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Clinical Trials Point to New Options for Advanced Prostate Cancer
Two more treatments for men with advanced prostate cancer could soon be available, according to updated findings from two phase III clinical trials presented in San Francisco last week at the 2012 Genitourinary Cancers Symposium. Read more > >
Additional Surgery after Breast-Conserving Surgery Varies WidelyStudy highlights lack of consensus on what defines successful tumor removal
Comparing Prostate Cancer Treatments Shows Newer Isn't Always BetterOlder, less expensive, less toxic treatments may be better, but more studies are needed
Oral HPV Infections May Explain Why Some Head and Neck Cancers are More Common in MenCancer-linked HPV-16 infections are more common in men than in women
Cancer Screening Rates Lag Behind National Target LevelsBreast, cervical, and colorectal cancer screening fall below Healthy People 2020 goals
HPV Testing with Self-Collected Samples May Be Valid Cervical Cancer Screening MethodMethod could expand access to screening in rural and low-resource areas
Genetic Studies Uncover Clues to Childhood Brain CancersSome cases may involve changes in the chromatin structure
Also in the Journals: CDC Advisory Committee Strengthens Recommendation for HPV Vaccination in Males
Global Health through Collaboration and Leadership
by Dr. Nils Daulaire
To mark World Cancer Day on February 4, the director of the Office of Global Affairs at the U.S. Department of Health and Human Services talks about why the United States should be involved in initiatives to improve global health.
A Conversation with Drs. Christopher Kinsinger and Henry Rodriguez about Sharing Proteomics Data
Experts from NCI's Office of Cancer Clinical Proteomics Research discuss recommendations for setting standards to ensure data quality.
Studies Highlight Complexities of Treating Advanced Head and Neck CancerResults lead to different recommendations for clinical trials in the United States and Europe
Connecting the Dots: Network Analysis Helps Public Health Researchers Get the Big PictureMapping key relationships, whether in cells or society, may reveal factors that influence human health
Featured Clinical Trial: Cetuximab and Radiotherapy for HPV-Associated Oropharynx CancerWill substitution of cisplatin with cetuximab result in comparable 5-year overall survival?
FDA Update
- Drug to Treat Basal Cell Skin Cancer Approved after Priority Review
- Drug Approved for Advanced Kidney Cancer
- Imatinib Granted Expanded Use in Patients with Rare Gastrointestinal Tumors
- NCI Wins Two Awards for Tech Transfer Excellence
- Kevin White to Speak on Genomic Networks in Development and Cancer
- NCI to Hold Symposium on Translational Genomics
- New Issue of CCR Connections Published
- Smartphone App to Help Teens Quit Smoking Now Available
Selected articles from past issues of the NCI Cancer Bulletin are available in Spanish.
The NCI Cancer Bulletin is produced by the National Cancer Institute (NCI), which was established in 1937. Through basic, clinical, and population-based biomedical research and training, NCI conducts and supports research that will lead to a future in which we can identify the environmental and genetic causes of cancer, prevent cancer before it starts, identify cancers that do develop at the earliest stage, eliminate cancers through innovative treatment interventions, and biologically control those cancers that we cannot eliminate so they become manageable, chronic diseases.
For more information about cancer, call 1-800-4-CANCER or visit http://www.cancer.gov.
NCI Cancer Bulletin staff can be reached at email@example.com.
Featured Article
Clinical Trials Point to New Options for Advanced Prostate Cancer
Two more treatments for men with advanced prostate cancer could soon be available, according to updated findings from two phase III clinical trials presented in San Francisco last week at the 2012 Genitourinary Cancers Symposium.
In the trials, the investigational agents MDV3100 and radium-223 (Alpharadin) improved overall survival in men with metastatic castrate-resistant prostate cancer—that is, cancer that no longer responds to treatments that dramatically diminish the testosterone available in the body to fuel tumor growth.
The drugs, which work by different mechanisms of action, also controlled the growth of bone metastases—the most common site of tumor spread in prostate cancer—and caused few serious side effects. Both trials were stopped early because of the survival improvements, and the investigational drugs were offered to patients who had not received them during the trials.
If the Food and Drug Administration (FDA) approves both drugs, which several researchers said is likely, the number of approved treatments for men with advanced castrate-resistant prostate cancer would rise to six—up from only a single approved agent, the chemotherapy drug docetaxel, in 2004.
FDA-Approved Drugs for Treating Advanced Prostate Cancer
|Year Approved
|Drug Class
|Cabazitaxel (Jevtana)
|Abiraterone (Zytiga)
|CYP17 inhibitor (inhibits production of testosterone)
|Sipuleucel-T (Provenge)
The FDA is reviewing MDV3100 and radium-223 under the fast-track designation for treatment of men with metastatic castrate-resistant prostate cancer. The fast track designation is used to expedite the review of drugs for serious conditions for which there is an unmet medical need.
"This is a very exciting time," said Dr. Leonard Gomella of the Thomas Jefferson University Kimmel Cancer Center, who was not involved in either trial. "We have so many new options for patients with advanced castrate-resistant prostate cancer, agents with different mechanisms of action to treat the cancer in different ways. It's very good news for patients."
Different Agents, Similar Results
More than 900 patients with advanced prostate cancer that had spread only to the bones were enrolled in the smaller of the two trials, dubbed ALSYMPCA, which compared treatment with radium-223 plus best supportive care to placebo plus best supportive care.
Radium-223, developed by the Norwegian company Algeta, is the first of a class of drugs called alpha-particle emitters to advance this far into clinical studies. Because it is a "calcium mimic"— like calcium, it targets areas of bone undergoing changes such as those induced by tumors—the drug is designed to target bone metastases, the trial's lead investigator, Dr. A. Oliver Sartor of the Tulane University Cancer Center, said during a press briefing.
We have so many new options for patients with advanced castrate-resistant prostate cancer, agents with different mechanisms of action to treat the cancer in different ways. It's very good news for patients.
—Dr. Leonard Gomella
Once in the bone, radium-223 emits very low levels of alpha radiation, which travels less than 100 microns, or approximately four one-thousandths of an inch. The drug radiates the tumors and surrounding areas "in a very localized fashion," Dr. Sartor said, "like a little bomb going off but [one] that doesn't affect surrounding tissues very much at all."
The results presented last week were from an interim analysis of 805 patients in the trial. The analysis showed a median overall survival of 14 months in patients treated with radium-223 versus 11.2 months in patients treated with placebo. Patients who received radium-223 also lived significantly longer before experiencing bone-related events such as fractures or spinal compressions, a median of 13.6 months compared with 8.4 months for those in the placebo group.
Delaying the onset of bone events is clinically important, said Dr. Philip Saylor of Massachusetts General Hospital, who was not involved in the trial. "Such an overwhelming burden of the disease takes place in the skeleton," Dr. Saylor said. It's also a promising sign, he continued, that radium-223 doesn't appear to cause bone marrow suppression, a problem that has been seen with investigational beta-particle emitters.
The other trial, AFFIRM, tested MDV3100, a drug that targets androgen receptors on cells.
Until fairly recently, the prevailing thought was that prostate tumors that continued to grow despite extremely low levels of testosterone in the body were using a mechanism that does not involve testosterone. But laboratory studies have convincingly shown that tumor cells "have their own mechanisms for making androgens at the local tumor site or figuring out ways to turn on androgen receptors to help them grow," Dr. Gomella explained.
MDV3100—which is being co-developed by San Francisco-based Medivation, Inc. and Tokyo-based Astellas Pharma, Inc.—works by two routes, preventing testosterone from binding to androgen receptors and, within the cell, preventing the androgen receptor from initiating the production of proteins that induce tumor growth.
It's plausible that combinations or sequential use of these agents may add even more value than what we've seen here.
—Dr. A. Oliver Sartor
Nearly 1,200 men, all of whom had castrate-resistant prostate cancer that had progressed after treatment with docetaxel, took part in AFFIRM. The median overall survival was 18.4 months for patients treated with MDV3100 and 13.6 months for those treated with placebo.
Approximately one-third of patients treated with MDV3100 had partial or complete shrinkage of their tumors, compared with 1.3 percent of patients in the control arm, explained the trial's lead investigator, Dr. Howard Scher of Memorial Sloan-Kettering Cancer Center. Treatment with MDV3100 also substantially lengthened the amount of time patients lived without the progression of metastatic tumors (as measured by imaging studies), 8.3 months compared with 2.9 months.
The results, Dr. Scher noted, "will likely position" MDV3100 as the initial treatment in patients with advanced castrate-resistant prostate cancer whose disease progresses after docetaxel treatment.
Next Steps: Treatment Sequencing and Combinations
With several options for treating castrate-resistant prostate cancer, much of the discussion among researchers and clinicians centers on how best to use them—in particular, in what order.
Given the different mechanisms of action and survival improvements seen with MDV3100 and radium-223, using the drugs sequentially could be a particularly promising approach, Dr. Nicholas Vogelzang of the Comprehensive Cancer Centers of Nevada said during the press briefing.
Dr. Sartor agreed. "Whether there are additive or even synergistic benefits will have to be demonstrated in trials," he said, "but it's plausible that combinations or sequential use of these agents may add even more value than what we've seen here."
Combining approved and investigational agents is also high on the research agenda. In asymptomatic patients, combining immunotherapeutic treatments like sipuleucel-T with newer androgen-directed therapies may be a valuable approach, Dr. Gomella said. In patients with progressive disease, treatments that incorporate chemotherapy combined with radium-223 may be particularly effective.
"Of course this is all theory," he said. "But we're very excited that we can even be talking about these theories right now."
