yields Clues to Metastasis

To study how cancer cells change as the disease progresses, researchers have carried out a genome analysis of four DNA samples from a woman with breast cancer whose disease spread to her brain. In addition to the primary breast and metastatic brain tumors, the researchers used the patient’s normal blood cells and a tumor grown in a mouse from a sample of the original tumor (a xenograft).

A four-way comparison of the sequence and genome structure data has opened a window into the metastatic process in a single patient. The metastatic and xenograft tumors (i.e., the secondary tumors) both appeared to arise from a minority of cells in the patient’s breast tumor, researchers from the Washington University School of Medicine in St. Louis and their colleagues reported in the April 15 Nature.

The patient was a 44-year-old African American woman with inflammatory breast cancer that had the hallmarks of the basal-like subtype of breast cancer. These are aggressive tumors that disproportionately affect younger women and African Americans. Despite chemotherapy and radiation therapy, the patient died within a year of diagnosis, and her case was not unusual, the researchers noted.

To investigate the genetic changes underlying this metastatic process, a team led by Washington University’s Drs. Li Ding and Matthew Ellis profiled genetic mutations, structural changes, and differences in the number of gene copies in the four samples. Their analysis revealed 48 genetic mutations that were common to all three tumors (primary, metastatic, and xenograft), a number of structural alterations, including some large deletions, and about 7 translocations that occurred between chromosomes in the primary tumor alone, confirming previous reports that basal-like breast cancers have unstable genomes.

While additional genetic mutations and other changes did occur over the clinical course of the disease, most of the original mutations and structural variants in the breast tumor were present in the metastatic brain tumors and in the xenograft.

Tour de Force

“This study is a true tour de force in genomics,” said Dr. Patricia Steeg, who heads the Women’s Cancers Section in NCI’s Laboratory of Molecular Pharmacology and was not involved in the study. “Wouldn’t it be fascinating to see how a liver metastasis varies from a brain metastasis? Or how two metastases from the same organ do or don’t vary?”

'This study is a true tour de force in genomics.' - Dr. Patricia Steeg

This was only the second study to use whole-genome sequencing to compare a primary tumor and metastasis from the same patient. In the first study, published last year, the majority of mutations found in the metastasis had not been present in the primary tumor. But there were fundamental differences between the studies, including the fact that the metastatic process evolved over 9 years in the first study compared with less than a year in the current report.

“This emerging literature says that metastases are not identical to primary tumors,” noted Dr. Steeg, who is also president of the Metastasis Research Society. “They may be similar in many respects, but important differences remain. For most cancers, we are trying to develop treatments for metastatic disease, and I hope the new data will prompt more translational researchers to use metastatic models for experimental therapeutics.”

Because basal-like breast cancers have unstable genomes, researchers have wondered whether the deadly metastatic process is driven by mutations that occur after the tumor cells arrive at the distant site, or whether the primary tumor produces cells with the full complement of mutations required for metastatic growth. The findings support the latter view, but the researchers stress that more comparisons are needed to confirm the results.

Some of those studies are underway, according to Dr. Elaine Mardis, co-director of The Genome Center at Washington University and the study’s senior author. Her team has obtained DNA samples from other patients with basal breast cancers that have spread to various parts of the body.

“Sequencing more samples could help us understand the genetic landscape of the basal-subtype tumor and also to identify commonly mutated genes,” said Dr. Mardis. “These genes would be of interest for developing targeted therapies for treating these very aggressive tumors.”

Basal breast cancers are heterogeneous, noted Dr. Steeg, and the patient in this study represents one rare form.

A Remarkable Puzzle

In an accompanying editorial, Dr. Joe Gray of the Lawrence Berkeley National Laboratory noted that the researchers obtained a remarkable result when they tested the prevalence of the mutant DNA sequences in the tumors. Because the next-generation DNA sequencing machines in the study measure mutations in individual strands of DNA, the authors were able to calculate the prevalence of mutations as a fraction of the sequences at each genomic region carrying a mutation.

This analysis revealed that 16 mutations were present in almost every metastatic cancer cell in the patient and in almost every xenograft tumor cell in the mouse, although the mutations were found in a much smaller proportion of cells in the primary tumor. This finding “suggests that similar evolutionary pressures are at work on these cells in both environments,” Dr. Gray wrote.

