National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
November 13, 2012 • Volume 9 / Number 22

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NEWS

Study Shows Importance of Early End-of-Life Care Discussions

Elderly woman in a hospital bed Patients with advanced cancer who discussed end-of-life care with their doctors earlier in the course of their illness had care that was less aggressive in their last month of life and were more likely to use hospice services, according to a new study. Earlier discussions may help to ensure that care at the end of life is more consistent with patients' preferences, the study authors explained. Yet, on average, these discussions took place about 1 month before a patient died, they found. 

The study was published online November 13 in the Journal of Clinical Oncology (JCO). Read more > >

MULTIMEDIA

A MESSAGE TO READERS

Special Issue on the Science behind Cancer Screening

Don't miss our November 27 special issue, which will focus on the science behind cancer screening. In addition to commentary from some of the top experts in cancer screening, articles will look at addressing disparities, translating clinical trial findings into practice, and using modeling to determine who will benefit most from screening.

Past special issues have focused on oncology nursing, obesity and cancer research, and adolescent and young adult cancers

IN DEPTH

UPDATES

  • FDA Update

    • New Treatment Approved for Chronic Myelogenous Leukemia
  • CDC Update

    • Global Study Documents Tobacco Use, Secondhand Smoke Exposure among Women of Childbearing Age
  • Cancer.gov Update

    • Newly Launched NCI Map Stories Show Geographic Patterns of Cancer
  • Notes

    • National Cancer Advisory Board to Meet Later this Month
    • NCI Workshop Will Address Scientific Priorities for Cancer Epidemiology
    • CancerCare, NCI Seek Submissions for eHealth Video Challenge
    • Cancer Research Network Scholars Program Accepting Applications
    • Quit Smoking with Mobile Resources from NCI

Selected articles from past issues of the NCI Cancer Bulletin are available in Spanish.

The NCI Cancer Bulletin is produced by the National Cancer Institute (NCI), which was established in 1937. Through basic, clinical, and population-based biomedical research and training, NCI conducts and supports research that will lead to a future in which we can identify the environmental and genetic causes of cancer, prevent cancer before it starts, identify cancers that do develop at the earliest stage, eliminate cancers through innovative treatment interventions, and biologically control those cancers that we cannot eliminate so they become manageable, chronic diseases.

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

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

Featured Article

Study Shows Importance of Early End-of-Life Care Discussions

Elderly woman in a hospital bedPatients who discussed end-of-life care earlier were less likely to receive aggressive care and more likely to receive hospice care.

Patients with advanced cancer who discussed end-of-life care with their doctors earlier in the course of their illness had care that was less aggressive in their last month of life and were more likely to use hospice services, according to a new study. Earlier discussions may help to ensure that care at the end of life is more consistent with patients’ preferences, the study authors explained. Yet, on average, these discussions took place about 1 month before a patient died, they found. 

The study was published online November 13 in the Journal of Clinical Oncology (JCO).

Although some patients may wish to have aggressive care at the end of life, "most patients who recognize that their cancer is terminal want to receive less-aggressive care," the study's lead investigator, Dr. Jennifer Mack of the Dana-Farber Cancer Institute, said in a news release.

The American Society of Clinical Oncology and other groups recommend that discussions about palliative and end-of-life care begin shortly after a patient has been diagnosed with advanced cancer. Several studies have found that such discussions between physicians and patients with advanced cancer are often delayed until late in a patient's life, if they take place at all.

For example, an earlier study by Dr. Mack and her colleagues found that oncologists had end-of-life care discussions with only about one-quarter of their patients, and, when the end-of-life care discussions took place, they often happened in the hospital during episodes of acute care.

In the new study, researchers analyzed patient (or patient surrogate) interviews and the medical records of more than 1,200 patients with end-stage lung or colorectal cancer regarding discussions about end-of-life care, including resuscitation and hospice care. All patients in the study lived for at least 1 month after diagnosis and were participants in the NCI-funded Cancer Care Outcomes Research and Surveillance Consortium.

Almost half of the patients had at least one form of aggressive care in the last month of their lives: 16 percent of patients underwent chemotherapy within the last 2 weeks of life, 40 percent received acute care in the hospital within the last 30 days of life, and 6 percent were treated in the intensive care unit in the last 30 days of life.

Most patients who recognize that their cancer is terminal want to receive less-aggressive care.

—Dr. Jennifer Mack

Patients who had end-of-life care discussions earlier, however, were much less likely to receive aggressive care and more likely to receive hospice care.

The results "really highlight that much more work needs to be done to address this long-standing problem," said Dr. Ann O'Mara, a program director in NCI's Division of Cancer Prevention who leads the institute's palliative care research program.

In a March 2012 interview with the NCI Cancer Bulletin, Dr. Thomas Smith, director of palliative care for the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, noted that discussions about palliative care should begin shortly after diagnosis, even with patients who do not have a terminal cancer. However, these discussions are particularly important for patients with incurable cancers, he said.