Cancer Research Highlights
Additional Surgery after Breast-Conserving Surgery Varies Widely
A new study has found that the number of women who have one or more additional surgeries to remove suspected residual tumor tissue (re-excisions) following breast-conserving surgery (BCS) for breast cancer varies widely across surgeons and hospitals. Although researchers, led by Dr. Laurence E. McCahill from the Richard J. Lacks Cancer Center in Grand Rapids, MI, could not determine whether this variation affected rates of tumor recurrence, "the wide level of unexplained clinical variation itself represents a potential barrier to high-quality and cost-effective care," the authors wrote in a report that appeared February 1 in JAMA.
The researchers pooled data on women with breast cancer diagnosed between 2003 and 2008 who had undergone a first BCS procedure at the University of Vermont or at one of three sites in the HMO Cancer Research Network (Group Health, Kaiser Permanente Colorado, and Marshfield Clinic). Of the 2,206 women eligible for inclusion in the study, 509, or 23 percent, had one or more breast surgeries after the initial BCS. Of these women, 190, or about 8.5 percent of those who underwent initial BCS, had a total mastectomy.
A total of 311 women, or 14 percent, had positive margins (some tumor cells left at the site of surgery, as determined by a pathologist) after their initial surgery, but only about 86 percent of those women underwent re-excision. "This finding is notable given that positive margins…have been correlated with a long-term increased risk of local recurrence," the authors stated.
The percentage of women with positive margins who underwent re-excision differed among institutions, from 73.7 percent to 93.5 percent. The re-excision rates also varied substantially among individual surgeons, from zero percent to 70 percent. Whether these variations were influenced by pathological features of the tumors, clinical factors such as whether women received radiation therapy, or preferences of individual women could not be determined from the study.
Currently, the authors explained, there is no consensus about the appropriate size of a surgical margin around a tumor to be considered "clear." As a result, in this study, nearly half of patients with pathologically clear margins that were less than 1 mm wide and one-fifth of patients with clear margins between 1 and 1.9 mm underwent re-excision.
"I think it's clear that we have to do more clinical research to really understand what's behind this variation: how much of it is clinically appropriate—including where patient preference may be driving some of that variation—and how much of it is really driven by factors that could be mediated by things like better education and better resources in the operating suites," commented Dr. Steven Clauser, chief of the Outcomes Research Branch in NCI's Division of Cancer Control and Population Sciences.
Comparing Prostate Cancer Treatments Shows Newer Isn't Always Better
Two studies comparing the benefits and harms of different prostate cancer treatments show that newer, more expensive approaches may not produce better outcomes. The two comparative effectiveness research studies are among the first to compare newer therapies directly with older ones. The findings were presented at the 2012 Genitourinary Cancers Symposium.
Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, Dr. Ronald Chen of the University of North Carolina at Chapel Hill and his colleagues compared data on more than 12,000 men with localized prostate cancer who had received one of three types of external-beam radiation therapy treatment: three-dimensional conformal radiation therapy, intensity modulated radiation therapy (IMRT), and proton therapy.
Compared with patients who received conformal radiation, patients who received IMRT had a 9 percent lower incidence of gastrointestinal side effects, were 20 percent less likely to have hip fractures, and were 19 percent less likely to receive additional cancer treatments. These differences suggest that IMRT offers better cancer control, Dr. Chen explained at a press conference at the symposium.
Compared with IMRT, proton therapy produced higher rates of gastrointestinal side effects and no improvement in cancer control, as measured by the need for additional cancer treatments.
"I think, based on these data, we can safely say…that there is no clear evidence that proton therapy is better than IMRT. And given the costs and potential increased toxicities [of proton therapy], we must continue to study this modality," said Dr. Nicholas Vogelzang of the Comprehensive Cancer Centers of Nevada, who moderated the press conference.
In another study, Dr. Jay Ciezki of the Cleveland Clinic and his colleagues used SEER-Medicare data to compare the benefits and harms of external-beam radiation therapy, brachytherapy, and surgery for prostate cancer. The researchers found that external-beam radiation therapy was the most toxic, most expensive, and most commonly used of these techniques.
Brachytherapy, although it was the least toxic and the least expensive, was used in only 12 percent of the patients. The limited use of brachytherapy may be due to the fact that it was initially thought to be suitable only for a small subset of men, but "I think people have gotten to the point where they're more comfortable offering [brachytherapy]," said Dr. Ciezki.
See also: "Comparative Effectiveness Research Stirs Excitement as Well as Debate"
Oral HPV Infections May Explain Why Some Head and Neck Cancers are More Common in Men
The prevalence of human papillomavirus (HPV) infections in the oral cavity is significantly higher among men than women in the United States, according to a new study from researchers at Ohio State University and NCI's Division of Cancer Epidemiology and Genetics (DCEG). Oral HPV infections have been associated with oropharyngeal cancer—a subset of head and neck cancers that arise in the back of the tongue, throat, and tonsils—rates of which have risen dramatically over the last several decades.
The study is the first to comprehensively document the prevalence of oral HPV infections in men and women in the United States. Overall, approximately 7 percent of people between the ages of 14 and 69 have an oral HPV infection, reported lead investigator Dr. Maura Gillison last week at the Multidisciplinary Head and Neck Cancer Symposium. (The prevalence of oral infections, however, is much lower than that of infections in the genital tract.) About 1 percent of the population has an oral infection with HPV 16, a type that is linked to cancer. The results were also published online January 26 in JAMA.
Using data from the National Health and Nutrition Examination Survey (NHANES), the researchers studied nearly 5,600 men and women ages 14 to 69, who provided an oral rinse and mouthwash gargle samples. The most common subtype of HPV in the oral cells of study participants was HPV 16, the HPV type that is responsible for more than half of all oropharyngeal cancer cases.
Oral HPV infections were three times more common in men than in women (10.1 percent versus 3.6 percent), with older men having the highest rates, Dr. Gillison said during a press briefing. Oral infections with HPV 16 were seen in 1.6 percent of men and 0.3 percent of women. The prevalence of HPV infections was highest among people who smoke at least a pack a day and those with more than 20 lifetime sexual partners.
HPV-related head and neck cancers are far more common among men than women, Dr. Gillison said. The higher oral HPV infection rates in men, "in particular the over fivefold higher prevalence of HPV 16 among men compared to women," likely explains the discrepancy, she said.
As for why men are more likely to be infected, the available data, she said, "suggest that men are more prone to getting [HPV] infections…or, once infected, are more likely to have the infection persist." It could also be a combination of both factors, she continued.
"These findings are particularly relevant because, in contrast to other head and neck cancers, HPV-associated oropharyngeal cancer rates have been on the rise in recent years," commented senior author Dr. Anil Chaturvedi of DCEG's Infections and Immunoepidemiology Branch. "The higher prevalence of both cigarette smoking and oral HPV infection in men helps complete our understanding of why men have higher rates of oropharyngeal cancer than women."
See also: "Rising Oropharyngeal Cancer Rates Linked to HPV Infection"
Cancer Screening Rates Lag Behind National Target Levels
Screening rates for breast, cervical, and colorectal cancer remained lower in 2010 than national objectives set forth in Healthy People 2020, measures set by the Department of Health and Human Services to improve the health of Americans and gauge the impact of prevention activities. The findings appeared in the January 27 Morbidity and Mortality Weekly Report (MMWR).
2010 U.S. Cancer Screening Rates and Target Screening Rates for 2020
|Screening for
|Percent Screened
|Healthy People 2020 Target
|Breast cancer
|Cervical cancer
|Colorectal cancer
Based on findings from the National Health Interview Survey (NHIS), scientists from NCI's Division of Cancer Control and Population Sciences (DCCPS) and from the Centers for Disease Control and Prevention (CDC) reported that from 2000 to 2010, "the population-based estimates in this report show a slight downward trend in the proportion of women up-to-date with screening for cervical cancer but no change over time in breast cancer screening rates," Colorectal cancer screening rates for men and women increased substantially, the report showed, and by 2010 were generally the same for both sexes.
Rates of all three cancer screening tests were significantly lower among Asians than among whites and blacks, the report noted. Hispanics were less likely than non-Hispanics to be screened for cervical and colorectal cancer.
"Higher screening rates were positively associated with education, availability and use of health care, and length of U.S. residence," the researchers added. For breast cancer, "immigrant women who had been in the United States for 10 or more years were almost as likely as U.S.-born women to report having had a mammogram within the past 2 years (70.3 percent and 73.1 percent, respectively)," the article stated, "whereas only 46.6 percent of immigrants [who had been] in the United States for less than 10 years reported being screened in the past 2 years."
"Healthy People objectives are important for monitoring progress toward reducing the burden of cancer in the United States," said Dr. Carrie Klabunde, an epidemiologist with DCCPS and a co-author of the study. "Our study points to the particular need for finding ways to increase the use of breast, cervical, and colorectal cancer screening tests among Asians and Hispanics, as well as among adults who lack health insurance or a usual source of health care."
HPV Testing with Self-Collected Samples May Be Valid Cervical Cancer Screening Method
Data from five large studies carried out in China demonstrate that self-HPV testing—in which a woman collects a sample of her own cervical-vaginal cells for human papillomavirus (HPV) DNA testing—is as sensitive as the standard liquid-based Pap test for cervical cancer screening. This method has the potential to make cervical cancer screening available to women in rural or low-resource areas who do not have ready access to cytology screening services. The results were published online January 23 in the Journal of the National Cancer Institute.
Pap screening is often unavailable in low-resource areas. Instead, health care providers sometimes use visual inspection with acetic acid (VIA) to look for abnormal cervical cells that can be treated before they progress to cancer. However, VIA is not very accurate, and women still need the time and means to attend appointments with a health provider.
The researchers pooled data from cervical screening studies conducted in China between 1999 and 2007 that included more than 13,000 women between the ages of 17 and 56. The participants underwent an HPV test on a self-collected cervical specimen, VIA, HPV test on a physician-collected cervical specimen, and liquid-based Pap test. Women with positive results on any screening test received a colposcopy and a biopsy of any cervical lesion. By comparing the test and biopsy results, the researchers were able to determine the sensitivity and specificity of each screening method.