The breast cancer cells used to seed the mouse tumor were collected before the patient received any therapy and therefore had not been affected by exposure to therapies. “The natural histories of the xenograft tumor and the metastasis were obviously quite different, yet in both tumors we see these same 16 genes rising to prevalence,” said Dr. Mardis. “This is a very interesting finding.”

The similarity of the brain metastasis specimen and the xenograft is a puzzle, said Dr. Steeg. “I am not sure, however, that these data are representative of long-term cell lines, which are the mainstay of our experimental therapeutics research,” she added. 

Dr. Gray noted that further work is needed to determine which genetic changes in the tumors are driving the disease and which ones are merely present.

Unexpected Bonus

This study had several firsts—the first published genome of an African American and the first basal-like breast cancer genome sequence. But it will likely be one of the last genome studies by these authors to describe a single patient.

“We are rapidly transitioning from doing tumor-normal genome comparisons, and even quartet studies like this one, to multi-tumor studies and analyses,” Dr. Mardis said. The group has sequenced 50 genomes from patients with acute myeloid leukemia and a similar number of breast cancers. They are also sequencing the genomes of 600 patients with pediatric cancers, in collaboration with St. Jude Children’s Research Hospital.

An unexpected bonus from this research was considerable information about the genetics of the immune-deficient mice used in the study, which came about because mouse cells were inadvertently sequenced along with the human cells from the xenograft tumors. The researchers are planning to make this information publicly available.

—Edward R. Winstead

Featured Clinical Trial

Pioglitazone for Oral Premalignant Lesions

Name of the Trial
Phase IIB Randomized, Placebo-Controlled Trial of Pioglitazone for Oral Premalignant Lesions: An Inter-Consortium Collaborative Study (2009-0339).  See the protocol summary.

Dr. Jay Boyle Dr. Jay Boyle
Dr. Frank Ondrey Dr. Frank Ondrey

Principal Investigators
Dr. Jay Boyle, Memorial Sloan-Kettering Cancer Center, and Dr. Frank Ondrey, University of Minnesota

Why This Trial Is Important
Oral cancer is often preceded by persistent sores or white patches in the mouth known as oral leukoplakia. However, not all leukoplakia lesions progress to cancer. Although the exact causes of oral leukoplakia are unknown, they are associated with tobacco use, long-term alcohol consumption, and chronic irritation of the mucous membranes in the mouth.

Researchers are investigating several different interventions to try to stop oral leukoplakia from progressing to cancer. One promising intervention is pioglitazone (Actos), a drug that is commonly used to treat type II diabetes. In an earlier small phase II study, pioglitazone showed activity against oral leukoplakia.

“Pioglitazone acts by activating nuclear receptors and altering the expression of genes that may affect key processes in carcinogenesis, such as cell growth, cell differentiation, and cell death through apoptosis,” said Dr. Boyle.

In this trial, patients with oral leukoplakia will be randomly assigned to receive either pioglitazone or placebo pills daily for 6 months. Doctors will assess the ability of pioglitazone to shrink or eliminate leukoplakia lesions in the mouth and reduce the degree of dysplasia or hyperplasia associated with them.

“In our previous study, we found that 3 months of treatment with pioglitazone did a good job of eliminating the lesions, but the dysplasia associated with them often didn’t change much,” said Dr. Ondrey. “We felt the study provided strong evidence that pioglitazone may be effective as a chemoprevention drug, so our next step is this randomized, placebo-controlled study that will treat patients for 6 months instead of 3 months in hopes of further reducing both the leukoplakia lesions as well as the dysplasia.”

“Pioglitazone is approved by the FDA and widely used as a diabetes drug, and it has an excellent safety profile,” added Dr. Boyle. “Given the good preliminary evidence that it might be useful as a chemopreventive and its safety record, it makes sense to further explore its use in patients with these lesions.”

For More Information
See the lists of eligibility 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/ft-all-featured-trials.

