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Men undergoing androgen deprivation therapy (ADT) lose muscle and strength and can also develop osteoporosis and other musculoskeletal problems. Findings from a small randomized trial published November 30 in the Journal of Clinical Oncology showed that a 12-week program that combined resistance and aerobic exercise was successful in improving strength, endurance, and quality of life in a group of men receiving ADT. Compared with 28 men receiving usual care, the 29 men in the exercise program increased their lean muscle mass, muscle strength, endurance, and balance, and reported better mental function and less fatigue and nausea. The exercise program had no effect on prostate-specific antigen (PSA) values, indicating "that combined resistance and aerobic exercise can safely be undertaken in patients with prostate cancer" receiving ADT, concluded the authors, led by Dr. Daniel A. Galvão from Edith Cowan University in Australia.
Trial Suggests New First-line Treatment Option for Slow-growing Lymphomas
Results from a phase III clinical trial conducted in Germany suggest that the standard initial treatment for patients with slow developing (or indolent) types of B-cell lymphoma should be changed.
The trial's lead investigator, Dr. Mathias Rummel of the University Hospital in Giessen, Germany, reported that patients treated with a combination of rituximab (Rituxan) and bendamustine (Treanda) lived significantly longer without their disease progressing and were less likely to experience major toxicities than patients treated with the standard first-line treatment, a four-drug chemotherapy regimen plus the monoclonal antibody rituximab called R-CHOP. Read more > >
Bone Drugs Linked to Fewer Cases of Breast CancerOral bisphosphonates tied to reduced incidence of the disease in separate studies
U.S. Cancer Cases and Deaths Continued to Decline in 2006Increased screening, reduction in risk factors, and improved treatments contributed to drop
Nilotinib Effective and Safe in Initial Treatment of Chronic LeukemiaDrug may be an alternative for patients who develop resistance to imatinib
Androgen Deprivation Therapy Linked to Cardiovascular Disease, DiabetesResearchers urge cautious use, additional research into risk and prevention of side effects
Antioxidant Supplement May Prevent Return of Precancerous Colorectal GrowthsLargest reduction seen in halting return of advanced adenomas
Director's Update: Modeling a Future without Cancer
Declines continue. When it comes to cancer rates, those two words are always encouraging. In fact, they were the headline attached to most news stories last week reporting the release of the 2009 Report to the Nation on the Status of Cancer. Understanding that this is not just a single year's trend, as the report made clear, but that many cancer rates have been on the decline for more than a decade, is particularly encouraging. Read more > >
Guest Commentary by Dr. Alan G. Thorson: Moving Toward a World with Less Cancer and More Birthdays
The president of the American Cancer Society shares his thoughts about past accomplishments and future efforts in cancer research Read more > >
Adapting the Science of Supplements and Cancer PreventionSmall clinical trials may provide clues about genetics, biomarkers, and maximizing preventive benefit
Putting Circulating Tumor Cells to the TestClinical trials are exploring new ways to use blood in oncology
Featured Clinical Trial: Defining Optimal Therapy for Metastatic and Recurrent Cervical CancerWhat is the best drug combination for metastatic or recurrent cervical cancer?
Cancer Center Profile: St. Jude Children's Research Hospital Comprehensive Cancer CenterThis is the nation's only NCI-designated comprehensive cancer center dedicated solely to pediatric cancers
- Fred Hutchinson Cancer Research Center to Operate NCI's CIS Contact Center
- Application Deadlines Approach for Interagency Oncology Task Force Fellowships
- President's Cancer Panel Examines Race and Cancer Burden
NCI Cancer Bulletin Publication Break
The NCI Cancer Bulletin will not be published on December 29. However, subscribers will receive via e-mail a list of the 10 most viewed articles from recent months. Our next issue will be released on January 12, when we resume our usual biweekly publication schedule. If you are not yet a subscriber, submit your e-mail address in the subscribe box above.
The NCI Cancer Bulletin is produced by the National Cancer Institute (NCI), which was established in 1937. Through basic, clinical, and population-based biomedical research and training, NCI conducts and supports research that will lead to a future in which we can identify the environmental and genetic causes of cancer, prevent cancer before it starts, identify cancers that do develop at the earliest stage, eliminate cancers through innovative treatment interventions, and biologically control those cancers that we cannot eliminate so they become manageable, chronic diseases.
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Featured Article
Trial Suggests New First-line Treatment Option for Slow-growing Lymphomas
Results from a phase III clinical trial conducted in Germany suggest that the standard initial treatment for patients with slow developing (or indolent) types of B-cell lymphoma should be changed.
The trial's lead investigator, Dr. Mathias Rummel of the University Hospital in Giessen, Germany, reported that patients treated with a combination of rituximab (Rituxan) and bendamustine (Treanda) lived significantly longer without their disease progressing and were less likely to experience major toxicities than patients treated with the standard first-line treatment, a four-drug chemotherapy regimen plus the monoclonal antibody rituximab called R-CHOP. Patients who received rituximab and bendamustine were also more likely to see a nearly complete disappearance of their disease (complete response) compared with the standard first-line treatment.
The findings were presented December 5 at the American Society of Hematology annual meeting in New Orleans.
A majority of the 549 patients in the trial had follicular lymphoma; most of the remaining patients had either indolent lymphoma or mantle cell lymphoma. The latter is a more aggressive lymphoma that is also typically treated with the R-CHOP regimen, Dr. Rummel explained. Trial participants had substantial tumor growth, complications from their disease, or a large tumor burden. "So [these were] patients in need of treatment, with defined indications for treatment," he said during a press briefing.
Among the 513 patients who were evaluated, the overall response rate—that is, the percentage of patients who experienced at least some tumor shrinkage following treatment—was very high in both groups, 92.7 percent in the bendamustine plus rituximab arm versus 91.3 percent in the R-CHOP arm.
However, in the longer-term, the two-drug regimen offered superior outcomes over R-CHOP. Median progression-free survival was 54.9 months versus 34.8 months, respectively, while the complete response rate was 39.6 percent versus 30 percent. Patients treated with bendamustine plus rituximab also had significantly lower rates of infections and of dangerous drops in white blood cells (WBC), and as a result they were much less likely to require treatment with granulocyte colony-stimulating factor to increase WBC production.
The trial was conducted primarily to see if the two-drug regimen was less toxic and equally as effective as R-CHOP, Dr. Rummel noted. "In the end," he continued, "we…demonstrated a clear statistically significant superiority of the better tolerated regimen."
Although he stressed that it can be important to have confirmatory results from another clinical trial, Dr. Richard Van Etten, director of the Tufts Medical Center Cancer Center, concurred with Dr. Rummel that these findings could alter the standard of care.
Some caution is warranted until longer-term data on toxicity are available, noted Dr. Anas Younes, a lymphoma researcher at the University of Texas M.D. Anderson Cancer Center, who made his comment in response to a reporter's question via Twitter.
Also, there are no overall survival data yet to report. But because these are slow-developing cancers deemed incurable, that may not matter in terms of defining the standard of care, explained Dr. Richard Little of NCI's Division of Cancer Treatment and Diagnosis. "It's very difficult in this disease to base standard-of-care decisions on overall survival," he said. "Most of the primary endpoint data that drives standard of care is based on progression-free survival, with significant attention paid to the treatment's toxicity." As a result, many clinicians may now favor the bendamustine-plus-rituximab regimen over R-CHOP in patients who require cytotoxic therapy, he said.
Dr. Rummel also stressed that the dose of bendamustine used in the trial is lower than what is indicated on the drug's label for use in lymphoma patients in the United States. The lower dose is critical in this case, he said, because it helps to avoid unnecessary toxicities without apparently compromising effectiveness.
Several proposals have been submitted to NCI for early stage clinical trials using bendamustine and rituximab in combination with other novel agents in patients with follicular lymphoma, Dr. Little noted, in the hope of further improving efficacy and reducing toxicity.
—Carmen Phillips
Cancer Research Highlights
Bone Drugs Linked to Fewer Cases of Breast Cancer
A new analysis from the Women's Health Initiative (WHI) study has found that the use of drugs called bisphosphonates, which are taken to improve bone health, was associated with a nearly 33 percent reduction in the incidence of invasive breast cancer compared with women who did not take the drugs. Although preliminary, the findings raise the possibility that this commonly used class of drugs may have a role in preventing breast cancer, researchers said at the 2009 CTRC-AACR San Antonio Breast Cancer Symposium.
Bisphosphonates are taken primarily for the treatment of osteoporosis but can also treat bone-density problems in patients with cancer-related conditions. Laboratory studies have suggested that these agents may also have anticancer effects, providing a possible biological explanation for the association.
To find the association, Dr. Rowan Chlebowski of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and his colleagues analyzed data on 151,000 women in the observational component of the WHI. Of the 2,216 women who were using bisphosphonates when they entered the study, 64 developed breast cancer, and most of those cancers (50) were estrogen-receptor positive.