Although self-HPV testing proved less sensitive than clinician sampling, self-HPV testing was more sensitive than VIA and as sensitive as the Pap test at identifying cervical precancer or cancer. However, the self-collected samples produced more false-positive results than the Pap test or VIA, meaning that more women who did not have cervical precancer or cancer underwent a colposcopy and biopsy. The researchers showed that conducting follow-up VIA or Pap tests on women whose self-collected sample tested positive could reduce the colposcopy rate from around 16 percent to less than 5 percent but would result in some loss of sensitivity for diagnosing abnormalities.
While acknowledging that self-HPV testing "is not specific enough to be a stand-alone test," the authors point out that it "provides sensitive results without pelvic exams, medical professionals, or health-care facilities and thus has the potential to serve as a primary cervical cancer screening method for women, regardless of their geographic location or access to health care. Limited resources can then be focused on the clinical follow-up of the smaller percentage of women who tested positive."
The authors of an accompanying editorial contend that more research is needed before self-HPV testing can be used outside of a research setting. Both the editorialists and the authors noted that the study participants received physician instruction on sample collection, and it is unclear whether the same results would be obtained by women who did not receive this instruction. Women's willingness to participate in this type of screening and their ability to access follow-up care also need to be investigated.
Genetic Studies Uncover Clues to Childhood Brain Cancers
Two genetic studies of brain tumors in children have identified a new suspect in these deadly cancers. In each study, researchers found recurrent mutations in a protein that helps package DNA in the cell nucleus. Changes to this process may alter the activity of genes and contribute to cancer, the researchers reported.
In one study, published online January 29 in Nature, researchers sequenced the entire exome (all protein-coding DNA) of tumors from 48 children with glioblastoma multiforme (GBM), an aggressive form of brain cancer. The sequencing revealed two recurrent mutations in a gene called H3F3A, which encodes a histone protein (H3.3).
Histones assemble into structures called nucleosomes, around which long strands of DNA wrap, resulting in a tightly packaged complex called chromatin. Because histones interact so closely with DNA, structural modifications to histone proteins can also control gene activity.
Two recent studies (here and here) have found evidence that mutations in genes whose products modify histones may be involved in cancer. The Nature study, however, is the first to describe mutations in a histone gene in tumors. "Histones are, in a way, the guardians of our genetic information," said Dr. Nada Jabado of McGill University, who led the research.
She and her colleagues also found that some GBM tumors had mutations in genes that are involved in chromatin remodeling, a process in which chromatin "opens" so that transcription factors can gain access to DNA, allowing previously silent genes to be transcribed. Defects in the chromatin remodeling pathway may be common in pediatric GBM and could be the basis for exploring much-needed new treatments for the disease, the study authors concluded.
"We now have a starting point for investigating the biological basis of this disease," Dr. Jabado continued. "Until now, we essentially have been working in the dark."
In a separate study, researchers with the Pediatric Cancer Genome Project also found the same mutations in H3F3A or a closely related gene, HIST1H3B, in 78 percent of tumors from 50 children with a cancer known as diffuse intrinsic pontine glioma (DIPG). The findings were reported online in Nature Genetics on January 29.
"It's not often that you find a mutation that affects such a high proportion of [patient samples]," said senior author Dr. Suzanne Baker of St. Jude Children's Research Hospital. "This tells us that anything we learn about this mutation will reveal something important about the biology of this disease."
The finding also adds weight to the idea that epigenetic processes are being undermined in some cancers, Dr. Baker added. "I expect that significant resources will now be devoted to understanding how and why alterations in the histone proteins contribute to cancer."
Also in the Journals: CDC Advisory Committee Strengthens Recommendation for HPV Vaccination in Males
The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices (ACIP) has strengthened and expanded its recommendation for vaccinating boys and young men with the quadrivalent human papillomavirus (HPV) vaccine, primarily to reduce the risk of anal cancer, penile cancer, and certain types of head and neck cancers caused mainly by HPV 16. The updated recommendations were published in Morbidity and Mortality Weekly Report last October and online January 31 in the Annals of Internal Medicine.
ACIP calls for the "routine [HPV] vaccination of males aged 11 to 12 years, with catch-up vaccination recommended for males aged 13 to 21 years." The recommendations specifically call for vaccination with Gardasil, which protects against infection with four HPV types: 6, 11, 16, and 18. Types 6 and 11 cause genital warts, and types 16 and 18 cause cancer.
ACIP also recommends HPV vaccination for "previously unvaccinated males aged 22 to 26 years who are immunocompromised, who test positive for HIV infection, or who have sex with men."
In the previous update, in January 2010, ACIP made a permissive recommendation—a weaker advisory that suggests a vaccine may be given—for males aged 9 to 26 to be vaccinated with Gardasil for the prevention of genital warts.
Guest Commentary by Dr. Nils Daulaire
This article is part of a series of stories related to global health. You can read more articles in the series here. This story is also available in Spanish.
Global Health through Collaboration and Leadership
Every year, an estimated 530,000 women around the world develop cervical cancer. About half of them die from this preventable, treatable disease. More than 85 percent of these women who die needlessly live in low-resource settings, such as the villages of Northern India, where a clinical trial recently showed what can be achieved when researchers come together to focus on improving global health.
The trial demonstrated that women who had a single screening exam for cervical cancer using a DNA test for the human papillomavirus (HPV)—the virus that causes the vast majority of cervical cancers—had half the rate of advanced disease and cervical cancer deaths over 8 years compared with women who received usual care.
Sadly, for many women in developing countries, usual care typically means no screening at all. In fact, only eight of the more than 130,000 women in the trial had ever been previously screened for cervical cancer.
Although cervical cancer typically develops slowly over the course of many years, most women in these countries do not have access to life-saving screening and early treatment. In many communities, few women know that cervical cancer is preventable. The consequences are predictable: Cervical cancer is among the most common causes of death in women in developing countries. (See the related story on cervical cancer screening in this issue.)
This is in sharp contrast, of course, with the United States and other industrialized nations, where regular screening for cervical cancer has drastically reduced rates of this disease over the past four to five decades—a significant public health achievement. And yet, in this trial, with just a single screening test—a highly feasible approach in northern India and many other parts of the world—the amount of good achieved was remarkable.
Research successes such as this and the need for improved global education are at the heart of events like World Cancer Day, which was marked on February 4 by events around the globe. Launched by the Union for International Cancer Control, World Cancer Day is focused on raising global awareness about cancer and urging action at all levels, from governments to individuals, to reduce the cancer burden. Clearly, action is needed: nearly two-thirds of the 7.6 million cancer deaths in 2008 were in low- and middle-income countries. And, due in part to factors such as escalating rates of smoking and obesity, the number of preventable cancer deaths in these countries is expected to rise precipitously in the coming decades.
In the same vein, the recognition of the global threat posed by problems such as cancer, infectious diseases, and unsafe drinking water, among many others, led the U.S. Department of Health and Human Services (HHS) to develop its first-ever department-wide Global Health Strategy. Released at the start of 2012, the HHS Global Health Strategy is not a start-from-scratch initiative. Rather, it is designed to strategically integrate, coordinate, and prioritize the excellent work already being conducted globally by numerous HHS agencies in areas such as food safety, drug and device regulation, and disease prevention.
As HHS Secretary Kathleen Sebelius explained at the launch of the HHS Global Health Strategy at the Kaiser Family Foundation, the strategy is intended "to provide a new focus going forward so that we can use HHS' unique expertise, resources, and relationships to make the biggest impact possible." Helping low-resource countries reduce cancer deaths through improved screening and treatment—whether it's helping to establish infrastructure, training health care workers, or aiding in the procurement of affordable screening tests—is an ideal example of how the United States can use its scientific expertise to improve and save lives around the world.
Our department's primary objective, of course, is to promote the health and well-being of Americans. But the world is now a far more interconnected place than it was even a decade ago. Single events or larger population trends can have a significant impact on life within our borders. One need only look at the rapid worldwide spread of the H1N1 flu virus in 2009 as a convincing example that we ignore global health at our own peril.
The HHS Global Health Strategy, which is framed by 3 overarching goals and 10 strategic objectives, has several common themes, including collaboration, enhanced safety, prevention, leadership, and expertise.
The work done by NIH and NCI certainly embodies these themes; these world-class institutions are already established leaders in global health. Upon being appointed, both NIH Director Dr. Francis Collins and NCI Director Dr. Harold Varmus recognized that more needs to be done, naming improved global health among their top priorities.
Dr. Varmus established the NCI Center for Global Health. This center, by better coordinating and prioritizing NCI's global health activities, is well aligned with the HHS Global Health Strategy and will be an invaluable asset in this effort.
Meanwhile, existing NCI programs are already providing needed resources for new global health initiatives. At the recent United Nations High-Level Meeting on the Prevention and Control of Noncommunicable Diseases, a multinational partnership was announced to help combat a mounting scourge in many developing countries: skyrocketing rates of tobacco use.
Under the partnership—which includes HHS, the UN Foundation's mHealth Alliance, the Campaign for Tobacco-Free Kids, Johnson and Johnson, and several other U.S. and international groups—demonstration projects on smoking cessation will be launched in a handful of developing countries. The projects will rely heavily on text messages from NCI's QuitNowTXT library, developed as part of the institute's SmokefreeTXT initiative. The demonstration projects will also help to identify, document, and disseminate best practices for implementing tobacco cessation interventions.
As President Barack Obama made clear in the U.S. Global Health Initiative (GHI), healthy societies are far more likely to be stable societies—politically, economically, and diplomatically. GHI aims to reduce death and disease through a comprehensive, government-wide approach emphasizing coordination of activities across agencies and sectors. The HHS Global Health Strategy is a critical adjunct to the president's initiative.