Community Update

IOM Committee Recommends Overhaul of NCI Clinical Trials Cooperative Group Program

Cover of the IoM Report, 'A National Cancer Clinical Trials System for the 21st Century'

A special Institute of Medicine (IOM) committee has recommended substantial restructuring and increased funding of NCI’s in a report issued April 15 titled A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program.

The IOM committee’s report and analysis, which was requested by NCI Director Dr. John E. Niederhuber, lauded the cooperative groups’ substantial contributions in past years to landmark research for improving cancer care. However, Dr. John Mendelsohn, IOM committee chairman and president of the University of Texas M. D. Anderson Cancer Center, also cautioned that “the NCI Cooperative Group Program is falling short of its full potential to improve the quality of care that cancer patients receive. An accumulation of problems is hampering progress just at a time when new knowledge about the genetic and molecular underpinnings of cancer has created opportunities for designing trials with new, targeted anticancer agents.”

The IOM committee issued recommendations based on four broad goals for improving the cooperative group clinical trials process:

  • Improve the efficiency and reduce average time for the design and launch of innovative clinical trials by con­solidating functions, committees, and cooperative groups; streamlining oversight processes; facilitating collaboration; and streamlining and stan­dardizing data collection and analysis.
  • Incorporate innovation in science and trial design, for example, in studies identifying biomarkers that can predict therapeutic response.
  • Adequately support those clinical trials that have the greatest possibility of improving survival and the quality of life for cancer patients, and increase the rate of clinical trial completion and publication.
  • Incentivize the participation of patients and physicians in clinical trials by providing adequate funds to cover the costs of research by reimbursing the costs of standard patient care during the trial.

In an independent survey of NCI cooperative group members, conducted by the American Society of Clinical Oncology (ASCO) and published in the May issue of the Journal of Oncology Practice, 33 percent of respondents were planning to limit their participation in NCI-funded cooperative trials and another 9 percent were considering limiting participation. A majority (75 percent) of these cooperative group respondents cited inadequate NCI reimbursement as the reason for limiting involvement in such studies. NCI’s per-patient case reimbursement of $2,000 for cooperative group studies has not changed in 10 years and falls short of the estimated $5,000 to $6,000 typically spent per patient enrolled, the ASCO authors wrote.

Dr. Mendelsohn noted that the IOM committee also endorsed the recommendations recently made by NCI’s Operational Efficiency Working Group (OEWG), which aim to achieve similar goals for improving the cooperative group program and cancer clinical trials in general. Those recommendations were highlighted by Dr. James H. Doroshow, director of NCI’s Division of Cancer Treatment and Diagnosis in an April 6 Guest Director's Update for the NCI Cancer Bulletin.

Responding to the IOM report’s release, Dr. Doroshow expressed thanks to the IOM committee for their efforts and “complete endorsement” of the OEWG report. “We will carefully review the IOM report and equally carefully consider how we will follow up on its recommendations,” he added. “Our hope is that this report will complement NCI’s ongoing efforts to improve the clinical trials system, as we continue working to implement the recommendations of our Clinical Trials Working Group’s 2005 report.”

The IOM report helps “reinforce the notion that in an era of molecular oncology the clinical trials process must change,” Dr. Doroshow added. “The costs—in dollars and time—to bring a new drug to market are unsustainable. Moreover, cancer clinical trials of the future will require the testing of multiple agents against multiple disease targets. Creating a cancer clinical trials system capable of testing multiple hypotheses faster, with less cost and greater efficiency, is and must remain one of NCI’s highest priorities.”

Bill Robinson

FDA Update

Erlotinib Approved as Maintenance Therapy for Non-small Cell Lung Cancer

Last week, the FDA approved erlotinib (Tarceva) to prevent the recurrence of non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after receiving initial treatment with platinum-based chemotherapy. Maintenance therapy is a new approach intended to capitalize immediately on a drug’s initial chemotherapeutic success rather than waiting for cancer to return or progress, which can be especially problematic in lung cancer.
 
This approval is based on the results of the SATURN trial, an international phase III clinical trial of approximately 889 patients with advanced NSCLC. Patients in the trial were given four cycles of first-line platinum-based chemotherapy; those whose cancer did not progress were then randomized to receive erlotinib or a placebo. Patients who received erlotinib had a median 1.2-week improvement in progression-free survival (12.3 weeks versus 11.1 weeks) and a median 1-month improvement in overall survival (12 months versus 11 months).