"Most [oncologists] choose not to have discussions about things like hospice, do-not-resuscitate [orders], and advance medical directives until there are no more chemotherapy options left," he said. "That allows us to avoid a hard conversation, but it doesn't serve as well to prepare the patients and families for what's coming."

Less-aggressive care near the end of life can clearly benefit patients and their families, Dr. Mack commented.

Aggressive end-of-life care has been linked to a higher risk of depression among caregivers after the patient has died, she explained. And for patients, less-aggressive care can mean "a better quality of life in their final days, because there is a greater focus on symptom management and they are more often able to receive care in their homes," she said.

Now that several studies (for example, here and here) have documented that earlier palliative care can improve patients' quality of life and, in some cases, may have improved survival, Dr. O'Mara believes the time is ripe for "an intervention trial that examines the timing and frequency of doctor-patient conversations and the impact they have on patients and families," particularly with regard to care decisions and their psychosocial impact on family members and caregivers.

Carmen Phillips

This research was supported by grants from the National Institutes of Health (U01 CA093344, U01 CA093332, U01 CA093324, U01 CA093348, U01 CA093329, U01 CA093339, and U01 CA093326).

Further reading: "Last Days of Life" and "Palliative Care Improves Survival, Quality of Life in Advanced Lung Cancer"

Cancer Research Highlights

Drug May Reduce Cognitive Decline Following Radiation for Brain Metastases

A drug already approved to help improve cognition in some patients with dementia may limit declines in memory and cognitive function in patients who are undergoing whole-brain radiation therapy (WBRT) to treat cancer that has spread to the brain. Results from a clinical trial to test the drug, memantine (Namenda), in patients with brain metastases were presented October 28 at the American Society for Radiation Oncology (ASTRO) annual meeting.

More than 60 percent of patients with brain metastases who undergo WBRT experience problems with cognitive function within 4 months after completing treatment, explained the trial’s lead investigator, Dr. Nadia Laack of the Mayo Clinic Cancer Center, during a press briefing. The intent of the NCI-supported trial was to determine whether memantine could prevent memory decline in patients, rather than to test whether the drug improved progression-free or overall survival, Dr. Laack noted.

The phase III randomized trial, conducted by the Radiation Therapy Oncology Group and dubbed RTOG-0614, enrolled more than 550 patients, who received either memantine or a placebo during WBRT and for 6 months afterward. The researchers assessed participants’ memory and other cognitive functions, such as the ability to process information and make decisions, before and after treatment. Many patients in the trial died or had cancer that continued to progress, however, so after 24 weeks only 149 patients could be evaluated.

Patients whose disease progressed “often refused testing so, in effect, we were largely evaluating patients who had not progressed,” Dr. Laack explained in an e-mail message.

In patients treated with memantine, memory decline took longer to appear and was less severe, although the improvement was not statistically significant. However, the risk of cognitive decline fell 17 percent, a drop that was statistically significant.

“Although memantine was discontinued at 6 months, the effect on cognitive function was maintained for the duration of the trial, suggesting that memantine may be preventing radiation injury rather than simply treating cognitive dysfunction,” Dr. Laack said.

Based on the trial’s results, memantine will likely now be used as standard therapy for patients undergoing WBRT to treat brain metastases, she added. “We do feel that this is going to impact practice tomorrow and that, for future trials, memantine will be the standard against which other agents are tested.”

This study was funded in part by the National Institutes of Health (CA21661, CA32115 and CA37422, RTOG U10 CA21661, and CCOP U10 CA37422).

Brazil's Strong Antismoking Policies Credited with Saving Lives

Using a policy simulation model called SimSmoke, researchers have estimated that strong tobacco control policies implemented in Brazil between 1989 and 2010 cut the smoking rate nearly in half and saved almost 420,000 lives during that period. Dr. David Levy of Georgetown University's Lombardi Comprehensive Cancer Center and his colleagues published their findings November 6 in PLOS Medicine.

Using SimSmoke, the researchers looked at the effects of various tobacco control policies on the smoking rate in Brazil, which declined from 34.8 percent in 1989 to 18.5 percent in 2008. SimSmoke models the effects of tobacco control policies on smoking initiation and cessation rates and uses the changes in these rates to estimate smoking rates over time. 

The Brazil SimSmoke model showed that almost half of the 46 percent reduction between 1989 and 2010 was due to tobacco tax and price hikes. Smokefree air laws, restrictions on advertising, programs to help people quit smoking, media campaigns, and mandatory health warnings on tobacco packaging also contributed to the drop in smoking rates.

“This study indicates how powerful tobacco control policies are,” said Dr. Levy.

Brazil’s current tobacco control policies are projected to reduce the smoking rate from 16.8 percent in 2010 to 10.3 percent in 2050 and prevent an estimated 7 million premature deaths due to smoking. The model also showed that, if Brazil fully implemented policies recommended by the World Health Organization’s Framework Convention on Tobacco Control, the country’s smoking rate would fall to 6.3 percent by 2050, preventing 1.3 million more deaths. 

“Brazil’s accomplishments demonstrate that, even for a middle-income nation, reducing tobacco use is a ‘winnable battle’ that carries huge dividends in terms of reducing mortality and morbidity,” the researchers wrote. 