As World Cancer Day reminds us, given the United States' leadership role in cancer research and care delivery, the entire cancer community has a potential role to play in this vital effort. This role could include expanding collaborations on international clinical trials, establishing training programs specifically for researchers and patient advocates from developing countries, or sharing educational resources and medical equipment.
There are numerous ways in which the U.S. cancer community can play its part, and I strongly encourage you to seek out such opportunities. The reward, I believe, will be returned many times over in better health for all of the world's citizens.
Dr. Nils Daulaire
Director, Office of Global Affairs
U.S. Department of Health and Human Services
A Conversation With
A Conversation with Drs. Christopher Kinsinger and Henry Rodriguez about Sharing Proteomics Data
Last September, NCI's Office of Cancer Clinical Proteomics Research convened a workshop of researchers and stakeholders in the field of proteomics to discuss ways to better share data about the structure and functions of proteins—a challenge facing the entire proteomics community. The meeting, held in Sydney, Australia, addressed establishing standards to ensure the quality of the data, particularly those generated by a technique known as mass spectrometry. A meeting report with recommendations for the field was recently published simultaneously in four journals simultaneously.
Why is open access to proteomics data important?
Dr. Kinsinger: We believe that advances in science can be accelerated when the research community has open access to high-quality data. In coordination with the international proteomics community, NCI is leading efforts to implement policies that govern the adoption and use of quality metrics for open-access proteomic data.
We believe this will enhance the management, integration, and analysis of research data. For example, researchers can use open data to conduct new analyses, which may lead to new insights.
What were the goals of the workshop, and who attended?
Dr. Kinsinger: The goals were to define data quality standards for open-access proteomics data and to build on the Amsterdam Principles. At the Amsterdam meeting, the community coalesced around the need for open access to raw proteomic data from published articles. The intent was to emulate the genomics community's development of the Bermuda Principles of data quality and sharing. The meeting in Australia focused on how we can determine what "quality data" are.
The international workshop included extramural [non-NIH] researchers who produce and use proteomics data, managers of database repositories, editors of scientific journals, and funding agency representatives.
In concrete terms, what did the workshop achieve?
Dr. Rodriguez: The workshop produced specific recommendations for a number of areas, including data annotation; quality metrics and data standards; reference materials; education about data policy; infrastructure for depositing data; and incentives for data sharing such as acknowledging the use of data in publications.
There was also broad agreement about the need for a sustainably funded central repository—or a set of linked repositories—that would work closely with journals to ensure long-term access to proteomics data.
What are the next steps?
Dr. Rodriguez: Several journals have expressed an interest in adopting some of the recommendations and applying them to manuscripts they publish. However, the proteomics field currently does not have stable funding and infrastructure to host proteomics data.
This means that before the journals require authors to deposit data and meet certain quality metrics, there needs to be a reliable place that could host the high-quality raw data.
Can you define "raw data"?
Dr. Kinsinger: Raw data have not been modified beyond the initial processing by the instruments used to create them.
Have you learned from efforts to develop data quality standards in other fields, such as genomics?
Dr. Rodriguez: To move science forward, researchers need and want access to raw data. We realize, however, that often it will take senior investigators and policy-makers to implement policies on depositing data.
Why did you publish the meeting report simultaneously in four journals?
Dr. Kinsinger: This was unprecedented, as far as we know. Based on the overwhelmingly positive feedback they received from meeting attendees and researchers who could not attend, the editorial board of each journal felt it was important to show support for the recommendations. The Journal of Proteome Research, Molecular and Cellular Proteomics, Proteomics, and Proteomics Clinical Applications published the report as a service to the research community.
Were there any disagreements at the meeting?
Dr. Kinsinger: There was some controversy about how data quality will be measured and who would enforce these standards. Many investigators felt that the enforcement of quality standards might stifle innovation in a field that is still rapidly developing technologies.
On the other hand, without standards, no one would know which data to trust.
—Interviewed by Edward R. Winstead
Special Report
Studies Highlight Complexities of Treating Advanced Head and Neck Cancer
In a large randomized European clinical trial, accelerated radiation therapy for locally advanced, inoperable head and neck cancer—given either with or without chemotherapy—did not prolong the time to disease progression compared with standard radiation therapy plus concurrent chemotherapy (chemoradiotherapy), which has been the standard of care in Europe and the United States. Results from the study were published online January 18 in Lancet Oncology.
Another trial published in 2010, by the U.S. Radiation Therapy Oncology Group (RTOG), showed similar results, but the two research teams have drawn different conclusions, which will affect ongoing clinical trials and, potentially, future research collaborations.
The researchers in the latest study, from the European Groupe d'Oncologie Radiothérapie Tête et Cou (GORTEC), compared two experimental regimens with standard chemoradiotherapy in the trial, called GORTEC 99-02. All participating patients had stage III or stage IV head and neck squamous-cell carcinoma that had not metastasized but that could not be removed surgically.
The 244 patients in the conventional chemoradiotherapy arm received three cycles of chemotherapy with the drugs carboplatin and fluorouracil plus 70 Gy of radiation given over the standard 7 weeks.
In one experimental arm, 245 patients received "accelerated chemoradiotherapy," which consisted of two cycles of the same chemotherapy drugs plus radiation therapy accelerated by 1 week. In the second experimental arm, 242 patients received only "very accelerated" radiation therapy, which consisted of a total dose of 64.8 Gy given over 3.5 weeks. (See the tables below.)
Treatment Groups in the GORTEC 99-02 Trial
|Radiation Therapy
|Conventional Chemoradiotherapy
|70 Gy given over 7 weeks:
|3 cycles of:
|Accelerated Chemoradiotherapy
|70 Gy given over 6 weeks:
|2 cycles of:
|Very Accelerated Radiotherapy
|64.8 Gy given over 3.5 weeks:
Treatment Groups in the RTOG-0129 Trial
|Radiation Therapy
|Conventional Chemoradiotherapy
|70 Gy given over 7 weeks:
|3 cycles of:
|Accelerated Chemoradiotherapy
|72 Gy given over 6 weeks:
|2 cycles of:
On the basis of promising earlier studies of accelerated radiation, the authors hypothesized that the more intense dose of radiation would improve progression-free survival and disease control.
Instead, the trial "showed that there was no such benefit and that acceleration of radiotherapy by 1 week, concomitant to chemotherapy, did not add any benefit when compared with conventional concomitant chemoradiotherapy," wrote the authors. Three years after treatment, 37.6 percent of patients in the conventional chemoradiotherapy arm were alive without progression of their disease, compared with 34.1 percent of those in the accelerated chemoradiotherapy arm.
The very accelerated radiation regimen provided inferior disease control compared with conventional chemoradiotherapy, with 32.2 percent of patients in that group alive and free of disease progression 3 years after treatment. These results were another surprise: "We expected 'very accelerated' radiotherapy to be at least as good as conventional chemoradiotherapy," stated the authors.
Same Results, Divergent Conclusions
The GORTEC trial results are somewhat difficult to interpret because the trial "didn't change just one variable, it changed two—in addition to the radiation regimen, it also changed the chemotherapy," explained Dr. Bhadrasain Vikram, chief of the Clinical Radiation Oncology Branch of the Radiation Research Program in NCI's Division of Cancer Treatment and Diagnosis.
Because patients in the accelerated chemoradiotherapy group received two, rather than three, cycles of chemotherapy (although those two cycles were longer in duration), they received 17 percent less chemotherapy overall than patients in the conventional chemoradiotherapy group.
The RTOG trial that showed similar results (RTOG-0129) also reduced the amount of chemotherapy given, and not just because of fears of toxicity, explained Dr. Maura Gillison, RTOG investigator and professor of medicine at the James Comprehensive Cancer Center at Ohio State University.
—Dr. Maura Gillison
"All of the studies have shown that it's critical to give the chemotherapy with the radiation," she stressed. Chemotherapy given alone does not have as potent an antitumor effect in head and neck cancer, and in the accelerated chemoradiotherapy arms of the two trials, shortening the duration of radiation therapy did not leave enough time for a third cycle of chemotherapy.
Because only about 60 percent of patients with advanced head and neck cancer are healthy enough to complete the third cycle of chemotherapy with conventional chemoradiotherapy, and because the patients in RTOG-0129 who received conventional and accelerated chemoradiotherapy survived for a similar length of time, "we thought that to some extent our results are an advance," Dr. Gillison said. "You can shorten the treatment to 6 weeks instead of 7, and shortening the treatment means you don't have to give that third cycle of chemotherapy, with all its associated toxicities."
While the GORTEC investigators did not see a benefit from accelerated chemoradiotherapy, the RTOG investigators have chosen to use an accelerated chemoradiotherapy regimen as the standard of care in their trials of advanced head and neck cancer.
This decision for trials in the United States was also influenced by changes in modern radiation therapy technology, explained Dr. K. Kian Ang, professor of radiation oncology at the University of Texas M. D. Anderson Cancer Center and former chair of RTOG's Head and Neck Committee. The more widespread availability of intensity modulated radiation therapy (IMRT) has allowed radiation oncologists to reduce the number of visits required for irradiation even further than in the RTOG-0129 trial, which makes it more practical for patients to complete therapy, added Dr. Ang.
HPV Status Makes a Difference
The recent understanding of the importance of human papillomavirus (HPV) as a cause of oropharyngeal cancer also limits the application of the GORTEC results to current practice, added Dr. Vikram. That trial began "before the huge importance of HPV status [in head and neck cancer] was recognized. One would expect about 40 to 50 percent of the tumors in this trial to have been HPV-positive, but the paper unfortunately has no information on that, so we have no idea from this trial if one of the regimens tested might work better for subsets of patients with HPV-positive or HPV-negative tumors," he explained.
Dividing patients into those whose tumors are HPV-positive versus HPV-negative will be increasingly important in future trials for head and neck cancer, as the rate of oral HPV infection continues to rise. In the RTOG-0129 trial, people whose oropharyngeal tumors contain the HPV virus were found to respond much better to treatment than patients with HPV-negative tumors.