Erlotinib, which targets the EGFR pathway, was originally approved in 2004 to treat locally advanced or metastatic NSCLC that had spread after at least one course of chemotherapy. The FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 12-1 against this Supplemental New Drug Approval in December 2009.

The acting chair of the ODAC panel in December 2009, Dr. Wyndham Wilson of NCI’s Center for Cancer Research, explained that when a drug such as erlotinib has been shown to be effective in patients whose cancer progresses, it is incumbent on researchers to show in a clinical trial that there is an independent advantage to using the drug in the earlier, maintenance setting.

“If control patients are not crossed over to erlotinib when their disease begins to progress,” Dr. Wilson said, “any benefit observed in the maintenance arm may simply be due to drug access, which is not available to the control patients. Importantly,” he continued, “if the drug is not significantly more beneficial when given as maintenance therapy versus at the time of disease progression, many patients in the maintenance arm will be unnecessarily overtreated and risk potentially serious side effects, such as blood clots, and the inconvenience of treatment.”

Long-term Shortage of Cancer Drug Mustargen Expected

The FDA has issued a drug shortage warning for mechlorethamine HCl (Mustargen), which is approved for the treatment of advanced Hodgkin disease and a number of hematologic and other cancers. According to Lundbeck, Inc., the sole manufacturer, the drug will be in short supply for up to a year because of manufacturing problems.

A limited supply will become available in mid- to late-April, with preference given to patients who are currently receiving the drug for therapy. Pharmacies and physicians are advised to contact their distributor or wholesaler in order to meet the needs of those patients, and then to develop an orderly transition to alternative therapies.

It is the FDA’s policy to help prevent or alleviate shortages of medically necessary drugs that could significantly impact public health. The agency “has searched but is unaware of any other supplies of mechlorethamine HCl available from any other sources at this time,” and advised that alternative treatment plans should be made for patients who have been recently prescribed Mustargen.

Changes Announced in Approval Process for Certain Radiation Therapy Devices

On April 8, the FDA sent a letter to manufacturers of linear accelerators (machines that create radiation used in cancer therapy), radiation therapy treatment planning systems, and ancillary devices with a notification that their products may no longer be eligible for third-party review as part of the premarket 510(k) approval process. In the 510(k) approval process, manufacturers must show that their new product is at least as safe and effective as a similar, legally marketed device.

Third-party 510(k) review for biomedical devices was introduced as a money-saving strategy in the FDA Modernization Act of 1997, and it allows device manufacturers to have accredited, non-federal organizations review their approval applications, leaving only the final decision to the FDA. However, the process has recently come under scrutiny for potentially being too lenient.

The FDA “is taking several steps to improve the safety and safe use of certain radiation therapy devices,” including restrictions on third-party review, wrote Dr. Jeffrey Shuren, director of the FDA’s Center for Devices and Radiological Health, in the April 8 letter. Between December 31, 1999, and February 18, 2010, the FDA received 1,182 Medical Device Reports for radiation therapy devices that “revealed device problems that appear to be the result of faulty design or use error that could be mitigated by the incorporation of additional safeguards,” wrote Dr. Shuren.

Linear accelerators accounted for 74 percent of these error reports, radiation therapy treatment planning systems accounted for 19 percent, and ancillary devices, including proton therapy machines and radiation therapy simulators, accounted for 7 percent. Software problems triggered 362 of the error reports overall.

The FDA is planning to hold a public workshop on radiation therapy treatment planning, medical linear accelerators, and ancillary devices. Topics for discussion will include new safeguards; changes in premarket device testing to provide appropriate assurances of safety and effectiveness (particularly for software); and premarket review for modifications to software. The date and time of the workshop will be announced in the Federal Register.