“There is now a ‘global laboratory’ of tobacco control,” said Dr. Michele Bloch, acting chief of NCI’s Tobacco Control Research Branch. “Studies from around the world allow countries to benefit from each other’s experience.”

This study was funded in part by the National Institutes of Health (UO1-CA97450-02).

Possible Cause of Doxorubicin-Induced Heart Damage Identified

The damage to heart tissue (cardiotoxicity) sometimes seen with the drug doxorubicin may be caused by the chemotherapy’s effects on an enzyme called topoisomerase-IIβ (Top2β). This finding, from experiments in mice led by Dr. Sui Zhang of the University of Texas MD Anderson Cancer Center, was published October 28 in Nature Medicine.

The results suggest that Top2β is “an essential driver of doxorubicin-induced cardiotoxicity,” the authors concluded. This knowledge could lead to the development of drugs that are less cardiotoxic than doxorubicin, as well as to tests that identify patients who are most at risk for heart damage associated with this drug, they said.

Doxorubicin’s anticancer effects are thought to be caused by its interactions with a related enzyme, called topoisomerase-IIα (Top2α). This enzyme is expressed in rapidly dividing cells, including cancer cells, but not in mature, nondividing cells. Top2β, on the other hand, is found in all cells, and the highest levels are found in mature cells.

Because doxorubicin also interacts with Top2β, the researchers proposed that the drug might damage mature heart muscle cells through its effects on this enzyme. For their experiments, the researchers genetically engineered mice to have heart muscle cells that did not express Top2β. 

When normal mice were exposed to doxorubicin, the researchers found changes in the gene expression of heart-muscle cells that were not found when mice with Top2β-deficient hearts were treated with the drug. Many of the changes occurred in cellular signaling pathways that regulate cell death (apoptosis) and the functioning of mitochondria, structures inside cells that produce most of the energy cells use.

When researchers measured the level of apoptosis in heart muscle cells to assess doxorubicin-induced damage to the heart, Top2β-deficient hearts had 70 percent fewer dying heart muscle cells than normal hearts after doxorubicin treatment. Moreover, mice with Top2β-deficient hearts had no decrease in heart function after 5 weeks of doxorubicin, whereas heart function in normal mice fell by 10 percent.

Drugs that specifically target Top2α and not Top2β “should be less cardiotoxic and, hence, more useful clinically,” they continued. And measuring Top2β expression could identify patients more likely to experience heart damage from doxorubicin. “These predictions can be tested in animals and humans,” they concluded.

This study was funded in part by the National Institutes of Health (CA102463).

Study Reveals New Mechanism of Action for Class of Targeted Therapy

Researchers have discovered a new way in which PARP inhibitors block cancer cell growth. The researchers also have found that three experimental PARP inhibitors, which were presumed to have similar activities, vary widely in their ability to kill cancer cells. The study, led by Dr. Yves Pommier of the Laboratory of Molecular Pharmacology in NCI’s Center for Cancer Research, was published November 1 in Cancer Research.

PARP inhibitors have shown promising anticancer activity against breast and ovarian cancers in women with BRCA1 or BRCA2 gene mutations. The drugs were believed to block cancer cell growth by inhibiting the activity of PARP proteins, which help repair damaged DNA. Therefore, drugs with similar levels of PARP inhibition should have comparable anticancer effects. However, studies have indicated that treating cells with a PARP inhibitor causes more toxicity than would be achieved simply by loss of PARP activity, suggesting that these drugs may have a second mechanism of action.

The researchers showed that PARP inhibitors can also trap PARP proteins at sites of DNA damage, forming PARP-DNA complexes that are toxic to cells. The strength of the trapped PARP-DNA complexes correlated with a drug’s ability to kill cancer cells and varied widely between the three tested PARP inhibitors, which are currently being studied in clinical trials.

“While PARP inhibitors had been assumed to be of equivalent potency based on the degree to which they elicit PARP inhibition, we now know that they are not equivalent with respect to their potency to trap PARP,” said Dr. Pommier in a news release.

The new study also showed that PARP inhibition and PARP trapping are not directly related. Olaparib (AZD2281) was the most potent PARP inhibitor followed by veliparib (ABT-888) and then niraparib (MK-4827).

In contrast, cells treated with niraparib or olaparib formed the most potent PARP-DNA complexes. When combined with a DNA alkylating agent, niraparib and olaparib also were much more toxic to cancer cells than veliparib.

“Our findings suggest that clinicians who use PARP inhibitors in clinical trials should carefully choose their drug, because we now suspect results may differ, depending upon the PARP inhibitor used,” said first author Dr. Junko Murai, in a news release.

The researchers also investigated the effects of these PARP inhibitors on 30 cell lines that had different DNA repair genes inactivated. The results confirmed that cells without BRCA1 or BRCA2 function are more sensitive than normal cells to PARP inhibition. The study also revealed other genes not previously implicated in sensitizing cells to PARP inhibitors. These results may help determine which tumors are most likely to be susceptible to PARP inhibition.