"After so many years, we've really started to understand that, although [HPV-positive and HPV-negative tumors] are located in the same small anatomical region, we are dealing with different types of cancers," said Dr. Ang. "Because HPV-positive patients do relatively well on current treatments, one of our main goals now is to reduce toxicity. And for HPV-negative patients, because they do so badly with what we have now, we want to know how we can intensify treatment in order to improve outcomes.
"With these completely different objectives, we don't think we can put [these two groups] in the same protocol—we need to do separate trials," he continued. RTOG recently launched its first trial for HPV-positive patients only (RTOG-1016), to see if using the targeted drug cetuximab instead of cisplatin can reduce the side effects of treatment while controlling tumors.
A big challenge, added Dr. Ang, is that "head and neck cancer is relatively rare, and now we're dividing it into smaller and smaller subsets. International trials will be a necessity to enroll enough patients."
And along with the normal challenges of cross-border funding, quality control, and tumor sample transportation, what should actually be tested will also have to be agreed upon. "Investigators will need to agree on what are the best scientific questions to ask," concluded Dr. Ang.
Connecting the Dots: Network Analysis Helps Public Health Researchers Get the Big Picture
At first glance, the web of interacting molecules that make up a living cell and the peer relationships that influence smoking behavior in a group of middle school students would seem to have little in common. But both are examples of networks: a set of connected actors and the relationships among them.
In recent decades, a small cadre of researchers has turned to network analysis to help find answers to complex, multifaceted problems that underlie cancer and other diseases, from the molecular to the societal level.
Network analysis is the measurement, mapping, analysis, and interpretation of network structures, of the ties between actors, and of the flows that occur within and across networks. This approach, which has its roots in mathematics, is being applied to problems in a broad range of disciplines.
Molecular biologists are using network analysis to get a handle on the complex web of interactions between molecules in a cell and on how defects or changes in various components of these molecular networks can result in diseases such as cancer.
Meanwhile, public health researchers are using network analysis—specifically, social network analysis—to understand complex problems such as tobacco use, obesity, and the HIV/AIDS epidemic. Social network analysis can be used to study how infections, behaviors, attitudes, and information are transmitted among people or groups of people, as well as the adoption of new medical or public health practices.
Networking for Public Health
Public health researchers "now realize that the complexity we're dealing with can't be addressed exclusively with the traditional approaches that we've been using," noted Dr. Elizabeth Ginexi, a program director in NCI's Tobacco Control Research Branch (TCRB).
Social network analysis and other systems science approaches, such as system dynamics modeling and agent-based modeling, "specialize in getting at the relationships between components of a system and the system itself, and particularly how they change over time," added Dr. Patricia Mabry, a senior advisor in NIH's Office of Behavioral and Social Sciences Research (OBSSR).
New tools and techniques for mapping out networks have led network theorists to conclude that "most real networks in technological, social, and biological systems have common designs that are governed by simple and quantifiable organizing principles," according to a 2007 editorial by Dr. Albert-László Barabási, director of Northeastern University's Center for Complex Network Research in Boston. And, Dr. Barabási noted, "networks pervade all aspects of human health."
Signaling Pathways and Tobacco Control
Dr. Scott Leischow, associate director of the Biobehavioral and Social Sciences Research Program at the University of Arizona Cancer Center, developed his interest in social network analysis when he was chief of NCI's TCRB. While at NCI, Dr. Leischow launched the Initiative on the Study and Implementation of Systems (ISIS), which explored the application of social network analysis and other systems science approaches to tobacco control and public health.
At the University of Arizona, Dr. Leischow brings interdisciplinary teams together to do just that. "My goal in studying social networks," he said, "is to figure out where in the network one can intervene to achieve the best health outcome."
In a social network, the actors are usually people or groups of people, such as households, organizations, governments, or even societies, each of which can interact with and influence each other in various ways, directly and indirectly.
One project that Dr. Leischow leads has been using social network analysis to understand how the network of toll-free telephone-based smoking cessation services that make up the North American Quitline Consortium interact and share new knowledge. By sharing his findings on these "signaling pathways" with consortium members, Dr. Leischow hopes to help them better implement evidence-based practices so that they can improve their ability to help tobacco users quit.
Dr. Leischow also recently received a grant as part of the NCI State and Community Tobacco Control Research Initiative to work with Team Navajo, a network of Navajo health advocates and organizations whose aim is to eliminate secondhand smoke from use of commercial tobacco (as opposed to ceremonial use) in all workplaces and indoor public spaces. (The Navajo Nation is sovereign and thus exempt from state laws.) "The problem is most exemplified in places like the casinos, where they allow cigarette smoking and there is a lot of exposure to secondhand smoke, both for people who go there to gamble and among the employees," Dr. Leischow noted.
He and his colleagues plan to analyze the Team Navajo network and its interactions with other organizations and people in the Navajo Nation. By doing so, the researchers hope to help Team Navajo "identify the lynchpin people or organizations"—the thought leaders and key decision makers—with whom they should work to achieve their goal.
Whom You Know Matters
Since the 1990s, Dr. Thomas Valente, a professor in the Department of Preventive Medicine at the University of Southern California (USC), has used social network analysis to understand a range of health-related behaviors, including how peer relationships affect smoking among middle school students. He found that "one of the strongest influences on adolescents beginning and continuing to smoke is having friends who smoke."
Furthermore, Dr. Valente said, "popular students tend to be early initiators of smoking behavior. So if we want to create effective interventions to stem the spread of smoking, we need to recruit those popular students and have them actively involved."
"My goal in studying social networks is to figure out where in the network one can intervene to achieve the best health outcome."
—Dr. Scott Leischow
To see how this would work in practice, Dr. Valente and his colleagues at USC designed smoking prevention programs that use social network data to identify opinion leaders—in this case, popular students in sixth-grade classrooms—and to assign students to groups, "so that the intervention messages are received from peers rather than from randomly selected others," Dr. Valente said. Through a randomized controlled study, the researchers found that their network-based approach was more effective than two other approaches at changing attitudes toward smoking and reducing students' intention to smoke.
In an extension of this work, Dr. Valente and his colleagues "are currently estimating peer influences from networks other than friends, and designing better intervention options," he wrote in an e-mail message.
Dr. Valente also recently led a study that used social network analysis to investigate the effectiveness of a community-based NCI initiative that was designed to reduce cancer disparities among Pacific Islanders in Southern California.
It's Not All about Networks
Dr. Mabry of OBSSR and others at NIH are spearheading efforts to encourage basic research that leads to new applications of social network methods and theory for improving human health. Through its Division of Cancer Control and Population Sciences, NCI and 10 other NIH institutes, as well as OBSSR, are also participating in an NIH funding opportunity announcement that promotes the use of systems science approaches, including network analysis, in behavioral and social science research relevant to health.
"It's a slow train, there's still time for people to get on," Dr. Ginexi said. However, she noted, the goal "is not to replace the existing mathematical and statistical models, but to complement them where it makes sense."
As Dr. Valente, a self-described "avid social network analyst," said in an e-mail message: "Social network analysis will not solve all your problems or provide all the answers, but [it] should be used as a tool with other sources of information. Networks, like many things, can be unpredictable; we still have a lot to learn about network theory."
Two Videos on Network Analysis and Systems Science
Network Analysis: Using Connections and Structures to Understand and Change Health Behaviors
Dr. Katherine Faust of the University of California, Irvine, and Dr. Thomas Valente of the University of Southern California present the second symposium of a four-part series on Systems Science and Health, sponsored by the NIH Office of Behavioral and Social Sciences Research and CDC Syndemics Prevention Network.
Cambridge Nights: Conversations about a Life in Science
Includes video interviews with Dr. Albert-László Barabási, of Northeastern University, on the science of networks; and Dr. Marc Vidal, director of the Dana-Farber Cancer Institute's Center for Cancer Systems Biology, on systems biology and how we can understand the molecular biology of organisms in an integrative way.
Featured Clinical Trial
Cetuximab and Radiotherapy for HPV-Associated Oropharynx Cancer
Name of the Trial
Phase III Randomized Study of Radiotherapy with Cisplatin or Cetuximab in Patients with Human Papilloma Virus-Associated Oropharyngeal Cancer (RTOG-1016). See the protocol summary.
Principal Investigators
Dr. Andy Trotti, Radiation Therapy Oncology Group
Dr. Maura Gillison, Ohio State University Comprehensive Cancer Center
Why This Trial Is Important
Oropharyngeal squamous cell carcinoma (OSCC) is a type of head and neck cancer that forms in the middle part of the throat, which includes the base of the tongue, the tonsils, and the soft palate. Although OSCC was once thought to be a single disease, recent research has revealed that it has two distinct types: cancers that test positive for human papillomavirus (HPV) and those that are HPV negative.
Oropharyngeal tumors negative for HPV have been linked to tobacco and alcohol abuse, whereas HPV-positive malignancies may be related to sexual behavior. Patients with HPV-associated OSCC are likely to be younger at the time of diagnosis and have a better prognosis than those with HPV-negative malignancies. In contrast with the rates of other oral cancers, which have fallen as smoking rates have declined, the incidence of HPV-positive OSCC is on the rise.
Current treatment strategies for oropharyngeal cancer are based on tumor stage, rather than HPV status, and consist of surgery or radiation with or without cisplatin-based chemotherapy. Cancer response rates following cisplatin-based chemotherapy and radiotherapy are generally good, but studies have shown that this combination treatment approach dramatically increases toxic side effects. Since more than 80 percent of patients with HPV-positive tumors survive at least 5 years after diagnosis, these patients may do just as well on a less-toxic regimen.