The results translate into 32 percent fewer cases of invasive breast cancer among users of oral bisphosphonates—primarily alendronate (Fosamax)—compared with nonusers. A second study presented in San Antonio found a nearly 30 percent reduction of postmenopausal breast cancers among women in Israel who used bisphosphonates for at least a year compared with nonusers.
Since neither study was a randomized controlled trial, the results should be considered hypothesis-generating and are by no means proof, noted Dr. Leslie Ford of NCI's Division of Cancer Prevention and the institute's WHI liaison. "One issue is that women who take bisphosphonates often have low bone density because they are in a low estrogen environment," she said, "so these women would be at a lower risk for breast cancer than women who did not get bisphosphonates." This could be an alternative explanation for the result.
An ongoing clinical trial is looking at the role of bisphosphonates in the adjuvant treatment of breast cancer. If the results indicate that women taking the drugs have a lower rate of cancer in the opposite (contralateral) breast than women not taking bisphosphonates, this would "be a very intriguing finding and would make the current observations even stronger," said Dr. Ford. Nonetheless, randomized controlled trials in the preventative setting would be needed for this to become the standard of care, she added.
Bisphosphonates have been linked to osteonecrosis of the jaw, and the FDA issued a warning about musculoskeletal side effects of these drugs in January 2008. A year later, the FDA's Dr. Diane Wysowski warned of an increased risk of esophageal cancer and death in patients taking oral bisphosphonates.
U.S. Cancer Cases and Deaths Continued to Decline in 2006
The overall rate of new cancer cases diagnosed (incidence) and deaths from cancer (mortality) continued to decline significantly in the United States through 2006, due largely to lower lung, prostate, and colorectal cancer rates in men and lower breast and colorectal cancer rates in women. New diagnoses for all cancers decreased, on average, almost 1 percent per year between 1999 and 2006. Cancer deaths decreased 1.6 percent per year between 2001 and 2006. Researchers from NCI, CDC, American Cancer Society, and North American Association of Central Cancer Registries reported these findings in the Annual Report to the Nation on the Status of Cancer (1976-2006), published online December 7 in Cancer.
This year's report featured a special section on colorectal cancer (CRC) trends. Over the most recent data collection period, new cases of CRC fell 3.0 percent per year in men and 2.2 percent in women, while deaths from CRC fell 3.9 percent per year in men and 3.4 percent in women. Using data from NCI's SEER Program and the CDC's National Center for Health Statistics, the researchers used a microsimulation model, MISCAN-Colon, from NCI's Cancer Intervention and Surveillance Modeling Network (CISNET) consortium to estimate the impact of historical changes in modifiable risk factors (obesity, smoking, and diet), screening, and treatment on past CRC incidence and mortality trends and to project future mortality trends through 2020.
Of the 26 percent reduction in CRC mortality from 1975 to 2000, estimates from MISCAN-Colon modeling indicated that slightly more than half was due to increased screening (especially of older adults using the fecal occult blood test, sigmoidoscopy, and colonoscopy), more than a third was due to improvements in risk factors, and the remaining reduction can be attributed to better treatment. The model predicted a "36 percent overall decline in CRC mortality from 2000 to 2020 if current trends in risk factors, screening, and treatment continue," and, with accelerated cancer control efforts, "an overall mortality reduction of 50 percent by 2020 is possible," the authors wrote.
"The continued decline in overall cancer rates documents the success we have had with our aggressive efforts to reduce risk in large populations, to provide for early detection, and to develop new therapies that have been successfully applied in this past decade," said NCI Director Dr. John E. Niederhuber in a statement. "Yet we cannot be content with this steady reduction in incidence and mortality. We must, in fact, accelerate our efforts to get individualized diagnoses and treatments to all Americans and our belief is that our research efforts and our vision are moving us rapidly in that direction."
Nilotinib Effective and Safe in Initial Treatment of Chronic Leukemia
Preliminary results from a phase III trial testing nilotinib (Tasigna) against imatinib mesylate (Gleevec) as first-line treatment for chronic-phase chronic myelogenous leukemia (CML) indicate that nilotinib is effective and safe as initial treatment for this disease. The findings were presented December 8 at the 2009 American Society of Hematology annual meeting.
Imatinib has been a model for cancer drug developers because it specifically targets a mutant protein called BCR-ABL. Unfortunately, many patients eventually develop resistance to the drug, and this has led to the development of second-generation targeted therapies such as nilotinib and dasatinib (Sprycel) to treat imatinib-resistant CML.
An international group of researchers, led by Dr. Giuseppe Saglio of the University of Turin in Italy, enrolled 846 patients into the ENESTnd trial. Participants were randomly assigned to receive 300 mg of nilotinib twice daily, 400 mg of nilotinib twice daily, or 400 mg of imatinib once a day.
At 12 months of follow-up, patients receiving either dose of nilotinib had fewer white blood cells expressing the mutant BCR-ABL protein and were more likely to have no leukemia cells detected by laboratory techniques (a complete cytogenetic response) compared with patients receiving imatinib. Patients receiving nilotinib were also less likely to have their disease progress to an advanced stage.
Side effects and rates of drug discontinuation due to side effects were similar between the groups. Nilotinib is known to potentially cause problems with heart rhythm and function, but no severe cardiac side effects have been observed to date in the ENESTnd trial, Dr. Saglio reported. Although the investigators cautioned that the trial is still ongoing, the presenters suggested that nilotinib may eventually replace imatinib as the standard first-line therapy for CML.
Androgen Deprivation Therapy Linked to Cardiovascular Disease, Diabetes
Studies have indicated that older men receiving androgen deprivation therapy (ADT) for the treatment of prostate cancer may be at increased risk of cardiovascular disease and diabetes. A new study suggests that ADT can increase the risk of these side effects among all men undergoing this treatment.
To conduct the study, Dr. Nancy L. Keating of Harvard Medical School and her colleagues performed an observational study of 37,443 men treated with ADT through the Veterans Health Administration. The results appeared online December 7 in the Journal of the National Cancer Institute.
"Although the risks associated with androgen deprivation therapy remain incompletely defined, the potential for harm from this treatment underscores the importance of better understanding its benefits," the researchers concluded.
Of the 37,443 men, 39 percent received some form of ADT as part of their treatment. The majority of these men underwent treatment with a gonadotropin-releasing hormone (GnRH) agonist, a type of drug that blocks the body's production of testosterone. Only 0.8 percent underwent bilateral orchiectomy (removal of the testicles), 3.3 percent received oral antiandrogen monotherapy (treatment with a drug that blocks testosterone from binding to prostate cancer cells), and 4.9 percent received a combined androgen blockade (the combination of an antiandrogen monotherapy drug and a GnRH agonist). Patients with pre-existing cardiovascular disease or diabetes were excluded from the analyses, and factors such as cholesterol levels and statin use were taken into account.
Treatment with a GnRH agonist was associated with an increased risk of diabetes, coronary heart disease (CHD), heart attack, sudden cardiac death, and stroke. Combined androgen blockade was associated with an increased risk of CHD, and orchiectomy was associated with an increased risk of CHD and heart attack. Oral antiandrogen monotherapy alone, however, was not associated with an increased risk of any of the studied outcomes.
ADT has been shown to extend survival for men with locally advanced prostate cancer, but its benefits for men with less advanced disease are not clear, explained Dr. Peter C. Albertsen in an accompanying editorial. Despite this lack of clarity, its use in men with less advanced cancer has been increasing.
Antioxidant Supplement May Prevent Return of Precancerous Colorectal Growths
Long-term results from a clinical trial conducted in Italy suggest that an antioxidant compound may play a role in preventing colorectal cancer. In the trial, participants were randomly assigned to take a placebo or a selenium-based antioxidant compound supplement for 5 years following the removal of precancerous growths in the colon called metachronous adenomas. Participants who took the supplement had a statistically significantly reduced risk of adenoma recurrence compared with participants who took the placebo. The results were reported at the American Association for Cancer Research Frontiers in Cancer Prevention Research conference in Houston.
The reduction in risk extended out 13 years after participants had stopped taking the supplement, reported Dr. Luigina Bonelli of the National Institute for Cancer Research in Genoa, Italy, and colleagues.
There were 411 participants in the trial, and data on survival and the results of at least one total colonoscopy were available for 311 patients. The supplement used in the trial, manufactured by Pharma Nord, was a combination of selenomethionine, zinc, vitamin C, and relatively high doses of vitamins A and E.