This work was supported by NCI's Intramural Research Program.

Also in the News: Radium-223 Improves Survival in Men with Metastatic Prostate Cancer

Final data from a trial involving men with castrate-resistant prostate cancer that had spread to the bones showed that radium-223 (Alpharadin) improved overall survival by more than 3 months. Radium-223, part of a class of drugs called alpha-particle emitters, targets bone metastases.

The final results from the ALSYMPCA trial were presented October 28 at the American Society for Radiation Oncology annual meeting.

Overall survival in the final analysis of the trial was 14.9 months for men who received radium-223 compared with 11.3 months for men who received a placebo, a slight improvement over the findings of an interim analysis presented earlier this year.

Men treated with radium-223 also lived nearly 40 percent longer without having a skeletal-related event, such as a bone fracture or spinal cord compression, or the need for radiation therapy to treat symptomatic bone metastases.

Also in the Journals: Genetic Factors Linked to Lung Cancer in Asian Women Who Have Never Smoked

Researchers have identified three more regions of the genome that may play a role in the development of lung cancer in Asian women who have never smoked. One variant is on chromosome 10 and two are on chromosome 6. The study also confirmed previous reports linking regions of chromosomes 5, 3, and 17 to lung cancer in Asian women who have never smoked.

Women with one of the three newly identified genetic variants may be more susceptible to lung cancer caused by environmental exposures, including secondhand smoke, the researchers found, although this needs to be replicated in other studies. Contrary to previous research, this study found no evidence that a variant on chromosome 15 is associated with lung cancer in Asian women who have never smoked, which suggests that this variant may be smoking related.

The genome-wide association study included data from 14 studies and compared the genomes of 6,600 Asian women with lung cancer and 7,500 without lung cancer. Dr. Qing Lan of NCI’s Division of Cancer Epidemiology and Genetics and her colleagues published their findings November 11 in Nature Genetics.

This study was supported by the National Institutes of Health (ZIACP010121).

Multimedia

NIH Research Radio: A Clinical Trial for HIV-Positive Cancer Patients

Health provider reviewing paperwork with two clinical trial participants

NCI Cancer Bulletin writer and editor Daryl McGrath talks about a phase II clinical trial exploring the safety of stem cell transplants for HIV-positive cancer patients

audio icon Click to Listen

Type: (MP3) | Time: 5:00 | Size: 5.7 MB | Read Transcript

Special Report

Decades Later, Chernobyl Accident Yields Clues to Leukemia Risk

Historical photo of Chernobyl nuclear power plant cleanup workers (Courtesy of Dr. Victor Kryuchkov, Burnazyan Federal Medical Biophysics Center)Studies of cleanup workers from the Chernobyl nuclear power plant have revealed a link between ionizing radiation and chronic lymphocytic leukemia. (Photo courtesy of Dr. Victor Kryuchkov, Burnazyan Federal Medical Biophysics Center)

Exposure to low doses of ionizing radiation over extended periods of time may raise the risk of chronic lymphocytic leukemia (CLL), as well as other types of leukemia, later in life, new research suggests. The findings are from a study of Ukrainian workers who were exposed to radiation while cleaning up the 1986 Chernobyl nuclear power plant accident.

Twenty years after the disaster, these workers, as a group, had an increased risk of CLL and other forms of leukemia, researchers reported online last week in Environmental Health Perspectives. The case-control study used information from a larger study tracking the health of more than 110,000 Chernobyl cleanup workers.

"Previous research has shown an increased risk of some types of leukemia related to radiation exposure," said lead researcher Dr. Lydia Zablotska of the University of California, San Francisco. "However, none of those studies have reported an association for CLL, so we were intrigued by our findings."

In the new study, Dr. Zablotska's team attributed 19 of 117 cases of leukemia (16 percent) diagnosed in the cleanup workers since the Chernobyl nuclear reactor accident to radiation exposure from the accident. The magnitude of risk was similar for CLL and for other types of leukemia.

CLL is more common than other leukemias in the United States, with some 15,000 cases diagnosed last year. The disease is a relatively benign leukemia, but some patients require chemotherapy and the cancer can be fatal.

In addition to providing clues about the causes of CLL, the new findings could help researchers understand the long-term health effects of exposure to low-dose radiation. "The radiation burden in the United States has increased over the past 20 years, primarily from exposure to CT scans," said Dr. Zablotska. "We want to know what this radiation can do in the long term." 

More recent photo of Chernobyl nuclear power plant with monumentTwenty years after the disaster, researchers continue to monitor the health of those exposed to radiation from the Chernobyl accident.

Radiation can cause damage to DNA that eventually leads to cancer. Studies of atomic bomb survivors have documented the cancer risks associated with short-term exposure to moderate and high doses of radiation. Less is known, however, about the health effects of exposure to lower doses of radiation over a longer period of time, such as the doses experienced by the cleanup workers.  

In 2008, the research team first reported an association between radiation exposure and CLL in Chernobyl cleanup workers. Because the finding was unexpected, the authors undertook the current study with a larger sample and longer follow-up.