One study investigating the combination of cetuximab, a monoclonal antibody directed against a protein called EGFR, and radiotherapy in head and neck cancer demonstrated improved patient survival compared with radiation alone. The use of this combination increased skin irritation, but otherwise it had the same side effects as radiotherapy alone. An analysis of patients in this trial revealed that those with OSCC who were male and younger, a group that mirrors the HPV-positive population, benefited most from the combination therapy. These results suggested that radiation plus cetuximab, instead of cisplatin-based chemotherapy, may reduce treatment toxicity without compromising cancer control for patients with HPV-positive OSCC.
In this clinical trial, patients with HPV-positive OSCC will be randomly assigned to receive cisplatin chemotherapy plus intensity-modulated radiation therapy (IMRT) or cetuximab plus IMRT. Prior to treatment, patients will complete a computer-administered survey on head and neck cancer risk factors, including tobacco exposure, alcohol use, and oral hygiene. During and after treatment, patients will also report the toxic side effects they experience. Clinicians will monitor the patients for tumor response, toxicity, quality of life, progression-free survival, and overall survival.
"This is the first randomized phase III trial specific to the HPV-positive patient population," said Dr. Gillison. "There are a lot of quality of life outcomes incorporated [into the trial] about both acute toxicity and long-term toxicity, and the patients are reporting their toxicity experience directly on things like nausea, vomiting, ability to swallow, pain, and energy level using touch-screen surveys.
"It also includes things that we have never looked at before, which will allow us to do a cost-effectiveness analysis. The first potential outcome is that one of the treatments is better than the other. Then we get an answer in terms of disease control. If the two treatments are equivalent, then we see which one gives the patient the best quality of life. There is also the possibility that they are equal and one of them has a cost-benefit to society over the other," Dr. Gillison added.
For More Information
See the lists of entry criteria and trial contact information or call the NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The toll-free call is confidential.
FDA Update
Drug to Treat Basal Cell Skin Cancer Approved after Priority Review
Last week, the Food and Drug Administration (FDA) approved vismodegib (Erivedge) to treat adults with basal cell carcinoma, the most common type of skin cancer. The drug is intended for use in patients with locally advanced basal cell cancer who are not candidates for surgery or radiation and in patients whose cancer has metastasized.
Vismodegib is the first FDA-approved drug for metastatic basal cell carcinoma and was reviewed under the FDA's priority review program, which provides for an expedited 6-month review of drugs that may offer major advances in treatment.
The drug is a pill taken once a day that inhibits the Hedgehog pathway, a molecular pathway that is active in most basal cell cancers and only a few normal tissues, such as hair follicles.
The safety and effectiveness of vismodegib was evaluated in a single-arm, multicenter clinical study of 104 patients with locally advanced or metastatic basal cell carcinoma. The study's primary endpoint was objective response rate, which could be evaluated in 96 patients. Thirty percent of the patients with metastatic disease experienced a partial response, and 43 percent of patients with locally advanced disease experienced a complete or partial response.
The most common side effects were muscle spasms, hair loss, weight loss, nausea, diarrhea, fatigue, distorted sense of taste, decreased appetite, constipation, vomiting, and loss of taste function in the tongue.
Vismodegib was approved with a boxed warning alerting patients and health care professionals of the risk for fetal death or severe birth defects. Pregnancy status must be verified prior to the start of treatment. Patients should be warned about these risks and the need for both male and female patients to use birth control.
Drug Approved for Advanced Kidney Cancer
The Food and Drug Administration (FDA) recently approved axitinib (Inlyta) to treat patients with advanced kidney cancer (renal cell carcinoma) whose disease has not responded to one course of treatment with another drug.
Renal cell carcinoma is a type of kidney cancer that starts in the lining of tubules in the kidney. Axitinib is a pill taken twice a day that works by blocking certain proteins called kinases that play a role in tumor growth and cancer progression.
"This is the seventh drug that has been approved for the treatment of metastatic or advanced kidney cell cancer since 2005," said Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, in a press release. "[These approvals have] significantly altered the treatment paradigm of metastatic kidney cancer, and offer patients multiple treatment options."
The safety and effectiveness of axitinib were evaluated in a randomized, open-label, multicenter clinical study of 723 patients whose disease had progressed during or after treatment with one prior systemic therapy. Results showed a median progression-free survival of 6.7 months versus 4.7 months with a standard treatment (sorafenib).
The most common side effects observed in the clinical study were diarrhea, high blood pressure, fatigue, decreased appetite, nausea, loss of voice, hand-foot syndrome, weight loss, vomiting, weakness, and constipation. Some patients who took axitinib experienced bleeding, which in some cases was fatal. Patients with untreated high blood pressure, untreated brain metastases, or recent gastrointestinal bleeding should not take axitinib.
Imatinib Granted Expanded Use in Patients with Rare Gastrointestinal TumorsThe Food and Drug Administration (FDA) granted imatinib (Gleevec) regular approval for use in adult patients following surgical removal of CD117-positive gastrointestinal stromal tumors (GIST). CD117, or Kit, is a molecular marker found on most GISTs. The approval highlights an increase in overall survival when the drug is taken for 36 months rather than the standard 12 months.
In a large randomized clinical study, GIST patients who took imatinib for 36 months had significantly longer overall survival, and lived longer without the disease recurring, than those who took imatinib for 12 months. At 60 months, 92 percent of patients who took imatinib for 36 months were alive, compared with 82 percent of patients who took it for 12 months.
Imatinib was originally granted accelerated approval for the treatment of metastatic GIST in 2002. In 2008, imatinib received a subsequent accelerated approval for adjuvant use to treat GIST patients who had had their tumors removed but who were at increased risk for a recurrence. Accelerated approval provides earlier patient access to promising new drugs while confirmatory clinical trials are conducted. Regular approval for the metastatic GIST indication was also granted in 2008.
"The development of [imatinib] over the past decade highlights the need to further study drugs after approval to truly characterize their benefits," said Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA Center for Drug Evaluation and Research. "Although originally approved in the metastatic disease setting, this subsequent trial has demonstrated that longer use of [imatinib] can prolong patient's lives in earlier disease settings."
The most common side effects observed in patients receiving imatinib include swelling (edema), nausea, vomiting, muscle cramps, bone or muscle pain, diarrhea, rash, fatigue, and abdominal pain.
NCI Wins Two Awards for Tech Transfer Excellence
Two NCI projects have won the Award for Excellence in Technology Transfer from the Federal Laboratory Consortium for Technology Transfer (FLC). The award is given annually to recognize employees of FLC labs who have accomplished outstanding work while transferring federally developed technology to the private sector.
The first project is a software package used to analyze DNA microarray data. The program brings state-of-the-art statistical and machine learning methodology to investigators. It has been licensed by more than 13,000 laboratories in 65 countries and cited in more than 1,700 publications.Designed as a Microsoft Excel add-in, the program has a familiar interface but is powerful enough to analyze thousands of expression profiles for 50,000 probes. The software was designed by Dr. Richard Simon, chief of the Biometric Research Branch of the Division of Cancer Treatment and Diagnosis (DCTD) and transferred to the scientific community by NCI's Technology Transfer Center using an online distribution system.
The second award was for NCI's role, spearheaded by DCTD's Natural Products Branch, in the development of eribulin, an anticancer agent derived from a marine sponge. The drug was developed in partnership with the pharmaceutical company Eisai and was given FDA priority approval in November 2010 for the treatment of patients with metastatic breast cancer.
Kevin White to Speak on Genomic Networks in Development and Cancer
NCI's Center for Cancer Genomics will host a special lecture by Dr. Kevin White, director of the University of Chicago's Institute for Genomics and Systems Biology, on February 14 at 1:00 p.m. His presentation, titled "Genomic Networks in Development and Cancer: Resolving Biomarkers and Therapeutic Targets from a Cloud of Data," will be held in Lipsett Auditorium on the NIH campus in Bethesda, MD.
Dr. White is a pioneer in combining experimental and computational techniques to understand the factors that control biological systems during development and evolution. He will talk about how his lab uses systems-level approaches to construct abstract molecular networks to make predictions about genetic and biochemical functions in cells, organisms, and disease states.
Dr. White's team is mining data from The Cancer Genome Atlas and the Chicago Cancer Genome Project and using the Bionimbus Cloud to identify new tumor suppressor genes and panels of genetic markers.
More information about the lecture is available online. To watch a live videocast, visit http://videocast.nih.gov/summary.asp?live=10995.
NCI to Hold Symposium on Translational Genomics
Registration is open for the Second Symposium on Translational Genomics sponsored by the NCI Center of Excellence in Integrative Cancer Biology and Genomics. The event will take place March 15–16 in Natcher Auditorium, on the NIH campus in Bethesda, MD.
The field of translational genomics is progressing rapidly, yet systematically applying current knowledge to improve patient care remains a formidable challenge. At the symposium, participants will exchange information on noncoding RNAs, next-generation sequencing, and epigenomics and genetic variation. The goal is to translate these advances into clinical practice and implement them to improve the health of patients with cancer.
To view a list of speakers and to register, visit the symposium's webpage. Registration is free but seating is limited. For additional information please contact Laura Hooper at email@example.com.
New Issue of CCR Connections Published
The latest issue of NCI's Center for Cancer Research (CCR) news magazine, CCR Connections, is now available online. This issue highlights the broad reach of CCR's translational research and showcases its collaborations with intramural and extramural partners, domestic and global, to quickly turn CCR discoveries into clinical advances.
The issue includes stories on:
- Dr. Thomas Waldmann's co-discovery of interleukin-15 and its use in clinical trials through CCR's Center of Excellence in Immunology
- The role that nurses play in bringing experimental approaches and cancer treatments into patient trials and clinical practice
- Dr. Chand Khanna's idea for a consortium of veterinary schools that treat cancers in pets to help accelerate new treatments for humans
- Dr. Michael Dean's vacation to Guatemala that developed into an international collaboration to study the molecular mechanisms involved in pediatric cancers, especially genetic risk factors for acute lymphoblastic leukemia
- Drs. Peter Choyke and Peter Pinto's adaptation of magnetic imaging to guide robotic surgery for prostate cancer
For a print or online subscription to CCR Connections, please send a request to email@example.com.