Overall, participants who took the supplement had a 41 percent reduced risk of developing adenomas over the long term. Adenomas returned in 4.2 percent of patients in the supplement arm compared with 7.2 percent in the placebo arm. The reduction was especially pronounced in patients who had previously had advanced adenomas removed, which for this report included 111 participants in the antioxidant arm and 109 in the placebo arm. Among these participants, those who took the supplement had a nearly 90 percent reduction in the risk of developing advanced adenomas compared with those who took the placebo.
Regarding the clinical implications for these findings, Dr. Bonelli said: "We need further information to better target the treatment." Participants with prior advanced adenomas did appear to obtain the greatest benefit, she added, and there was little to no toxicity associated with the supplement.
The findings, while promising, have to be interpreted with some caution, noted Dr. Asad Umar, chief of the Gastrointestinal and Other Cancers Research Group in NCI's Division of Cancer Prevention. "Other data from observational and clinical trials examining the effect of selenium on colorectal cancer have yielded mixed results," showing either a decreased risk or no effect, he said. Selenium also appeared to have no effect in prevention trials for skin and prostate cancer, he added.
Director's Update
Modeling a Future without Cancer
Declines continue. When it comes to cancer rates, those two words are always encouraging. In fact, they were the headline attached to most news stories last week reporting the release of the 2009 Report to the Nation on the Status of Cancer. Understanding that this is not just a single year's trend, as the report made clear, but that many cancer rates have been on the decline for more than a decade, is particularly encouraging.
While progress against cancer—lower rates of new cancer cases and of cancer deaths—is welcome news at any time, I daresay none of us at NCI considers modest but steady progress to be sufficient. We must continue every effort to develop new understandings and comprehensive solutions to complex diseases. Yet, the report also makes a convincing case that we must work even harder to fully employ today's best methods of treatment and cancer risk reduction.
This year's report includes a special feature, which uses incidence and mortality modeling projections to show that colorectal cancer mortality could fall by as much as 50 percent by 2020 if many more Americans have regular colorectal cancer exams, exercise more, eat more healthily, and stop smoking, among other things. The potential benefit is stunning when you consider that it's estimated that colorectal cancer will take nearly 50,000 lives in the United States in 2009. Clearly, community-based programs of NCI and its partner agencies must even more strongly promote screening, improved nutrition, and smoking cessation.
In colorectal cancer, even applying today's adjuvant chemotherapy regimens to more patients could have a major impact. In their modeling efforts for the report, researchers assessed data on use of, and disease-free survival rates associated with, four chemotherapy regimens used to treat advanced colorectal cancer during different historical time periods. Just increasing conventional colorectal cancer treatment rates over time—from 8 percent of patients in 2005, to between 45 percent and 83 percent of patients by 2020—would have a significant impact on colorectal cancer mortality.
We often talk about a highly personalized approach to cancer research, patient diagnosis, and the development of biomarkers and targeted therapies, all tied to the unique cancer burdens of individuals. As this report strongly highlights, by applying some very straightforward actions that we know are effective today, and using them efficiently, we can make perhaps an equally large dent in the cancer burden. This will truly complement the benefit over the coming decade likely to be derived from targeted chemotherapy agents currently in the research and development pipeline.
For proof of that point, one needs look no further than lung cancer. Many have hypothesized that if we immediately got every smoker in America to quit, the overall death rate in the United States due to tobacco-related cancer could be cut in half.
There is one other area in which I have become convinced we have a great chance to dramatically impact cancer incidence and mortality: infectious agents. Current evidence indicates that as many as one in five cancers have an infectious cause. My belief is that with an increased effort, research addressing how viruses or bacteria can impact cancer causation may continue to give us significant opportunities to reduce incidence and mortality.
In fact, more than a dozen viruses already have been associated with various types of cancer. Researchers are still learning how a cell that is infected with a virus becomes a cancer cell. Hepatitis B and C have been linked to liver cancer conclusively and there are several cancers, including cervical cancer, that are associated with the human papillomavirus (HPV). Additionally, Helicobacter pylori has been linked to stomach cancer and several viruses have been associated with leukemia, lymphoma, and Kaposi sarcoma. Scientists are currently examining potential connections between some viruses and brain, colon, breast, and prostate cancer, although no definitive associations have been established yet for these diseases.
Identifying, treating, and even possibly preventing cancers caused by infectious agents such as retroviruses are ongoing challenges, because each virus causes cancer through a different process and some viruses cause cancer indirectly. Each day we are gaining a better understanding of the relationship between infection, immunity, and genetics. With this new understanding, we are beginning to develop new therapies and novel vaccines that target viruses, which could help lower the number of cancers that are associated with infections.
One of our great areas of promise in addressing the cancer burden comes from the intense study of the genetic and epigenetic alterations associated with the initiation and progression of cancer. The Cancer Genome Atlas (TCGA) project, a joint effort of NCI and the National Human Genome Research Institute, has been an extremely successful pilot that continues to unveil the genetic alterations, translocations, and mutations of a growing list of cancers. Using this comprehensive dataset may also provide unique insights into telltale signs of infectious agents.
During this past decade we have clearly broadened and deepened the tools that we have available to fight cancer. By effectively using these tools in the coming decade, we have an excellent opportunity to truly accelerate the rate of decline for many types of cancer. We are entering the second decade of the 21st century with a strong hope of reaching the goal of making many cancers chronic diseases, at worst, and memories of a bygone era, at best.
Dr. John E. Niederhuber
Director, National Cancer Institute
Moving Toward a World with Less Cancer and More Birthdays
The American Cancer Society held its 96th annual meeting last month in Los Angeles, where the Society's national volunteer and staff leaders gathered to conduct our annual business and to discuss ways that we can position ourselves for optimal delivery on our mission to save more lives from cancer.
This year, in addition to handling our required governance business, we had an extremely informative general session centered around the historic power and influence of women throughout the history of the American Cancer Society. From our legendary Women's Field Army to today's "mommy bloggers," women have helped deliver our mission in their role as the primary health care decision-makers in nearly all U.S. households. We examined how women are using their passion and power to transform the world around them and why, as we become a more constituent-focused organization, they are a critical market for the Society as it moves forward.
We culminated our meeting on the evening of Thursday, November 19, by bestowing our highest award, the Medal of Honor, on three distinguished scientists, Drs. Edward Harlow, Arnold Levine, and Marvin Zelen, and famed cancer survivor Lance Armstrong. However, a personal highlight was on Thursday afternoon, when I was inaugurated as the national volunteer President of the Society. The key to our ongoing success is the vital core of dedicated volunteers at the heart of the Society, who are relentless in their dedication to see an end to cancer. To that end, I am extremely humbled and pleased to represent the Society as its 2009–2010 President.
Our American Cancer Society enjoys unparalleled trust and confidence from the American public when it comes to cancer information and the ability to recommend what is the right thing for the country when it comes to health care reform. We have achieved that trust and confidence by bringing excellence to cancer prevention, treatment, research, and advocacy. Our American Cancer Society is respected because of its actions over the years: deliberate, cautious, in many ways predictable, science-based, and a voice for all cancer patients regardless of age, gender, race, ethnicity, sexual orientation, or political affiliation, because cancer respects no boundaries.
In my inaugural address I drew attention to the awesome task confronting our American Cancer Society in the coming year, to ensure that the integrity of, and trust and confidence in, our Society shall not be diminished. As we have worked to improve cancer prevention and the delivery of cancer care, we have learned much about the complicated process of trying to assimilate identified problems with health care delivery into the reality of health care reform. Our task in continuing this work is immense but our resolve steadfast. As we move forward, we recognize that the solutions to issues surrounding cancer prevention, treatment, research, and advocacy must be as uniquely American as is the public that provides our support.
As a global grassroots force of more than 3 million volunteers, the American Cancer Society fights for every birthday threatened by every cancer in every community. We save lives by helping people stay well through preventing cancer or detecting it early; helping people get well by being there for them during and after a cancer diagnosis; by finding cures through investment in groundbreaking discovery; by fighting back and rallying lawmakers to pass laws that will defeat cancer; and rallying communities worldwide to join the fight.
As the nation's largest non-governmental investor in cancer research, contributing about $3.4 billion, we turn what we know about cancer into what we do. As a result, about 11 million people in America who have had cancer and countless more who have avoided it will be celebrating birthdays this year. To learn more about us or to get help, call us any time, day or night, at 1-800-227-2345 or visit http://www.cancer.org.
Dr. Alan G. Thorson
President, American Cancer Society
Adapting the Science of Supplements and Cancer Prevention
Numerous studies suggest that avoiding excess weight, exercising regularly, and eating a diet heavy on fruits and vegetables decreases the risk of many diseases, including cancer. But as the expanding obesity epidemic has shown, there are major obstacles to getting broad swaths of people to adopt such a healthful lifestyle. So, for many years, cancer researchers have investigated whether specific nutrients—those that epidemiologic and animal model studies have suggested could sway cancer's course—could decrease cancer risk.