"For researchers, these findings are exciting because they could open up new research into the mechanism of how CLL develops," said Dr. Kiyohiko Mabuchi, who heads the Chernobyl Research Unit in NCI's Division of Cancer Epidemiology and Genetics and is the senior author of the new study.

He noted that other studies of radiation-exposed workers have not detected an increased risk of CLL, so more research is needed to understand these inconsistencies. Identifying the biological mechanism underlying the association will be important, he added.

This study provides "some of the most substantial evidence to date supporting the conclusion that developing CLL is a possible adverse consequence of exposure to ionizing radiation," noted Dr. David Richardson, an epidemiologist at the University of North Carolina, Chapel Hill, who studies the health effects of radiation but was not involved in the research.

"It will be important to continue to monitor health consequences," added Dr. Mabuchi, "both in cleanup workers, as well as in other groups exposed to radiation from the Chernobyl accident."

Edward R. Winstead

This research was supported by NCI's Intramural Research Program.

Featured Clinical Trial

Dietary Intervention for Patients Receiving Chemoradiotherapy for Lung Cancer

Name of the Trial
Phase I Trial of a Ketogenic Diet with Concurrent Chemoradiation for Non-Small Cell Lung Cancer (KETOLUNG; NCT01419587). See the protocol summary.

Drs. Sudershan K. Bhatia and Douglas R. Spitz Drs. Sudershan K. Bhatia and Douglas R. Spitz

Principal Investigators
Drs. Sudershan K. Bhatia, Daniel James Berg, John Michael Buatti, and Douglas R. Spitz, University of Iowa Holden Comprehensive Cancer Center

Why This Trial Is Important
One of the fundamental differences between cancer cells and normal cells is in how they break down (metabolize) nutrients to obtain the energy they need to grow and survive. Normal cells typically rely on oxidative metabolism of glucose, fatty acids, or amino acids to produce energy. In this process, which takes place inside cellular structures called mitochondria, chemical reactions that require oxygen are used to maximize the amount of energy produced from each molecule being metabolized.
 
Cancer cells, on the other hand, have defects in mitochondrial oxidative metabolism, leading to excess production of potentially harmful molecules known as reactive oxygen species. This can create a condition called metabolic oxidative stress. To compensate for this defect in mitochondrial metabolism, cancer cells use mitochondrial oxidative metabolism, as well as another metabolic process called glycolysis, to break down glucose.

Cancer cells are believed to use much more glucose than normal cells because, in addition to using it for energy production, cancer cells can use the products of glucose metabolism to detoxify reactive oxygen species. Researchers are exploring ways that this difference in cellular metabolism between cancer cells and normal cells might be exploited to selectively kill cancer cells.

Carbohydrates in the diet provide a readily available supply of glucose that can be used to fuel cancer cell growth. Therefore, one method being investigated is the use of a specialized diet that dramatically reduces the amount of glucose in the blood, called a ketogenic diet. This type of diet has been used for decades to help children and young adults with treatment-resistant epilepsy that causes grand mal seizures.

Ketogenic diets are so named because they force the body into a starvation-like state called ketosis, in which the liver converts fats into molecules called ketones that circulate in the blood and can serve as mitochondrial energy sources for certain tissues. Ketogenic diets, therefore, restrict the amount of glucose available to cancer cells and force them to rely more heavily on oxidative metabolic pathways that might selectively induce oxidative stress in cancer cells.

"We're interested in a ketogenic diet for cancer therapy because it limits glucose metabolism and emphasizes oxidative metabolism of fatty acids, ketone bodies, and amino acids in mitochondria. We think that mitochondria from tumor cells produce more superoxide and hydrogen peroxide [two types of reactive oxygen species] than mitochondria from normal cells," said Dr. Spitz. "Consuming a ketogenic diet should therefore selectively enhance the sensitivity of tumor cells to treatments that increase oxidative stress, such as radiation and chemotherapy."

Radiation therapy is thought to kill cancer cells by generating free radicals that cause oxidative stress, and this can be enhanced by the simultaneous use of chemotherapy (chemoradiation). "If oxidative stress is selectively enhanced in cancer cells by the ketogenic diet, the reactive oxygen species produced by the radiation and chemotherapy can more effectively damage DNA, proteins, and other critical biomolecules in the cancer cell and improve cancer cell killing, as well as improving therapeutic outcome," he explained. 

In this phase I clinical trial, patients with stage III or IV (with limited metastasis) non-small cell lung cancer who are about to undergo chemoradiation therapy will consume a ketogenic diet for the duration of their treatment. Doctors will assess the safety and tolerability of the diet in conjunction with chemoradiation treatment, as well as measure the levels of glucose and ketones in the blood and oxidative stress markers in plasma and urine.

About 90 percent of calories in the ketogenic diet used in this study come from fat, whereas less than 2 percent of calories come from carbohydrates, with protein supplying the remaining calories. Participants will consume specially formulated shakes in the morning and work with a dietician to maintain a similar calorie balance throughout the day. They will begin the ketogenic diet 48 hours before the initiation of chemoradiation therapy and continue through the end of the 6- to 7-week treatment period. 