Smartphone App to Help Teens Quit Smoking Now Available
Teen smokers who want to quit can now download QuitSTART from the Apple App Store for free. QuitSTART is an interactive mobile quit guide for teens that delivers cessation and mood management tips and tracks cravings and progress towards quitting.
The new app is part of Smokefree Teen, an NCI initiative launched in December 2011 to help teens quit smoking.
SmokefreeTXT, a free text-message service that is part of Smokefree Teen, also provides encouragement, advice, and tips to teens trying to quit smoking.


text:
35 U.S. Code § 390 - Publication of international design application
Source(Added Pub. L. 112–211, title I, § 101(a),Dec. 18, 2012, 126 Stat. 1531.)
Effective Date
Section effective on the later of the date that is 1 year after Dec. 18, 2012, or the date that the Geneva Act of the Hague Agreement Concerning the International Registration of Industrial Designs enters into force with respect to the United States, and applicable only to certain applications filed on and after that effective date and patents issuing thereon, see section 103 ofPub. L. 112–211, set out as an Effective Date of 2012 Amendment note under section 100 of this title.
The table below lists the classification updates, since Jan. 3, 2012, for this section. Updates to a broader range of sections may be found at the update page for containing chapter, title, etc.
The most recent Classification Table update that we have noticed was Tuesday, August 13, 2013
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|Description of Change
|Session Year
|Public Law
|Statutes at Large
|§ 390
|112-211 [Sec.] 101(a) "390"
|126 Stat. 1531
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subset: commoncrawl


text:
John Brown
Library of Congress
By Encyclopedia Virginia
John Brown (1800-1859) was a fervent abolitionist who was accused of massacring pro-slavery settlers in Kansas in 1856 and who, in 1859, led an unsuccessful raid on Harpers Ferry, Virginia (in what is now West Virginia), in an attempt to start a slave insurrection.
On October 16, 1859, Brown and his men occupied the federal arsenal in the northern Shenandoah Valley and were quickly surrounded by the combined forces of local militias and a detachment of United States marines led by Robert E. Lee and J. E. B. Stuart. After a thirty-six-hour shoot-out, Brown and his surviving men surrendered.
At the insistence of Virginia governor Henry Wise, Brown was tried in state, not federal, court. At the end of a gripping trial held in Charles Town, he was found guilty of conspiracy, of inciting servile insurrection, and of treason against the state. He was hanged on December 2, 1859.
Brown's raid (and the fact that five of his "soldiers" were African Americans) touched off a frenzy among Southern slave-owners and, in the estimation of many historians, set the nation on an irreversible course toward the American Civil War (1861–1865).
Trumping the First Choice
The story behind the cover of this week's Book Review.
June 20, 2014, Friday
MORE ON JOHN BROWN AND: Allen, Jeffery Renard , McBride, James , McQueen, Steve , Brown, John (1800-59) , Jackson, Mitchell S , Books and Literature
Doctor, Teacher, Soldier, Spy
The curious and violent life of the abolitionist Dr. Rufus Gillpatrick.
December 18, 2013, Wednesday
MORE ON JOHN BROWN AND: Kansas , Slavery , Civil War (US) (1861-65) , State Legislatures , Cherokee Indians
Trading an African Dashiki for Union Blue
America's leading advocate for black emigration became an ardent recruiter for the Northern war effort.
October 4, 2013, Friday
MORE ON JOHN BROWN AND: Douglass, Frederick , Pittsburgh (Pa) , Immigration and Emigration , Civil War (US) (1861-65) , Slavery , Blacks
Newly Released Books
Novels and stories by Robert Boswell, Peter Orner, Kelly Braffet, James McBride, Aimee Bender and Saïd Sayrafiezadeh.
August 29, 2013, Thursday
MORE ON JOHN BROWN AND: Sayrafiezadeh, Said , Brown, John (1800-59) , McBride, James , Braffet, Kelly , Books and Literature , Bender, Aimee , Orner, Peter , Boswell, Robert
When Douglass Met Lincoln
What did the Great Abolitionist and the Great Emancipator discuss when they sat down at the White House?
August 9, 2013, Friday
MORE ON JOHN BROWN AND: Douglass, Frederick , Lincoln, Abraham , Stanton, Edwin M (1814-69) , Defense and Military Forces , Civil War (US) (1861-65) , Slavery , Blacks
The Price of Rebellion
Was my grandfather a hero for speaking out against Jim Crow racism? I'm not sure.
June 2, 2013, Sunday
MORE ON JOHN BROWN AND: Segregation , Discrimination , Virginia , King, Martin Luther Jr , Demonstrations, Protests, and Riots , Police , Civil Rights and Liberties , Blacks
Harpers Ferry, Redux
How John Brown's 1859 raid inspired a minister-turned-colonel to carry out a similar attack on Jacksonville, Fla. in 1863.
March 6, 2013, Wednesday
MORE ON JOHN BROWN AND: Brown, John (1800-59) , Higginson, Thomas Wentworth , Jacksonville (Fla) , Slavery , Civil War (US) (1861-65) , Blacks
The Forgotten Emancipationists
Recent popular history has overlooked the critical role of abolitionists in ending slavery.
February 24, 2013, Sunday
MORE ON JOHN BROWN AND: Lincoln, Abraham , Slavery , Emancipation Proclamation (1863) , Civil War (US) (1861-65)
America's Moral Volcano
American landscape painters engaged with the Civil War on a metaphorical level, none more so that Frederic Church's "Cotopaxi."
February 5, 2013, Tuesday
MORE ON JOHN BROWN AND: Church, Frederic , South America , Smithsonian Institution , Slavery , Civil War (US) (1861-65) , Volcanoes , Art
Well Before Lincoln, Enemies of Slavery
"The Abolitionists," a new three-part "American Experience" series on PBS, recounts the impact of five Americans, including Frederick Douglass and John Brown.
January 8, 2013, Tuesday
MORE ON JOHN BROWN AND: Slavery , Television , Stowe, Harriet Beecher , Garrison, William Lloyd , Brown, John (1800-59) , Douglass, Frederick , Public Broadcasting Service , Grimke, Angelina (1805-79)
Considering at John Brown
Photographs from two exhibitions.
Rss Feeds On John Brown
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Edy, I've seen the video before, but it was worth a second look---so much better it is than what passes for entertainment and humor today to entertains presidents and others. Did you notice how many laughs he got without talking dirty?
Don, busyness is a good way to keep grief at bay. I'm proud of you for keeping on "keeping on," though I know how very much you must miss Carol. I was thinking the other day how fortunate (or providential) for you that you know how to cook.
Blessings to all!


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Leave it to Carhartt to merge sweatshirt comfort with rugged work function. The venerable workwear company has a fleet of styles ready to keep you warm on the job and around town. Carhartt sweatshirts run the gamut of color and design, but come in two primary styles: Hoodies and Crewnecks.
Carhartt takes the classic cotton blend hoodie and crewneck styles to new heights. You will find zip and pullover hoodies lined with fleece for added warmth and adorned with 3M Scotchlite reflective taping to meet ANSI Class 2, Level 2 compliance. Carhartt's thermal lined sweatshirt is literally a jacket.
Carhartt has camouflage styles, high visibility blaze orange coloring and flame-resistant models to meet the demands of work and play. Although workwear has gained a popular casual appeal, Carhartt also makes dedicated casual styles with modern Carhartt logos and styles for men and women.
If no-nonsense sweatshirt style is what you are after, Altrec.com has a big selection of Carhartt hoodies and crewnecks.
We're Available:
Mon-Fri: 7:30am-4:00pm PST
Sat-Sun: CLOSED


text:
Game Questions & Answers (Q&A) service lets you ask questions about video games for game consoles or PC games. So ask your Gangstar: Miami Vindication HD question for IPad and get answers from real gamers or answer questions and share your insights and experience with the rest of the gaming community. Note: This apple iPad game app may also be compatible with the game app for apple iPhone.
- Developer: Gameloft
- Publisher: Gameloft
- Genre: Action General
- Release Date: Oct 26, 2010
- ESRB: Not Set
Stuck on this game? Set a specific, clearly defined question and let others answer your question or view answers to previously asked questions. If you think you are an Gangstar: Miami Vindication HD expert then please try to help others with their questions.
From: Confused
Posted On: 08-12-2011
Ask a Question
Please use our Search Box above to see if your question has already been asked, this will save you time waiting for answers which are already on the site.
Left In The Dark: No One On Board HD - Gameplay Review Trailer
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- Kim Kardashian: Hollywood - Gameplay, (Iphone-Ipod)
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- How To Train Your Dragon 2 - Ready To Fly Trailer, (Wii)
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- Munin - Official Launch Trailer, (IPad)


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From a self-described Non-Athlete, Mom:
--"I have not always been what I would call "athletic" but love the outdoors and being Active! I did my first supersprint on mother's day 2 1/2 years ago when my son was 6 months. Training and the goal gave me something to look forward to, and as a new mom, I really needed it." - GOTRIbal Member
From someone looking for connections to training partners around the globe:
--"I am super excited about the site, I have struggled trying to make connections in the sport, and getting training advice...so I am super pumped up. I was also drawn to the site, because in a few weeks my Husband and I will find out if we are moving out of the country and I didn't want to leave the sport behind. It would be so awesome to experience the Globalness of the TRIbe!" - GOTRIbal Member
From the self-described overweight, couch potato!
--"I was 233 lbs married to a drunk and a sad couch potato. Got rid of the drunk, lost the weight and other 'excess baggage' and started getting into shape. Addicted after my first triathlon actually addicted after I bought my first road bike to train. Thanks for the warm welcome." - GOTRIbal Member
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StartUpHire is the place to find Developer jobs in and near Novato. Review the list of Developer Novato career opportunities to the left. These Developer jobs represent some of the most rewarding careers available.