Much has been learned from this work, researchers in the field say, but, as is the case with treatment, each new discovery points to new areas of focus and other potential avenues of progress.
With promising bioactive compounds in the pipeline, many prevention researchers are focused on figuring out not just whether something like sulforaphane, a natural compound found in broccoli and broccoli sprouts, can kill cancer cells in a test tube or animal model—which it does, quite well—but how, at the molecular level, it accomplishes this task, whether there are some cancer cells that are more likely to respond to it, and whether there are ways of discerning early on that the intervention is having its intended effect.
Prevention: A Complex Matter
A number of supplements have been tested in large prevention trials, including vitamins A, C, and E; selenium; beta-carotene; and folic acid. At least one trial has demonstrated a reduction in cancer deaths with a combination of supplements, while several others found no reduction or even a small increased risk.
"There was suggestive evidence in humans" to support the large clinical trials conducted to date, said Dr. Peter Greenwald, director of NCI's Division of Cancer Prevention (DCP). Millions of people are taking supplements in the belief that they can improve their health, including preventing cancer, he continued, so getting data from randomized clinical trials—the gold standard of biomedical research—is critical.
But given the complexity of cancer, acknowledged Dr. Alan Kristal, a long-time cancer prevention researcher at the Fred Hutchinson Cancer Research Center, it raises questions about whether "high doses of micronutrients are going to have an impact on cancer risk."
And Dr. John Milner, chief of DCP's Nutritional Science Research Group, says that, in the pursuit of nutrition-based cancer prevention, it's more than just the complexity of cancer that has been underestimated. "In many ways, the lesson is that food and what we need to live is a lot more complex than we've ever thought," Dr. Milner said.
It's that complexity that researchers are increasingly tackling more directly.
Small Steps
At Ohio State University, Dr. Gary Stoner and his colleagues have been studying the cancer prevention potential of black raspberries for the last decade. Much of their work has focused on a powdered form of the entire berry, which eliminates the water that makes up 85 to 90 percent of the berry's weight.
The researchers began with laboratory and animal model studies, and when these studies demonstrated that the berry powder had prevention potential, they transitioned to small human trials. Some promising results have been seen in early stage human trials for esophageal, oral, and colorectal cancer prevention. A small skin cancer prevention trial is on the immediate horizon.
In the case of oral cancer, the Ohio State team worked with collaborators from the University of Kentucky to produce a berry powder-infused gel that is applied to precancerous oral lesions. Treatment for 6 weeks shrunk the lesions by as much as 50 percent and decreased the activity of genes related to cell growth and proliferation. Based on the results, NCI is funding a phase II, placebo-controlled trial of the gel.
"You can establish that something might work in a much smaller trial with a lot less money," Dr. Stoner said. "You can get a good idea if it will inhibit proliferation in a trial of 20 patients."
Small human trials, explained Dr. Kristal, can "integrate what's known about the carcinogenesis process and see whether we can manipulate that process with micronutrients or bioactive compounds." Even then, he stressed, they have to be carefully designed to ensure that they produce meaningful results that can potentially inform further studies and larger trials.
At UCLA's Jonsson Comprehensive Cancer Center, for instance, Dr. William Aronson is leading a phase II clinical trial of fish oil supplements, which are a plentiful source of omega-3 polyunsaturated fatty acids. The trial is randomly assigning men with prostate cancer who are scheduled to have their prostates removed to a low-fat diet with fish oil supplements or a standard Western diet for 4 to 8 weeks.
By analyzing tissue and blood samples taken before and after surgery, the researchers aim to determine whether the low-fat diet and fish oil combination alters the levels of certain serum and tissue proteins that may be associated with prostate cancer progression. "Such biomarkers may indicate that the intervention is working and will be an essential component of long-term human dietary intervention trials," Dr. Aronson explained.
Even here there are challenges, noted Dr. Kristal, because once potential biomarkers are discovered, it then has to be demonstrated that a change in a biomarker alters the course of the disease.
Both short-term trials and analyses of tissue samples from the large trials that have already been conducted may also help to address another critical issue: variability in response. "Any time you do a study, even with drugs, you don't get 100 percent effectiveness. You only get some people who respond," said Dr. Milner. "That's what happens with many nutrients as well."
All of this work, stressed Dr. Greenwald, is moving in the right direction to get these nutritional interventions into phase II and III trials. "If you have studies that clearly show an effect on biological endpoints that we think are related to cancer risk, a mechanism, and human data, that's very useful information," he said.
Moving Forward to Phase III Trials
While more early stage trials are on the horizon, those in the field agree that there will probably be somewhat fewer large phase III trials. One such trial, the VITamin D and omegA-3 triaL, dubbed VITAL, is set to begin enrolling the first of 20,000 planned participants in January 2010. The NCI-supported trial will test whether regular use of vitamin D and fish oil supplements, taken either alone or in combination, reduces overall cancer risk (as well as the risk of heart disease and stroke) in women aged 65 and older and men aged 60 and older.
"There is a narrow window of opportunity for doing a trial of this nature," said the study's principal investigator, Dr. JoAnn Manson, from Brigham and Women's Hospital and Harvard Medical School. Only in the last 2 years, Dr. Manson believes, "has the strength of the evidence for vitamin D and fish oil reached that threshold" to support launching a trial of this size. In addition, she argued, if researchers wait too long, "so many people could be taking [these supplements] that the trial will no longer be feasible."
Sales data on supplements support her concern. According to The Nielsen Company, sales of vitamins and supplements for June 2008 to June 2009 were up 5 percent over the previous year, totaling $1.5 billion. Vitamin D and fish oil are two of the biggest sellers.
VITAL researchers will analyze blood samples from a subset of participants to see if baseline levels of markers like 25-hydroxy vitamin D, the primary form of vitamin D circulating in the blood, and omega-3s correlate with reduced disease risk. And because the trial has a specific focus on recruiting a large number of minority participants, the researchers can analyze whether factors like participants' race or ethnic background influenced the response to the supplements and whether supplement consumption can reduce health disparities by race.
Advances may not come as fast as some might like, but they are happening, said Dr. Aronson. "I think we're going to make very significant progress over the next 5 years and we're going to gain important information that we can incorporate into larger trials."
—Carmen Phillips
A Closer Look
Putting Circulating Tumor Cells to the Test
Doctors have known for 140 years that tumor cells can escape into the blood of patients with cancer, and it has taken almost as long to find ways to capture these circulating tumor cells, or CTCs. But at least a dozen experimental tools for isolating the cells have emerged recently, creating new possibilities for using CTCs to understand how cancers spread and also to improve the care of patients.
To clarify the changing landscape and foster collaborations, NCI recently convened a meeting of cancer biologists, clinicians, and technologists—the people who develop the tools for capturing these elusive cells. More than 500 participants came to the NIH campus in September to hear presentations on cutting-edge technologies and exchange ideas about where the field needs to go.
The focus of the meeting was translational science—moving technologies from the lab to the clinic—and many presenters said that CTCs could play an important role in medicine. Doctors, they said, may one day be able to select treatments for patients and then monitor the effectiveness of those treatments simply by drawing and analyzing blood. In short, testing CTCs could be a kind of "liquid biopsy." There was also considerable interest in using the cells to learn about the metastases that cause most cancer deaths.
"Everybody understands how important research on these cells is; first and foremost, for patients, but also for other reasons, such as health economics," said Dr. Howard Scher of Memorial Sloan-Kettering Cancer Center, who presented at the meeting. "If doctors can use CTCs to tell patients that a drug is not going to work ahead of time, then you've spared the patients toxicity and allowed them to move on to something else."
But Dr. Scher cautioned that discovering and capturing these cells is only the first step. For CTCs to be used as biological markers for cancer, the prognostic value of these cells first needs to be validated, he continued, noting that the FDA has a path for biomarker development that has several stages similar to clinical trials for drugs.
FDA officials were at the meeting and gave presentations on the regulatory aspects of developing these new technologies, which are critical for moving the tools into the clinic, noted Dr. Avraham Rasooly of NCI's Division of Cancer Treatment and Diagnosis and the FDA Center for Devices and Radiological Health, who was one of the organizers.
The agency has cleared a technology called CellSearch for capturing and counting CTCs in patients with metastatic breast, prostate, and colorectal cancers as a prognostic tool. CTC counts above certain thresholds (five or more per sample in breast and prostate cancer; three or more per sample in colorectal cancer) are associated with a poor prognosis and may be an indication the disease is progressing.
Individualized Care
Many of the experimental tools in development are designed to go beyond prognosis and into the realm of personalized medicine. And for good reason: With a growing number of targeted cancer medicines, doctors want to know the genetic subtype of a patient's tumor, and this information could, in theory, come from CTCs.