"An excellent example of the role of increased glucose metabolism in cancer is the FDG-PET scan," said Dr. Bhatia. "We use PET scans with all of our lung cancer patients as part of our diagnostic and staging tests. At a fundamental level, the PET scan is done using glucose with a radioactive tag (18F-FDG) injected into the patient, and that glucose lights up the area of tumor cells because of their metabolic pathway. That's how we determine where the tumor is and, in metastatic disease, where the cancer has spread. With this diet, we hope to deprive the tumor of the glucose it depends on for energy as well as enhance oxidative stress."

This study, as well as a similar study for pancreatic cancer patients, is being conducted at the University of Iowa's Holden Comprehensive Cancer Center.

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

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

Community Update

DREAMing Big to Solve Cancer Research Challenges

DREAM logo

Earlier today, at the DREAM7 Conference in San Francisco, representatives from the two best-performing teams in the NCI-DREAM Drug Sensitivity Prediction Challenge took to the stage to unveil their methods. Members of the two teams, from Helsinki, Finland, and Dallas, TX, along with 50 other teams from around the world, spent several months this year putting their heads together to work on two related scientific challenges.

NCI-DREAM is part of a larger project known as DREAM (Dialogue for Reverse Engineering Assessments and Methods). Now in its seventh year, DREAM is one of a growing number of biomedical research endeavors that take advantage of crowdsourcing—outsourcing a task to a group or community through an open call or contest.

NCI partnered with DREAM to support innovative approaches to cancer research and to capitalize on the breadth of knowledge of the research community to develop better treatments for cancer patients.

Crowdsourcing "takes advantage of the strength of the broader community to expand our understanding of some difficult scientific problems," noted Dr. Dan Gallahan, deputy director of NCI's Division of Cancer Biology and one of the organizers of the NCI-DREAM challenge.

"The project was born to try to help the research community understand the limitations and strengths of our own methods," explained Dr. Gustavo Stolovitzky, an IBM computational biologist who has been a driving force behind the project. "Crowdsourcing also allows us to determine what the best method is for the solution that we are seeking."

Solve This!

Participants in the two-part challenge were asked to use a vast array of genomic information to build computer models that can predict the sensitivity of cancer cell lines to a set of small-molecule compounds or combinations of compounds. The goal of sub-challenge 1 was to predict the sensitivity of 18 breast cancer cell lines to 31 previously untested compounds, while the goal of sub-challenge 2 was to predict the activity of pairs of compounds on a diffuse large B-cell lymphoma (DLBCL) cell line.

Two researchers working together on a problemParticipants in the NCI-DREAM challenge spent several months working with their teammates on two related scientific problems.

Genomic data for NCI-DREAM were provided by Dr. Joe Gray of Oregon Health and Science University and Dr. Andrea Califano of Columbia University.

"Drug sensitivity prediction from genomic profiles is the core problem of personalized cancer medicine…. At the same time, the task is fascinating due to the challenges it poses [for] computational analysis," wrote Dr. Elisabeth Georgii, a postdoctoral researcher at Helsinki Institute for Information Technology HIIT, Aalto University, in an e-mail message. Dr. Georgii is representing TeamFIN, the best-performing team in sub-challenge 1.

The best-performing team in sub-challenge 2 hails from the University of Texas Southwestern (UTSW) Medical Center. Dr. Yang Xie, an assistant professor in the Department of Clinical Sciences at UTSW, is representing her team at the meeting. (A complete list of members from the best-performing DREAM challenge teams is available online.)

The More the Merrier

In addition to a speaking invitation and travel expenses to the DREAM7 Conference in San Francisco for a team representative, the best-performing teams will publish a peer-reviewed Nature Biotechnology paper on the sub-challenge in which their method was the best performer.

If more people participate, it's more likely that we will find a method that will really hit the nail on the head.

—Dr. Gustavo Stolovitzky

"Incentives can go a long way to gather more people who try to solve the challenge. And if more people participate, it's more likely that we will find a method that will really hit the nail on the head," Dr. Stolovitzky noted.

The long-term goal of NCI-DREAM is to apply what was learned from the challenge to improve treatments for cancer patients. "This is the start of being able to make predictions of how to treat a patient based on his or her molecular profile," Dr. Gallahan explained. With that goal in mind, NCI plans to support the subsequent experimental validation and development of the top performing models in the challenge.

"Cancer is such a complex disease that we want to engage as many people in cancer research as possible" he continued. "And if crowdsourcing is one way that we can do that, then that's another tool in our arsenal."

Elia Ben-Ari

Collaborating to Improve Predictions of Breast Cancer Prognosis

The DREAM7 Conference also featured the Sage Bionetworks-DREAM Breast Cancer Prognosis Challenge. The goal of this ongoing challenge is to assess the accuracy of computational models designed to predict breast cancer survival, based on clinical information about the patient's tumor as well as genome-wide molecular profiling data.