Legislative Update

House Committee Convenes Hearing on Smokeless Tobacco

The House of Representatives Committee on Energy and Commerce, Subcommittee on Health, held a hearing on April 14: “Smokeless Tobacco: Impact on the Health of Our Nation's Youth and Use in Major League Baseball.” NCI’s Deputy Director of the Division of Cancer Control and Population Sciences Dr. Deborah Winn testified before the committee, as did Dr. Terry Pechacek, associate director for science in the CDC’s Office on Smoking and Health.

The full panel of witnesses included representatives of Major League Baseball (MLB) and the MLB Players Association (MLBPA); Dr. Greg Connolly, a dentist and Harvard professor who has conducted research on smokeless tobacco for more than 20 years; Gruen Von Behrens, an oral cancer survivor and tobacco prevention advocate; and baseball legend Joe Garagiola, Sr., who continues to work as an MLB announcer and is a vocal advocate for ridding MLB of smokeless tobacco.

Dr. Winn’s testimony recognized smokeless tobacco, which includes snuff and chewing tobacco, as an established cause of oral, pharyngeal, pancreatic, and esophageal cancers, and stressed that there is no safe level of tobacco use. She also addressed questions from members of the committee regarding MLB players using smokeless tobacco on the field, and therefore on television. Media depictions of tobacco use have been shown to contribute to an increase in youth tobacco use, explained Dr. Winn. NCI’s “Monograph 19: The Role of the Media in Promoting and Reducing Tobacco Use” provides additional information on this topic.

Dr. Pechacek provided an overview of current trends in smokeless tobacco use, revealing that new CDC survey data indicate that after years of decline, smokeless tobacco use is actually increasing now among males in grades 9 through 12. These latest data will be available this summer, when the CDC releases the 2009 Youth Risk Behavior Surveillance System results. These findings add to existing data, which indicate increases in smokeless tobacco use among white and Hispanic young men (particularly those between age 18 and 25) between 2003 and 2008.

Throughout the hearing, committee members and witnesses discussed Minor League Baseball’s policy prohibiting smokeless tobacco use on the field and in the clubhouse. Committee chairman Rep. Henry Waxman (D-CA) and subcommittee chairman Rep. Frank Pallone (D-NJ) encouraged MLB and the MLBPA to discuss and adopt this policy during their upcoming collective bargaining process.

NCI currently funds six grants addressing smokeless tobacco via its RFA, “Measures and Determinants of Smokeless Tobacco Use, Prevention, and Cessation.” More information about these funding opportunities can be found at http://cancercontrol.cancer.gov/tcrb/research_topic-smokeless.html.

More information on the hearing, including a full list of witnesses, can be found on the committee Web site.

For more information about this and other NCI congressional activity, visit the NCI Office of Government and Congressional Relations Web site.

Cancer.gov Update

NCI Issues Updated Cancer Trends Progress Report

Screenshot of Cancer Trends Progress Report Web site

NCI recently released the Cancer Trends Progress Report: 2009/2010 Update. The online report summarizes the nation’s progress against cancer, from prevention through end of life, in relation to the Department of Health and Human Services’ Healthy People targets. This year’s update expands the focus of the report to include nine new measures; a reporting of health differences and health inequalities across measures, where they exist; and a new summary measure of the most recent trends (Average Annual Percent Change).

Report features include:

  • Quick tutorial to ease navigation and downloading of materials within the report
  • Updated “Trends-at-a-Glance” snapshot
  • Links to NCI's State Cancer Profiles’ state- and county-level data
  • Links to colorectal cancer mortality projections
  • Links to Healthy People 2010 materials
  • Data, graphs, and slides that are easy to download
  • Custom report features
  • Open text search capability
  • Full accessibility for persons with disabilities

New measures include:

  • Medicaid coverage of tobacco dependence treatments
  • Tobacco company marketing expenditures
  • Treatment for prostate, kidney, lung, ovarian, and bladder cancer
  • Cost of cancer care (expanded)
  • Cancer survivors and smoking

The Cancer Trends Progress Report, first issued in 2001, is updated bi-annually and when new data become available. The report offers updated national trends data in a user-friendly format and is intended for policy makers, researchers, clinicians, and public health service providers.