"The future of targeted therapies in cancer is completely dependent on a patient's genetic profile, and you also need to be able to do serial monitoring of patients over time," Dr. Daniel Haber of Massachusetts General Hospital (MGH) said at the meeting. "When a patient stops responding to therapy, you need to know why and the principal mechanism of resistance."
His group, co-led by Dr. Mehmet Toner, a biomedical engineer at MGH, has developed the CTC-Chip, a microfluidic device that can capture CTCs from blood. (See movie above.) The team has shown, in principle, that they could use CTCs from the blood of patients with lung cancer to detect mutations in the gene EGFR, which are biomarkers for whether a patient is likely to respond to a certain type of therapy.
In another study, the group is asking whether CTCs can be detected in men with prostate cancer before the disease spreads. Currently, there is no way to identify patients at risk of relapse. The trial includes men whose cancers have not yet spread; their blood will be drawn before and after surgery, and then sampled periodically as the trial proceeds.
"If we could use CTCs to predict which patients are going to relapse, then doctors could consider additional treatments beyond surgery for those patients," said Dr. Sunitha Nagrath, one of the investigators.
In the Clinic
At the Lombardi Comprehensive Cancer Center at Georgetown University, Dr. Minetta Liu uses the CellSearch test in conjunction with routine imaging in her clinical practice. In a recent study of women with metastatic breast cancer, she and her colleagues found a strong correlation between CTC counts and radiographic evidence of the disease progressing. Their findings provide further evidence that counting CTCs in blood can predict the effectiveness of systemic treatments.
"We are all clearly interested in these cells, and patients are always eager for additional information about their health," said Dr. Liu.
Being able to assess a treatment's effectiveness from a simple blood draw could limit the number of time-consuming radiology studies a patient would have to undergo, she continued, while also providing additional reassurance about the effectiveness of a particular treatment regimen. Similarly, testing CTCs could prompt doctors to change treatments earlier than would be suggested by an imaging study alone.
This is important, Dr. Liu stressed, because for women with metastatic breast cancer the focus of treatment is to preserve an individual's quality of life. "In the absence of a cure, the ability to maximize treatment benefit and minimize toxicity and discomfort are of the greatest importance," she said.
Some patients may benefit from new therapies as their tumors evolve over time. A trial has just been launched to see whether CTCs can be used to identify women with metastatic breast cancer who are candidates for trastuzumab (Herceptin), even if previous tests did not suggest that they should receive the drug. Women whose tumors have abnormal levels of the protein HER2 are candidates for the drug.
"This trial represents a shift in the current thinking about how to manage metastatic disease," said the lead investigator, Dr. Massimo Cristofanilli of the University of Texas M.D. Anderson Cancer Center. Using a modified version of the CellSearch system, the study will not just count CTCs but try to use them as biomarkers to inform therapy by assessing HER2 expression in them, added Dr. Cristofanilli, who will soon join the Fox Chase Cancer Center.
"We may be able to offer what is very effective treatment to patients who wouldn't receive Herceptin because the primary tumor was HER2-negative," noted Dr. Jeffrey Smerage of the University of Michigan, another investigator in the trial.
The MagSweeper
At Stanford University, researchers are asking whether the analysis of CTCs can match patients and drugs early in treatment. The team will profile certain genes in CTCs using blood drawn from men with prostate cancer before and after they receive an experimental drug. As the trial progresses, it will be clear who the responders are, and the researchers will then look for associations with CTC gene profiles.
"We're trying to find out which genes are being expressed in the CTCs and whether they might help us choose a therapy," said Dr. Stefanie Jeffrey, a breast cancer surgeon at Stanford and a lead investigator of the study. "Hopefully, we'll be able to find out from the profile before patients are even on the drug whether they are likely to respond."
The trial is using a device called the MagSweeper to capture CTCs for analysis. As with so many of the technologies, Dr. Jeffrey developed the tool with a multidisciplinary team that included engineers and genome scientists. Some of their preliminary studies have suggested that not all CTCs are alike and that some may have characteristics of stem cells.
"I think we'll learn that this is a lot more complex than we initially thought based on our paradigm of cancer cells being shed by a tumor," Dr. Jeffrey said. "The field is just now burgeoning, and we still have a great deal to learn."
Dr. Thomas Ashworth, the Australian physician who observed CTCs in a patient with cancer in 1869, could not have foreseen where his discovery would lead.
"What's most exciting is that the technology is reaching a point where we can ask some questions, and trials are actually being done in multiple diseases," said Dr. Scher. The most important question, he added, may be: "How will testing CTCs help us make medical decisions?"
—Edward R. Winstead
Featured Clinical Trial
Defining Optimal Therapy for Metastatic and Recurrent Cervical Cancer
Name of the Trial
Phase III Randomized Study of Paclitaxel in Combination with Cisplatin or Topotecan Hydrochloride with Versus without Bevacizumab in Patients with Stage IVB, Recurrent, or Persistent Carcinoma of the Cervix (GOG-0240). See the protocol summary.
Principal Investigator
Dr. Krishnansu Tewari, Gynecologic Oncology Group
Why This Trial Is Important
Treatment options are limited for women with metastatic or recurrent cervical cancer. Currently, treatment of these women often includes chemotherapy with the drug cisplatin. Unfortunately, only up to one third of patients with metastatic and recurrent disease will respond to cisplatin-based chemotherapy, and these responses are short-lived, on the order of months. Additionally, because cisplatin-based chemotherapy (in combination with radiation therapy) is also used to treat patients with earlier-stage disease, recurrent cervical cancer may be resistant to additional treatment with platinum drugs. Therefore, doctors are trying to find alternative, non-platinum combinations for advanced disease that are able to shrink tumors and help patients live longer. Previous clinical trials have offered some promising leads, indicating that patients may benefit from treatment with the drugs paclitaxel and topotecan, as well as biological agents that target tumor angiogenesis.
A recent phase III trial of four cisplatin-based chemotherapy combinations in patients with advanced cervical cancer showed a trend toward better survival when cisplatin was combined with paclitaxel. The trial was stopped early, however, because none of the regimens appeared likely to provide a statistically meaningful benefit over the others, reinforcing the need for a non-platinum-based option. Topotecan combined with cisplatin has also demonstrated benefit in patients with advanced disease, but researchers suspect much of this benefit may be due to the effects of topotecan alone. These observations provide a rationale for pairing paclitaxel and topotecan, and a small pilot study demonstrated that the combination is safe and clinically active.
Antiangiogenesis therapy using the biological agent bevacizumab is also being investigated in women with advanced cervical cancer. Results of a phase II trial of bevacizumab alone, in women with persistent (refractory) or recurrent disease, showed the drug to be well tolerated and active.
In this phase III trial, women with metastatic, recurrent, or persistent cervical cancer that cannot be treated with surgery and/or radiation therapy will be randomly assigned to one of four treatment groups: paclitaxel plus cisplatin, paclitaxel plus topotecan, or either of these combinations with the addition of bevacizumab. Doctors will compare overall survival and the frequency and severity of side effects in patients treated with these regimens.
"Women with such advanced cervical cancer unfortunately have very few treatment options," said Dr. Tewari. "So, it's critical for them to explore clinical trials. This is the first randomized phase III study of a targeted agent in metastatic or recurrent cervical cancer, and it is the only U.S. phase III trial exploring the use of non-platinum combination chemotherapy in this patient population."
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.
Cancer Center Profile
St. Jude Children's Research Hospital Comprehensive Cancer Center
Director: Dr. Michael B. Kastan • 262 Danny Thomas Place, Memphis, TN 38105
Phone: 901-595-3300 • Web site: http://www.stjude.org
St. Jude Children's Research Hospital was established by the late entertainer Danny Thomas to provide treatment for children affected by catastrophic diseases, regardless of their race, religion, or ability to pay. Beyond their treatment, he wanted to build a hospital that would find cures and ways to prevent their diseases. In the late 1950s, Mr. Thomas and more than 100 others who had joined his cause formed the American Lebanese Syrian Associated Charities (ALSAC), the fundraising organization for St. Jude, and the hospital opened its doors in 1962. At that time, the 10-year event-free survival rate for the most common form of childhood cancer, acute lymphoblastic leukemia, was just 4 percent.
St. Jude has grown immensely since then. Today it employs a staff of more than 3,300 and has a daily operation budget of $1.4 million. The hospital occupies 2.5 million square feet of clinical, research, and administrative space, and about 5,700 active patients are seen at St. Jude yearly, most of them treated on a continuing outpatient basis as part of ongoing research programs. Patients are referred by doctors from all 50 states, as well as other countries. Clinical and research efforts still focus on cancer, but also include acquired and inherited immunodeficiencies, sickle cell disease, infectious diseases, and genetic disorders in children.