The challenge, run by Seattle-based Sage Bionetworks in collaboration with the DREAM Project, is an open computational challenge whose initial, model-building phase used genomic and clinical data from 2,000 women diagnosed with breast cancer. The challenge drew 354 participants—teams and individuals—from more than 35 countries.

Sage Bionetworks is supported in part by the Integrative Cancer Biology Program in NCI's Division of Cancer Biology.

“The Breast Cancer Challenge is an opportunity to leverage the crowd…and demonstrate what happens when you ask researchers to work together rather than on their own,” said Dr. Thea Norman, director of strategic development for Sage Bionetworks. Ultimately, she noted, Sage Bionetworks hopes to organize challenges that improve patients’ lives.

In the final phase of the challenge (expected to end by early 2013), the model that most accurately predicts survival when tested against a novel validation dataset of molecular and clinical data from approximately 250 breast cancer patients will be declared the winner.

Representatives of the two best-performing teams during the model-building phase—Columbia University’s Attractor Metagenes and the University of Pittsburgh’s PittTransMed—were awarded travel expenses and will speak at the DREAM7 Conference. The overall winner or winners of the challenge will publish their results in Science Translational Medicine.

FDA Update

New Treatment Approved for Chronic Myelogenous Leukemia

The Food and Drug Administration has approved omacetaxine mepesuccinate (Synribo) to treat adults with chronic myelogenous leukemia (CML) whose cancer has progressed after treatment with at least two tyrosine kinase inhibitors (TKIs).

Omacetaxine mepesuccinate interferes with the ability of cancer cells to make proteins. The drug is injected just under the skin twice daily for 14 consecutive days over a 28-day cycle until white blood cell counts return to normal. It is then administered twice daily for 7 consecutive days over a 28-day cycle as long as patients continue to benefit.

The drug’s effectiveness was evaluated using a combined cohort of patients whose cancer progressed after previous treatment with two or more TKIs. All of the patients were treated with omacetaxine mepesuccinate.

In 14 of 76 patients with chronic phase CML (18.4 percent), the percentage of cells expressing the Philadelphia chromosome genetic mutation fell within 3.5 months, on average. The median duration of the reduction was 12.5 months.

In 5 of 35 patients with accelerated phase CML (14.3 percent), white blood cell counts normalized or the patient had no evidence of leukemia, within 2.3 months, on average. The median duration of the response in these patients was 4.7 months.

The most common side effects reported during the clinical studies included a low level of platelets in the blood; a low red blood cell count; a decrease in neutrophils, which may lead to infection, fever, diarrhea, nausea, weakness, and fatigue; a reaction at the injection site; and a drop in lymphocytes in the blood.

Omacetaxine mepesuccinate was approved under the FDA’s accelerated approval program, which provides patients access to promising new drugs while the company conducts additional clinical studies to confirm the drug’s clinical benefit and safe use. The drug also received orphan-product designation by the FDA because it is intended to treat a rare disease or condition.

CDC Update

Global Study Documents Tobacco Use, Secondhand Smoke Exposure among Women of Childbearing Age

In low- and middle-income countries around the world, the prevalence of smoking and other forms of tobacco use among women of reproductive age varies greatly, but heavy exposure to secondhand smoke is common, according to a new study by researchers from the Centers for Disease Control and Prevention (CDC) and the World Health Organization. 

The findings were published November 2 in Morbidity and Mortality Weekly Report.

The researchers, led by Van Tong of the CDC, looked at data from the 2008–2010 Global Adult Tobacco Survey on women aged 15 to 49 in 14 different countries. Overall, the analysis showed that 92 million women were current users of tobacco products; smokeless tobacco use was rare, except in Bangladesh and India.

Smoking rates among women in this age group were extremely low in some countries (less than 1 percent in Egypt and Bangladesh) but high in others (about 30 percent in Russia and Poland). Exposure to secondhand smoke was common; about half the women of reproductive age in these 14 countries—nearly 470 million women—were exposed to secondhand smoke in their homes. This exposure varied widely, however, ranging from about 18 percent in Mexico and 26 percent in Ukraine to more than 60 percent in China, Egypt, Turkey, and Vietnam.

"An estimated 62 million births occur annually in these 14 study countries, highlighting the need to protect reproductive-aged women from the harms of tobacco and to promote their health and the well-being of their children," the researchers wrote.

The World Health Organization Framework Convention on Tobacco Control requires countries participating in the treaty to implement evidence-based strategies to reduce tobacco use, including raising prices and taxes on tobacco products, protecting people from exposure to secondhand smoke, enforcing bans on advertising and promoting tobacco products, and providing cessation assistance. These strategies, the authors noted, can prevent or reduce tobacco use and secondhand smoke exposure among reproductive-aged women.

Cancer.gov Update

Newly Launched NCI Map Stories Show Geographic Patterns of Cancer

Screenshot of NCI Map Story: Breast Cancer

NCI's Geographic Information Systems (GIS) & Science website now features a series of interactive maps called NCI Map Stories. The series uses web-based mapping technologies to create narratives about geographic patterns of cancer.