SEER Program Releases New CSR Data

On April 15, NCI’s Surveillance Research Program (SRP) released the SEER Cancer Statistics Review (CSR), 1975-2007. The updated SEER CSR presents the most recent cancer incidence, survival, prevalence, and lifetime risk statistics. National cancer mortality statistics will be added to the report as soon as they are available. All material in the SEER CSR report is in the public domain and may be reproduced or copied without permission. However, a citation of it as the original source is appreciated.

In addition to the SEER CSR, SRP has posted the following materials online:

The latest SEER data were also released through SEER*Stat, statistical software that provides a mechanism for analyzing SEER and other cancer-related databases.

NCI Launches “New on Cancer.gov” E-mail List

NCI’s Office of Communications and Education has launched a new e-mail list to inform Cancer.gov users when new content is added to the Web site. Subscribers will receive an e-mail update whenever new clinical trial results, featured clinical trials, drug information summaries, FDA drug approval notices, fact sheets, patient education publications, or other content pieces are posted. The e-mail list is hosted by the NIH Listserv, which allows users the freedom to easily subscribe, unsubscribe, or change their subscription settings, such as choosing to receive a digest version instead of individual e-mails each time new content is added (on average two to three times a week).

There are two ways to subscribe to the new listserv, NEW_ON_CANCERGOV-L:

  1. To subscribe via e-mail, send a message to LISTSERV@list.nih.gov with the following text in the body of the message (using your own first and last name in place of the italicized text): SUBSCRIBE NEW_ON_CANCERGOV-L firstname lastname. You will receive a confirmation e-mail. Click the link in the e-mail to confirm registration.
  1. To subscribe online, go to http://list.nih.gov/ and click on “Login.” Enter your e-mail address and create or enter your existing NIH Listserv password as prompted. You will receive a confirmation e-mail. Click the link in the e-mail to confirm registration. Once you are registered, find the NEW_ON_CANCERGOV-L list using the alphabetic list or enter “cancer” in the search box. Choose “Subscribe/Unsubscribe” from the options on the right side of the page, enter your name and email address, and click the “Subscribe” button. You will receive a confirmation e-mail; click the link in the e-mail to confirm registration.

Notes

New Cancer Signatures Funding Opportunity Announced

NCI is seeking new projects for its Strategic Partnering to Evaluate Cancer Signatures (SPECS) program. The SPECS initiative, a multidisciplinary program, supports large collaborative research groups that are exploring how information derived from comprehensive molecular analyses can be used to improve patient care and patient outcomes.

The program announcement will be open from 2010–2012, with application submission deadlines of June 15 each year. Partnerships may include industry, hospitals, and academic, government, and other entities.

Questions should be directed to Dr. Tracy Lively (livelyt@mail.nih.gov) or Dr. James V. Tricoli (tricolij@mail.nih.gov). Applicants anticipating direct costs in excess of $500,000 in any year of the project must contact Dr. Lively by May 1, 2010.

Learn About NCI Resources and Opportunities at BIO International Convention

BIO International Convention tile

NCI experts will be present at the 2010 BIO International Convention, which will take place May 3–6 in Chicago, IL. While at the convention, visit NCI’s exhibit at booth #1221 to engage with NCI experts and get the latest information on the resources, initiatives, and partnerships NCI has to help advance promising cancer research discoveries into new cancer therapies.

NCI and Republic of Croatia Formalize Alliance

Dr. Radovan Fuchs, Dr. Darko Milinović, and Dr. Joe Harford at the March 25 signing ceremony From left to right: Dr. Radovan Fuchs, Dr. Darko Milinović, and Dr. Joe Harford at the March 25 signing ceremony

On March 25, NCI and two ministries of the Republic of Croatia signed a memorandum of understanding (MOU). The MOU solidifies ongoing collaborations between NCI and Croatian scientists and provides a vehicle for short- and longer-term exchanges of clinician-scientists and nurses engaged in clinical cancer research.

The memo was signed in Cavtat, Croatia, by Deputy Prime Minister Dr. Darko Milinović, who is also minster of health and social welfare; Minister of Science, Education, and Sports Dr. Radovan Fuchs; and Dr. Joe Harford, director of NCI’s Office of International Affairs. Dr. Steven Pavletic of NCI’s Center for Cancer Research also represented NCI at the signing ceremony.