In 1977 St. Jude received its first NCI Cancer Center Support Grant. The hospital has been continually funded by NCI every year since then. It received special designation in 2008 as a Comprehensive Cancer Center, due to the combined disciplines of basic, clinical, and population-based research, and today it is the only NCI-designated comprehensive cancer center that focuses solely on pediatric cancers.
Among its list of achievements, the hospital boasts a faculty with renowned clinical and research staff, including recipients of the Nobel Prize and Albert Lasker Basic Medical Research Award. And because of research at St. Jude, the survival rates for numerous pediatric cancers have vastly improved; today the 10-year event-free survival rate for patients at St. Jude who are treated for acute lymphoblastic leukemia is more than 90 percent.
The Comprehensive Cancer Center at St. Jude includes several cross-disciplinary, multi-departmental programs dedicated to specific diseases (Hematological Malignancies and Neurobiology and Brain Tumor), conceptual themes (Signal Transduction and Molecular Oncology), or novel therapeutic approaches (Developmental Therapeutics for Solid Malignancies). The cancer center also includes a new Cancer Prevention and Control Program, which builds on the institution's commitment to long-term follow-up of patients in the After Completion of Therapy Clinic.
Cancer Center faculty members conduct a broad spectrum of research, including basic science research, investigation of disease pathogenesis and drug resistance, translational research, behavioral and quality-of-life research, and therapeutic trials. These research programs depend upon shared resources that are supported by the NCI Cancer Center Grant at St. Jude, including animal resources, biostatistics, cell and tissue imaging, cytogenetics, flow cytometry and cell sorting, the Hartwell Center for Bioinformatics and Biotechnology, pharmacokinetics, protein production, vector development and production, transgenenic and gene-knockout research models, and a Molecular Clinical Trials Core Facility.
Patient Care
The center emphasizes interdisciplinary research aimed at understanding, preventing, and treating childhood cancers. Most of the more than 400 children who are treated for cancer each year are enrolled in disease-specific, frontline protocols, and they are followed long-term to track their outcomes as they enter adulthood.
The cancer center at St. Jude is the home site for several ongoing national cancer studies, including the Pediatric Preclinical Testing Program, the Childhood Cancer Survivors Study, and the Pediatric Brain Tumor Consortium, all of which are funded by NCI.
Other Notable Programs
St. Jude recently completed an extensive expansion program that bolstered the hospital's research and treatment efforts, including the nation's only on-site pediatric research center facility that produces highly specialized treatments and vaccines; an expanded Department of Immunology; and a new Department of Chemical Biology and Therapeutics for the discovery of new drugs.
Also, the Chili's Care Center at St. Jude integrates patient care with research on evolving computerized tomography (CT) and magnetic resonance (MR) technology for radiation therapy, while a state-of-the-art cyclotron enables St. Jude researchers to undertake many new positron emission tomography (PET) radiochemistry studies. These imaging techniques help researchers and clinicians evaluate new therapeutic approaches quickly to determine those that are most likely to be successful.
Fred Hutchinson Cancer Research Center to Operate NCI's CIS Contact Center
On December 2, NCI selected the organization that will operate its Cancer Information Service (CIS) Contact Center. The program will be located at Fred Hutchinson Cancer Research Center in Seattle, WA, and will serve the United States, Puerto Rico, U.S. Virgin Islands, and the U.S.-associated Pacific Territories.
The contact center provides information to the public via the toll-free telephone number 1-800-4-CANCER, e-mail in English and Spanish, and LiveHelp instant messaging on NCI's Web site. The CIS is the federal government's source for the latest, most accurate cancer information for the public, patients and their families, and health professionals. For more than 30 years it has been providing up-to-date science-based information in easy-to-understand language. The center also provides smoking cessation counseling through NCI's Smoking Quitline, 1-877-44U-QUIT. The contact center handles over 100,000 inquiries annually and has responded to over 10 million callers since its inception in 1976.
Application Deadlines Approach for Interagency Oncology Task Force Fellowships
The Interagency Oncology Task Force (IOTF), a joint initiative between NCI and the FDA, has announced fellowship training opportunities for Ph.D.s, M.D.s, and M.D./Ph.D.s or their equivalents in cancer-related scientific research and research-related regulatory review.
The IOTF Joint Fellowship Program trains a core of scientists in cancer research and research-related regulatory review to develop skill sets that bridge the two distinct processes. During the program, fellows will:
- Build awareness of regulatory requirements into the early stages of medical product development
- Devise strategies to improve planning throughout the research and regulatory review phases
- Learn how to bring state-of-the-art knowledge and technology to bear on the design, conduct, and review of clinical trials
"We believe that physicians and scientists who are highly trained in the regulatory process, and who also have an understanding of the inner workings of NCI and FDA, will be able to facilitate and speed the development and approval process for drugs, especially for chemotherapy," said Dr. Jonathan Wiest, director of NCI's Center for Cancer Training.
Fellowship programs are available for various career levels and vary in length between 1 and 4 years. View each program's Web page for more information:
Clinical Oncology Product Research/Review for Oncology Fellows
Application deadline: January 31, 2010
Earliest start date: July, 2010
Clinical Oncology Product Research/Review for Board Certified (BC) Oncologists
Application deadline: January 31, 2010
Earliest start date: July, 2010
Oncology Product Research/Review Fellows
Application deadline: May 30, 2010
Earliest start date: September, 2010
Cancer Prevention Fellows
Application deadline: September 1, 2010
Earliest start date: July, 2011
The IOTF was established to enhance and accelerate the overall process of developing new cancer diagnostics and therapeutics and speed their delivery to patients. More information about the program fellowships can be found at http://iotftraining.nci.nih.gov.
President's Cancer Panel Examines Race and Cancer Burden
The President's Cancer Panel held the third meeting of its 2009–2010 series, "America's Demographic and Cultural Transformation: Implications for the Cancer Enterprise," on December 9 in Wilmington, DE. The panel heard testimony on differences in cancer burden, type, and causes across various races and ethnic groups. Speakers noted that racial categories were based on political constructs rather than biological fact and cited as evidence molecular differences in cancer that do not follow racial boundaries. Lack of access to care, inconsistent delivery of care, language barriers, and socioeconomic disparities were cited as major factors contributing to the unequal cancer burden. Speakers suggested the current approach to medicine based on racial categories negatively impacts patient health; speakers recommended moving towards a personalized approach to medicine based on the patient's individual history and risk factors, rather than on risk factors associated with a patient's race.
The panel will consider speaker recommendations in writing their 2009–2010 report to the President. The panel will hear additional testimony on the effects of the changing U.S. population on cancer care and research at their final meeting of the series in Miami, FL, on February 2, 2010.


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Right before Thanksgiving, a feast of turkey and more
Our daughter danced in socked feet, slipped to the hardwood floor
Busting open up her chin, seven stitches she bravely took
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Another... Read more
We were at the dinner table the other night, when the conversation turned surreal:
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My daughter came home with her usual bouncy, free spirited, attitude. She usually rolls through the door like an electrically charged ball, so when she flopped through the door with the daily spastic energy I'm used to, I didn't think to ask if anything could be wrong.
It's been a few weeks of this now, assuming things are going well, listening to her stories of school, until last week the little girl that usually sits by her on the bus chose to sit six seats back from my daughter. I asked her about it later that day, "Why didn't Liv sit with... Read more
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Wow, y'all. Was that a week or what?
The week started out as usual. Monday morning came with the... Read more
Nobody wants to hear you wax morose about the things in your life you'd change. It's not a very good blog post. It's a much better bartender story. Bartenders are trained in that sort of thing: Indecision, Regret, Wondering.
The Internet as a whole, not so much.
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I'm so busy being a "jack of all trades" that I haven't narrowed down my one passion. I'm so.. passionate… that I haven't figured out where to concentrate that passion on.
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I never had headgear. I never had braces. I never had extreme acne. No, my Jr. High experience was flanked with sports and friends and the usual self consciousness. High school was a stable place with a boyfriend and good grades and more sports.
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I've had a package, two actually, sitting in my living room for SIX MONTHS that I need to mail. It contains time sensitive materials. They are full of clothes for my sister's daughter, I think you call that my niece, and my good friend's daughter.
It's literally been six months and I doubt they will fit their children anymore.
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My son had a field trip the other day to a cabin in the woods. It's a cabin from 1865, a simpler time, were the butter was only made because you made it yourself. The cabin was cold. (As you'd expect old cabins to be.) We pondered life in the old days and how different things are now.