The first Map Story, released in October during Breast Cancer Awareness Month, includes maps showing the most recent breast cancer incidence and mortality rates in the United States. Users can zoom in on the maps to compare incidence and mortality by state and download the data in tables or in PDF format.

Lung, cervical, and colorectal cancer maps are planned for the coming months, and new Map Stories will be released to coincide with national cancer awareness months.

Notes

National Cancer Advisory Board to Meet Later this Month

The National Cancer Advisory Board (NCAB) will meet November 28–30 on the NIH main campus in Bethesda, MD.

The agenda will be available on the NCAB website soon, and the proceedings will be broadcast live online. An archived videocast will be available a few days after the meeting, which will be held in Building 31.

Videocasts of past meetings are available here.

NCI Workshop Will Address Scientific Priorities for Cancer Epidemiology

Trends in 21st Century Epidemiology workshop banner

NCI will hold a workshop December 12 and 13 to help develop scientific priorities for cancer epidemiology research in the next decade. NCI's Epidemiology and Genomics Research Program (EGRP) recently launched a strategic planning effort and is soliciting input on the major questions facing cancer epidemiology research.

Workshop panelists will include prominent cancer researchers, as well as leaders from other NIH institutes and centers. NCI leaders Drs. Robert Croyle, Barry Kramer, Debbie Winn, Stephen Chanock, Robert Hoover, and Patricia Hartge plan to attend. Dr. Michael Lauer, a division director at the National Heart Lung and Blood Institute, will also participate.

The workshop, "Trends in 21st Century Epidemiology: From Scientific Discoveries to Population Health Impact," will be held in Bethesda, MD. Those who cannot attend in person can view a videocast of the workshop and join a LinkedIn and Twitter chat. In preparation for the workshop, EGRP has blogged about topics related to the workshop sessions. Comments from researchers and other interested individuals are welcome.

CancerCare, NCI Seek Submissions for eHealth Video Challenge

Cancer patients, survivors, and their families and friends are invited to submit videos to the eHealth Video Challenge about how they are using information technology to better manage their cancer care, including their treatments and support. The Department of Health and Human Services' Office of the National Coordinator for Health Information Technology established the challenge to encourage the use of consumer e-health tools and other health information technologies.

Some examples of ways that patients are using health IT to be more engaged include

  • Using the web to learn more about a diagnosis and relevant treatment options;
  • Participating in an online community to connect with other patients and caregivers for support;
  • Tracking and managing care and side effects using a personal health record to track and manage care received and side effects; and
  • Using other electronic tools to determine the best treatment plans or to help manage medications, diet, or other activities to enhance cancer treatment, transitional care, and quality of life.

By participating in this challenge, people with cancer have an opportunity to inspire and motivate others with their stories. The project has the potential to improve patients' communication and collaboration with members of their health care teams and to help them better manage their cancer-related care.  

The deadline for submissions is December 12. Find more information about the challenge online, and read a blog about online cancer resources.

Cancer Research Network Scholars Program Accepting Applications

The Cancer Research Network (CRN) Scholars Program is accepting applications for the next round of training, which will begin in March 2013.

CRN is a consortium of nine nonprofit research centers based in health care delivery organizations that supports research at the population level. The CRN Scholars Program consists of 26 months of training that aims to help junior investigators develop research independence. Trainees will use CRN resources to conduct population-based, multisite, and multidisciplinary studies.

The program is open to junior investigators from academic institutions, cancer centers, and other research centers. Applications are due December 15.

The CRN fosters scientific and resource development in areas such as prevention and screening, epidemiology of cancer, prognosis and outcomes, health care quality and cost, communications and dissemination/implementation, and informatics. (More information can be found here.)

To learn more about the program and for application materials, visit the website or contact Program Coordinator Sarah McDonald or Program Co-Directors Drs. Diana Buist or Terry Field.

Quit Smoking with Mobile Resources from NCI

smartphone displaying NCI QuitPal app

NCI has added a new app to its collection of tools and resources to help people quit smoking. NCI QuitPal, a free app for iPhone or iPad, puts proven quit strategies and tools at smokers' fingertips, whenever they need them.

The app contains more than 10 interactive features that allow users to set a quit date and financial goals and to receive reminders. NCI QuitPal also 

  • Tracks daily smoking habits with an easy-to-use calendar;
  • Includes motivational reminders that coincide with progress;
  • Sends health milestones and craving tips;
  • Allows users to connect with social networks and view personalized video messages from loved ones; and
  • Makes it easy to access NCI's free Cancer Information Service by phone or live chat.

To download the app, search "NCI QuitPal" at the App Store or visit the Smokefree.gov website.

NCI has a number of other mobile resources to help people quit smoking, including SmokefreeTXT, SmokefreeTXT en Español, QuitSTART for teens, and the Quit Guide app.

NCI recently released the Quit Guide app for Android. Users who download the Quit Guide from Amazon, Google Play, or iTunes will get insight into what to expect and how to deal with problems that come up during the journey to becoming smokefree.