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Developer Jobs in Minneapolis, MN
We are looking for a talented, business-minded SFDC ninja to join our Sales Operations team, to help us continue on our successful journey.8/20/2014 San Francisco, CA Save This Job
Sauce Labs is looking for a Software Developer to join the team responsible for designing, building, & hacking out the Sauce Labs mobile cloud. Youâll work with both emulators & real devices and get yours hands dirty with Android, iOS, Python, & Node.jsFlexible Location: Vancouver, British Columbia and San Francisco, CA
About us: Twilio is providing a platform for building modern, communications-enabled applications that are cloud based, scalable, and focused on great user experience. More than 200,000 developers have signed up to be a part of this disruption, building everything from call7/22/2014 San Francisco, CA Save This Job
About Expect Labs: Expect Labs is a technology start-up based in downtown San Francisco. We are the creators of the MindMeld API, an advanced developer platform and cloud-based service to power a new generation of anticipatory computing applications. Our team is on a mission to8/18/2014 San Francisco, CA Save This Job
Location: San Francisco About Us: Twilio is migrating the communications industry from its 150-year-old legacy in hardware to its future in software. With our cloud communications platform, we fundamentally change how businesses build solutions for their communications8/21/2014 San Francisco, CA Save This Job
Your Job: As a Xamarin Developer Evangelist you'll be responsible for spreading the word about Xamarin to developers around the world, online and in person. Xamarin is growing FAST and needs social coders to help us reach and enable even more developers to build successful iOS8/3/2014 San Francisco, CA Save This Job
Are you passionate about software? Are you constantly pushing yourself to learn new technologies to develop better, faster and more efficient applications? Then CoStar is the place for you. Everyone at CoStar is deeply committed to delivering high-performing applications that9/8/2014 San Francisco, CA Save This Job
About Icontrol: Icontrol Networks? vision is to provide a connected home solution for every household, so people worldwide spend less time managing their lives and more time living them. Icontrol is making the connected home a reality through its software platforms, which are8/27/2014 Redwood City, CA Save This Job
Senior Android Application Developer Oakland, CA (Free shuttle from BART to the front door) Livescribe is in the midst of creating a series of mobile applications as well as an SDK for 3rd party application developers to connect with our award winning line of smartpens. We are8/12/2014 Oakland, CA Save This Job
Why are Developer Tools important at Airbnb? Our team takes pride in creating robust tools that enable our engineering team to do the best work of their lives. Solidly built tools enable us to move quickly and confidently as an entrepreneurial team. Fellow peers will experience7/29/2014 San Francisco, CA Save This Job
Job ID 772921 Location Danville, CA 94506 Other Location DescriptionJunior Application Developer Founded in 1995, iPipeline is the industry leader in SaaS-based software solutions for marketing, selling, and processing life insurance. Our vision is to continue to revolutionize7/28/2014 Danville, CA Save This Job
Reports To:Vice President of Product Development Status:Permanent or Contract Overview We are seeking an Embedded Systems Developer responsible for writing the firmware that drives the August Smart Lock. They will be responsible for customizing a Bluetooth LE stack,7/20/2014 San Francisco, CA Save This Job
Quantcast?s Enterprise Applications team seeks a talented Salesforce Developer to design and develop complex technical solutions in our highly customized Salesforce instance. Quantcast uses Salesforce extensively across all aspects of the company, including Sales, Campaign8/16/2014 San Francisco, CA Save This Job
Minimum Required Skills: Java EE, SQL, HTML5, CSS, AJAX, Networking SeeControl is seeking a Java Developer reporting to the CTO/VP of Engineering responsible for designing and developing the most advanced Internet of Things connectivity and applications platform in the world.8/16/2014 Redwood City, CA Save This Job
We have a team of very smart and talented software engineers working on our rapidly growing, highly successful mobile offerings. We need an experienced Senior Mobile Developer and to help us deliver a kick-ass experience to mobile users. About Us: While tweeting about the cute8/10/2014 San Francisco, CA Save This Job
About the Role: GSN Games is in search of a Senior Game Developer who is passionate about games and technology. As a Developer, you pride yourself on being a team player that can inspire and guide other developers in the group. If you like being challenged every day and8/10/2014 San Francisco, CA Save This Job
Are you an experienced, talented Drupal Developer that: is looking for a once in a life time opportunity to work on one of the nation?s major Drupal consumer sites that reaches over 70 million homes and tens of thousands of schools? is looking to work for an organization that8/4/2014 San Francisco, CA Save This Job
As a Java Server developer for Shaker, you will design and develop server-side code for web-based applications and the Shaker Platform. We are looking for experienced developer with a proven track record of delivering scalable and robust applications using web technologies. You8/2/2014 San Francisco, CA Save This Job
Plain Vanilla Games is looking for an experienced iOS developer to bring high quality features quickly and efficiently to QuizUp. The job includes implementing new features, improving legacy code and making sure QuizUp performs beautifully on the iOS platform. THE IDEAL7/30/2014 San Francisco, CA Save This Job
We are seeking a Senior Software Developer in Test to join our team in San Francisco to work on upcoming challenging projects. The engineer will be responsible for building on the existing WebService test framework along. They will be tasked with developing large scale WebService7/27/2014 San Francisco, CA Save This Job


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Hpro Ferrite Magnets - Silver Plated - 1000 Gauss
Directions for use
- Clean and dry the affected area.
- Apply piece by piece to the affected area.
- Keep on for at least 1 to 2 days and then change.
- Unnecessary to remove during bathing.Avoid continuous application to delicate skin for more than 24 hours.
- If itching, rash, or other irritation occurs, please transfer to another spot and apply a new one or discontinue use.
- For those with allergies or especially sensitive skin, it is advisable to refrain from using on the same spot continuously.
Weight (including packaging): 200g
Tax is not applicable to those living outside the European Economic Community. For more info click here.
99 in stock
Now: £3.25 (£3.90 inc. tax)
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The imminent threat of America falling over a "fiscal cliff" has been avoided, but Congressman John Fleming said the bill passed on Capitol Hill earlier this week did little to help the nation's biggest problem – rabid spending.
"Washington's spending addiction was given another shot Tuesday night," said Fleming, who was one of five Louisiana Republican congressmen to vote NO on the late-night measure. "I came to Washington four years ago on a promise to fight for less taxes, smaller government, and economic freedom. The bill that I voted NO on will increase taxes, allowing for more wasteful government spending and for a larger and more intrusive federal government."Subscribe to Read!


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Home Run Metal Sign
No longer available
- Overview
This old-school baseball park sign brings the feel of the field to your bedroom or lounge space.
- 36" wide x 20" high x 1" thick
- Made of metal.
- D-ring backing.
- Mounting hardware included.
- Dimensions + Care
- Wipe with a soft, dry cloth.
- Shipping Info
- Please allow 5-7 business days for delivery. Delivery estimate includes monogrammed and gift-wrapped items.


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Recent & Upcoming News
President's Message — July 2014
As the new President/CEO of your Credit Union, I'd like to take some time to introduce myself. My name is John F. King and I am the former Executive Vice President/COO of Freedom Credit Union. I have over 40 years of experience in the credit union movement and I am just as enthusiastic about it now as I was back then.
First, I would like to thank Lee T. MacMinn for his years of service and helping Freedom become the great place it is today. Working with Lee for 15 years was a great experience and I wish him the best in his retirement. I would also like to thank the Freedom Credit Union Board of Directors for entrusting me with the responsibility of growing the credit union and offering our valued Members the best financial products in the region.
My primary goal as the new President/CEO of Freedom is to continue in the cooperative spirit of "People Helping People." That is the true credit union difference. We, as Members, work cooperatively to help improve the lives of other Members. It's a motto that I've followed for my entire career and will continue to focus on as I take on my new role at Freedom.
Some of the areas where we plan on growing the credit union in the coming years, with your help, are in technology and lending. Offering Members technologically based products, such as the new Mobile Banking platform that we will introduce later in 2014, will make doing business with Freedom quick, easy and convenient which is a goal we have as an organization. We know that our Members' lives are busy, so we want to take away the stress of managing your finances.
Also, a primary goal is to save our Members more money. We have started a program where Freedom's outbound lending consultants may give you a call to save money on a loan that is elsewhere. If you have a loan at another financial institution, there's a pretty good chance we can save you money. The process can be done completely online with no need to visit our offices. Give us a call - I'm pretty confident we can help save you money each month but we won't know unless you give us a chance.
Members are the reason we exist. If we didn't have your participation in the Credit Union we would not be as successful as we currently are today. This is why it is important to me to know what you think about your credit union. So if you have any suggestions on how to improve Freedom Credit Union, please contact me. On behalf of the Board of Directors and the staff of Freedom, I personally want to thank you for your Membership.
John F. King, President/CEO
Refer New Members & Earn Cash!
For a limited time, when you refer a new Member to the Credit Union, and that person joins, you'll each earn $25!* We want to reward our new Members for choosing Freedom, and reward our existing Members for helping us grow. Plus, you get $25 for every new Member you refer.
To make a referral, just be sure that your friend or family member lives, works, worships, volunteers or goes to school in Southeastern PA, and ask them to include promotion code R8 when joining so that you both get your cash bonuses! New Accounts can be opened right away online-- just click here to get started.
* Promotion Code R8 and referring Member information must be provided. Cannot be combined with any other offer. A Joint Savings Account Owner age 18 or older is required for Members under 12. Each person can only be a new Member once. If eligible and in good standing, Referring and New Members' Primary Savings Accounts will each receive a $25 incentive by the 25th of the month after the new Primary Savings Account opened. The $25 incentive will be a taxable dividend on the 1099 Form we will send you in January. Offer is subject to change without notice.