Maybe it's a sign of the... Read more
My young son sat on the log outside waiting for snack. The older kids poured out from the Kindergarten room and I see his eyes follow a little blonde girl. He stands up, runs to her and says, "I'm here, Piper!" The little girl, Piper, doesn't hear him. She has another friend of ours talking to her and my young son is standing behind her. "Here, Piper, I'm here!" I hear Piper ask where he is and finally she hears him, the third time, and turns around. "Oh! There you are! I missed you!" She sits down and pats the seat next to her. My son... Read more


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Ithaca College is committed to providing high quality benefits programs that give you the options and flexibility you need at work and in life. Benefits are an important component of the total compensation package offered by the College. Our goal is to offer Ithaca College employees the most comprehensive benefits plan possible. With Individual Choice, the College's flexible benefit program, you have the power to make your benefits even more valuable — because you can choose features that fit your individual needs. This valuable program is enhanced by your ability to choose the benefits you need. By selecting wisely, you create a benefits package for yourself and your family that is truly an Individual Choice.
Individual Choice
The Individual Choice Program includes benefits such as medical and dental insurance, life insurance, accident insurance, and long-term disability coverage.
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Ithaca College's educational benefit program consists of three types of benefits: (I) tuition remission for employees taking courses at Ithaca College; (II) tuition remission for dependent children, and spouses or qualified domestic partners attending Ithaca College; and (III) cash awards for dependent children attending another college or university. These benefits are applicable to tuition only and do not apply to room, board or any fees.
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The popular web search engine that spawned a tech empire is now old enough to get a learner's permit Friday.The website celebrated with a special interactive banner that they call Google Doodles that starts with a birthday cake and ends with the player using the spacebar or mouse to hit a piñata. The goal is to get as much candy out as possible.The search giant also has a special Easter Egg that allows users to see how they looked 15 years ago by searching the term "Google in 1998."The exact birth date of Google has shifted around over the years, but they were founded on Sept. 4, 1998 by Larry Page and Sergey Brin, both Ph.D. students at Stanford University.Google celebrated its birthday a day early on Thursday by announcing that they have once again reworked their algorithm. In a unveiling ceremony in the Menlo Park, Calif. garage where it all started, Page and Brin unveiled "Hummingbird" which has been slowly been rolled out over the past month.
The Associated Press contributed this article
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Justin Halpern and Brian Huntington of Grantland.com put together a "scientific" infographic of what The Ultimate Awful Quarterback would look like. It's a compilation of bad traits of past and present NFL QBs. It's quite entertaining and can be found here .
As a Minnesota Vikings fan, I've been subjected to many an awful quarterback in my time. So, I thought I'd do something similar with quarterbacks who have donned purple and horns during their career.
Minnesota has had some truly terrible quarterbacks throughout their 50-plus years in existence. Don't get me wrong, they haven't all been bad. Their first ever quarterback, Fran Tarkenton is in the Pro Football Hall Of Fame. As is, Warren Moon. He played for the purple from '94-96 before breaking his collarbone and losing his job to Brad Johnson. Daunte Culpepper was pretty good for Minnesota, nearly winning the MVP Award in 2004. Then, the following year his entire career came crashing down after tearing his knee to shreds halfway through the season. Brett Favre. Loads of good and bad traits with that guy. The good, being that he's almost guaranteed to be inducted into the Hall of Fame. The bad, we'll get to that soon enough.
Without further ado, the Ultimate Awful Vikings Quarterback:
We'll start at the top of our fictional signal-caller. The head. More specifically, what's inside the head. The knowledge, decision-making and composure of the worst Viking quarterback have got to go to, Joe Webb. Webb has all the athletic talent you could ever ask for. But, when it came time to shine and fill in for an injured Christian Ponder during last year's Wildcard playoff game against the Packers in Lambeau, Webb reacted by completing only 11 passes on 30 attempts. I recall one of those passes going straight up in the air. Yikes.
Staying somewhat in the head, but also including the arm is Christian Ponder. You always hear about how great his healthy arm is (was). Rarely have fans ever seen such a display from Ponder. He holds onto the ball like a swaddled little baby that he doesn't want to ever let go. Just throw the damn ball, man!
The hands are next on my list. This was the easiest to come up with. Hands down, (excuse the pun) this one is all Daunte Culpepper. For having such a massive frame, (6'4" 260lbs.)he has the hands of a carnival worker. His tiny, almost malformed hands contributed to 40 fumbles in less than 10 years of actual playing in the NFL. I bet he smells of cabbage too.
The legs have to go to, Kelly Holcomb. Remember that crappy quarterback? He only played in 3 games for Minnesota during the 2007 season. He never even attempted to run the ball with Minnesota. This wasn't a bad idea considering he averaged less than a yard per run throughout his illustrious career.
The feet were tough to come up with. Minnesota has had more than a handful of immobile, statuesque players under center. Sean Salisbury, Brad Johnson, Gus Frerotte, Jeff George, Brett Favre, and the list goes on. But I went with, Tavaris Jackson. Sure, T-Jack was mobile when he decided to run. What makes him the Vikings QB with the worst feet is the fact that he rarely kept them on the ground as he threw the ball. Way too many of his throws were jump-passes that were more times than not picked off. You always hear analysts talk about proper footwork. Jackson had little to none.
Age was another hard trait to settle on. Minnesota loves bringing in old dudes to play football. Jim McMahon was 34 when he signed with the Vikes. Warren Moon turned 38 during the first of three seasons with Minnesota. Randall Cunningham was well past his prime when he put on a purple jersey at the age of 34. In fact, he was out of the NFL for a year before the Vikings brought him in to be their starter. Fresh off a 15-1 record during the 1998 season the Vikes had a pair of ancient quarterbacks to put in the game the next year. At 32 years old, Jeff George was brought in to backup an aging Randall Cunningham. The QBs on the roster during that 1999 season had an average age of 33. The next year they drafted Daunte Culpepper. But, by far the most youth-challenged quarterback has to be, Brett Favre. The guy was 42 when he retired from football as a member of the Vikings. 42! He was the epitome of a dirty old man at this point. Getting into trouble for sending lewd voicemails and his crotch pics to co-workers.
And with that, the Ultimate Awful Vikings Quarterback.
Agree or disagree? Hit me up on Twitter @cade1037
*image courtesy of: Pixabay.com


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CVS Health Colleagues
By being hired into one of our Project Management jobs at CVS Health, you'll be a key member of the CVS Health team. Professionals in Project Management careers come from a variety of backgrounds, bringing an assortment of knowledge and skills to every area of our business. Please click on your desired Project Management job below to learn more about the exact qualifications. A job in Project Management at CVS Health may be waiting for you!
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Staying healthy isn't easy these days. Health care costs keep rising. People are overwhelmed and confused by all the changes. They're looking for help. They're looking for solutions that make a difference. At CVS Health, we know that to make a difference, you have to do things differently. So we're reinventing pharmacy to help people on their path to better health.


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So, not sure what this thing is all about??? It's quite simple, create a quick page with Brandi's Hayes Page Kit and you'll receive an album back full of quick pages made by each of the participants. Check out our QP Exchange Gallery to see what the participants have created.
Each participant will submit at least 1 quick page but not more than 2 using this kit only. At the end of this exchange, all participants will receive all submitted quick pages including a special one created by Brandi.
* Layouts should be created and saved at 12" x 12" and 300ppi.
* If you are familiar with creating a quick page in a transparent .png file, please submit it in that format.
* If you are not, we have a couple of tutorials to help you in this area: Paint Shop Pro & Photoshop
* If you are unable to create a .png file, please design your quick page by creating your layout and using a white or black area (whichever is of most contrast to your layout) for the photo placements. Save your layout as a flattened .jpg file at full resolution (unless you are submitting a png file already) . I will take what you submit and punch out the areas for photos and convert them to transparent .png files before sending them all back to the participants.
* Please name your files as follows to help me track these easier. YourForumName_KitName_QP.png so as an example, mine would be brandiwest_hayes_QP.png.
* Save a preview of your quick page at 600x600 and upload it to the Quick Page Exchange Gallery for all the oooohs and ahhhs!
* Holly will need the preview .jpg at 600x600, and either the .png or .jpg file at the full 12x12 size sent to me. You may use any file sharing site of your choice, or you can zip it up and email Holly the zip at firstname.lastname@example.com.
* Sign-ups are required for this so that we know who is working on pages.
* You may submit up to 2 quickpages for this challenge.
* I will keep this post updated to reflect participants and whether files have been received.
* The submission deadline for this round is end of the day on Thursday, June 22nd. Please be sure to send me the files by that time as well.


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Rancho RS5000 steering stabilizers reduce steering shimmy, improve tire control, and give you more control over your vehicle if a tire should blow out. The single stabilizers protect front-end suspensions and are used with tires up to 35 in. tall. Dual stabilizers are for off-roaders with tires 35 in. and taller.
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PLEASE NOTE this product requires a Mac Allister 36V battery sold separately. See EANs 5052931161744 & 5052931161751. The Mac Allister 36V lawnmower offers cordless operation, grass collection & lots of features making mowing a pleasure. With 6 different cutting heights 25-75mm and a 35cm cutting width suiting medium sized lawns up to 350m2 (19x19m). An indicator alerts when the 40L grass collection box is full & the integrated display panel indicates different cutting modes and battery level.
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titus young
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i think the latriots need this guy bad. he could ve our jacoby jones for less money. the patriots need to get him now


text: BFN. I have no words. I'm so freaking disappointed. What is my body doing!? Why have my cycles been fairly regular until I actually need them to be? CD32 and counting... I should have stayed home from work today... I've been here 12 minutes, and have already almost cried. I just wish AF would come so I could move on and stop holding on to apparently pointless hope.


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Today's clogs are as advanced as any casual shoe on the market and bear little resemblance to the wooden clogs of old. Clogs and "slides," as many models are known, offer all-day comfort and a versatile, relaxed appeal and, of course, they are as easy to put on as they are to take off. We offer a full variety of slide-in footwear for work and informal occasions from full-leather professional styles to beachwear.
The all-day comfort and good looks of a Dansko clog is unmatched in professional looking footwear. Waiters, waitresses, nurses and doctors all over the country choose Dansko clogs for their professional style, all-day comfort and durable leather construction. Whether you are looking for a nursing clog or a sharp but relaxed look for the office, Dansko shoes will serve your feet well, day in and day out.
When the occasion calls for the ultimate in relaxed footwear, look to our wide variety of slides from Crocs, Merrell, and Keen. Merrell offers all-leather slides for men and women and even makes sheepskin lined slides for cold weather comfort. Crocs offer their trademark fully-molded Croslite construction to create an incredibly lightweight, yet comfortable and functional clog. Kids love Crocs for everyday wear, and you know you will too.
Step into something a little more sophisticated with a clog from Finn Comfort. Their full-grain leather construction and orthopedic support combine to make shoes that promote comfort and foot health - and look great, too. Finn Comfort footwear is designed with casual beauty and the health of your feet in mind. They make the perfect clog for informal gatherings and daily wear.
Finally, how can we discuss clogs without mentioning an early standard in comfortable footwear, the Birkenstock Boston clog. This timeless classic offers closed-toe comfort for men, women and kids. Birkenstock's footbed is famous for its pronounced arch support, deep heel cup and roomy toe box. Birkenstocks offer a classic, casual look for almost any affair.
The bottom line is that we offer a clog or slide for every occasion. Clogs and slides are far more than limited casual wear. They are excellent everyday footwear designed with comfort and foot health in mind.
We're Available:
Mon-Fri: 7:30am-4:00pm PST
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Women's Apparel
Showing all 4 results
Womens Pirate Polo$23.95
Girlie Skull$21.95–$24.95
Emerson Knives exclusive : Girlie Skull featuring a pink skull and logos on both front and back sides. Fitted closely to the body, a flattering fit! Available in sizes S-2XL
Women's Hell & High Water$18.95–$21.95
This is a classic Emerson Brand T-Shirt featuring the new, "Famous in the Worst Places," slogan. This is a whiskey drinkin', hard fightin' style you can be proud to wear anywhere.
Womens Gunslinger Gear T-Shirt$21.95
The Fallen Angel is the ultimate symbol of good having given in to the pleasures of sin. Women's Gunslinger Gear T-Shirt available in sizes S-XL. Custom designed by Emerson Apparel.


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Home > Party Themes > Pirate > All
Red Beverage NapkinsItem: 203-439
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Celebrate in Style
Brighten up any party table with our solid color tableware. The perfect accessory for any table. No matter what your event, we have the color you need!
- 20 napkins per package.
- Solid red napkins.
- 5″ long and wide.
- Two-ply paper napkins.
Add something extra to any table, our tableware is just what you are looking for. Something fun and functional for any party. This red tableware is perfect for Graduation parties, Christmas, Valentine's Day and Patriotic events.
Reviewed By:Paula
Sioux Falls, SD
Great Color
we are holding a very special ribbon cutting event for our remodeled office and we were a little nervous about ordering red from a website. The red in the plates and napkins we ordered was PERFECT! We are thrilled!


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Monthly blind tasting notes
2005 William Fevre Chablis 1er 'Montee de Tonnerre' – citrus, mineral and menthol hints in the nose, and a sweet impression in midpalate, but a clean dry finish.
1999 Jadot Beaune 1er – good colour, a nose that could be pinot but could be something else – it didn't shout out it's 'pinot-ness'. Smooth wine with slightly high acidity, drinking well.
2002 Dom. Ch. de Chorey Beaune Vignes Franches VV – slight warmth in this sweet Ribena nose, along with some spice. Full bodied, ripe and enjoyable.
2002 Ch. La Martine Cahors Cuvee Particuliere – 90% Malbec and 10% tannat, this was a serious wine with dark colour, ripe sweet nose of spice and currant, tons of soft tannin and a nice lingering finish. Good show.
1996 Teldeschi Petite Sirah Dry Creek – a stalky cab style nose and as big well structured wine left us guessing just about anything BUT PS. Decent wine, no rush.
1999 Sean Thackrey Orion Old Vines – Another poser as it showed a dark wine with huge sweet slightly tarry nose with a metallic (not bad) notes. It was sweet and a tad simple in the mouth, well structured and medium long. I wonder what this will do with a bit more time?
1999 Kenwood Jack London Cabernet – vinyl hints in the nose of this fairly dark wine, resolved tannin, decent fruit and medium length. OK, but nothing like the old style Jack Londons. Everyone though this wine was significantly older than the next wine that I poured – they wouldn't have made that mistake with an old JL!
1992 Beringer Private Selection Cabernet – sweeter riper mocha blackberry nose much more attractive (to me, anyway) than the Kenwood, a smooth entry into a wine with significant soft tannin and tons of flavour, with good length. I liked this a lot, which is a good thing, as this is the first bottle of a half case I have that I've opened since I bought it on release. No rush, at peak now. I have this in 91, 92, 93 and 94 – a vertical may be in order.
2004 Rivera Castel del Monte Puer Apuliae – made from Nero di Troia (add one more grape to my life list) the wine was still purple at the edges with a nose of sweet cassis, and great legs. Sweet fruit on palate and mellow in the mouth despite significant tannin. Lots of flavour concentration at the end. Interesting and meritorious wine.


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Since 1876, the Banks Lyon family name has been synonymous with the finest quality luxury watches and jewellery from some of the world's most prestigious brands, from Cartier and Omega watches to Chopard, Fope and CARAT* jewellery. A look around the website will give you a hint of the extensive collections of exclusive products we carry, both in our watches and jewellery categories. Banks Lyon's success has been founded on the peerless advice and friendly service we give to each and every one of our customers.
We pride ourselves on offering a personalised service to everyone, whether that be in our Lancaster based showroom or over the phone. We strongly believe that purchasing a luxury watch or piece of jewellery should be a memorable experience and, as such, we are here to help that be the case.
In addition to stocking Omega watches, Cartier watches, Breitling watches and Bremont watches, we also stock Chopard watches, TAG Heuer watches, Armani watches, Gucci watches, Tissot watches and a wide range of jewellery. Our high-street showroom on Church Street, Lancaster carries a large stock-holding of luxury watches and jewellery which you are welcome to come and browse in person. We also operate a comprehensive watch repair and valuation insurance service for any of the brands we sell, ensuring you and your purchase are well looked after both now and in the future.
We supply loose, GIA and Antwerp Certificated Diamonds direct from the Diamond Bourse in sizes ranging from 0.30 carat to over 10.00 carats in traditional Brilliant cut or any fancy cut you may desire.
This website illustrates just some of the varied stock we carry, while our latest products can be seen here. If you fail to see something of interest please contact Rodney at firstname.lastname@example.com who will be pleased to source any item and answer any questions you may have.
Rodney Banks-Lyon FGA, NAG Dip and his experienced colleagues are always available to deal with your enquiry, whether it be simply asking about a battery change and reseal of your watch or the commission of a fabulous piece of Diamond jewellery. In fact, whatever your enquiry, our team are here to assist you with it.


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Whether you're traveling on business, a leisure getaway, or a family vacation, La Quinta has the right hotel accommodations for you. Take advantage of free Internet access, free breakfast, and comfy beds offered at La Quinta Inns & Suites. You'll find the best rates online, the widest variety of room options, the most reliable hotel info, and more on LQ.com. Thank you for considering La Quinta Inns & Suites for your hotel travel plans!


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This greenhouse shelf kit provides a simple storage solution for greenhouses. It's hanging system saves floor space and it can be easily repositioned depending on your needs. Includes two shelf parts, brackets and fixing screws. Clamps to the aluminium frame inside any polycarbonate greenhouse.
*Free delivery over £50 refers to home delivery orders placed on diy.com only. Charges refer to the value of goods being delivered and excludes delivery from stores or services. Excludes bulk delivery.
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