National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
September 21, 2010 • Volume 7 / Number 18

NEWS

Photo of a physician listening to a child's heart with a stethoscopeDrug Protects Heart in Children Receiving Common Chemotherapy

The drug dexrazoxane, which can protect heart tissue from the oxidative damage caused by doxorubicin and other anthracycline drugs, significantly reduced the occurrence of long-term heart damage in children undergoing treatment for high-risk acute lymphoblastic leukemia (ALL). Importantly, dexrazoxane did not reduce the effectiveness of anthracycline chemotherapy.                                                      Read more > >

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IN DEPTH

UPDATES

  • Cancer.gov Update

    • New Video Highlights a Daughter’s Experience Coping with Her Mother’s Cancer Article contains video
  • FDA Update

    • FDA Sends Warning Letters to Electronic Cigarette Companies
  • Notes

    • Register for Cancer Control P.L.A.N.E.T. Cyber-seminars on Program Dissemination
    • NIH Invites Comments on Draft Strategic Plan for Obesity Research
    • Registration Open for 2010 NCI SBIR Investor Forum

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.

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Featured Article

Drug Protects Heart in Children Receiving Common Chemotherapy

Photo of a physician listening to a child's heart with a stethoscope Children treated with an anthracycline have more than a threefold increased risk of cardiac death 30 years after treatment compared with their untreated peers.

The drug dexrazoxane, which can protect heart tissue from the oxidative damage caused by doxorubicin and other anthracycline drugs, significantly reduced the occurrence of long-term heart damage in children undergoing treatment for high-risk acute lymphoblastic leukemia (ALL).

Importantly, dexrazoxane did not reduce the effectiveness of anthracycline chemotherapy—children in the study had the same risks of long-term recurrence and development of a second cancer regardless of whether they received the protective drug. The results from the study, which was supported in part by a grant from NCI’s Office of Cancer Survivorship, were published online September 15 in Lancet Oncology.

“Our goal has been to change the paradigm of what defines a successful treatment for childhood cancer,” said the study’s lead investigator, Dr. Steven Lipshultz of the University of Miami Leonard M. Miller School of Medicine. “We need to have a balance between oncologic efficacy on one side, which we want to maximize, and the toxicities and late effects, which we want to minimize.”

More than half of children in the United States who have undergone treatment for any type of cancer received chemotherapy with an anthracycline. “What we’ve learned from the first generation of survivors of childhood cancer is that a statistically significant number of these children have late effects of treatment, and one of the most common late effects is damage to the heart, which is progressive over time,” explained Dr. Lipshultz. Children treated with an anthracycline have more than a threefold increased risk of cardiac death 30 years after treatment compared with their untreated peers.

To test whether dexrazoxane could help minimize late cardiac effects, Dr. Lipshultz and his colleagues with the Dana-Farber Cancer Institute Childhood ALL Consortium, which is directed by Dr. Stephen Sallan, enrolled 205 children with high-risk ALL into a randomized trial between 1996 and 2000. The children, who were recruited from nine hospitals in the United States, Canada, and Puerto Rico, received either 10 doses of high-dose doxorubicin (300 mg per square meter of body surface) alone or doxorubicin preceded by an infusion of dexrazoxane.

After treatment, the researchers followed the children with echocardiographic measurements of the heart’s structure and functioning, which they compared with age-appropriate predicted measurements according to data from 285 healthy children at the same hospitals. The physicians recording the outcomes remained blinded to the patients’ treatment assignment throughout follow-up—as long as 15 years at the time of the study’s publication.

Sixty-six children who received doxorubicin alone and 68 children who received doxorubicin and dexrazoxane had at least one echocardiogram after treatment. After 5 years of follow-up, the children who received doxorubicin alone had a statistically significant deficit in several measures of heart functioning compared with their healthy peers, while no statistically significant differences were observed for the children given dexrazoxane.

When parsed by gender, this protective effect was only observed in girls. However, Chief of NCI’s Pediatric Oncology Branch Dr. Crystal Mackall explained, “this was not a large study and hence was not powered to detect potentially smaller differences in protective effects. Since the damage in boys was not as high to begin with, a protective effect of dexrazoxane could have been missed in this study.” Previous studies have suggested that the female heart may be more vulnerable to anthracycline-related damage.

Since this was a small study in a single disease using only one treatment protocol, said Dr. Lipshultz, the researchers encourage further exploration of the subject in cooperative group trials, which have a built-in capability for long-term monitoring of outcomes.

Longer follow-up of the children in the current study will also be needed to determine whether the prevention of non-symptomatic damage to the heart’s structure will result in the prevention of clinical cardiac dysfunction, said Dr. Malcolm Smith, a pediatric cancer specialist in NCI’s Cancer Therapy Evaluation Program.

For now, Dr. Mackall is encouraged by this study. “We knew dexrazoxane could protect the heart in the short term and have been using it here at NCI for the last 20 years, but until now there hasn’t been a randomized study that showed that it was able to protect the heart in the long term,” she said. “There have also been other concerns in the cancer community about dexrazoxane, such as potentially reduced treatment efficacy or second malignancies, which were not born out in this study,” she continued. “This is another piece of evidence that protecting the heart doesn’t protect the tumor.”

—Sharon Reynolds

For more information on this topic, see: “The Heart: An Unintended Victim of Some Targeted Cancer Therapies” and “Protein Helps Predict Cancer Therapy-induced Heart Damage.”

Cancer Research Highlights

Mutations Linked to Two Uncommon Forms of Ovarian Cancer

Mutations in a gene called ARID1A may play a key role in the development of two types of ovarian cancer, according to studies published online September 8 in the New England Journal of Medicine (NEJM) and September 8 in Science Express.

In the NEJM study, Canadian researchers found ARID1A mutations in 55 (46 percent) of 119 samples of ovarian clear-cell carcinoma, which accounts for about 12 percent of U.S. ovarian cancer cases, as well as in 10 (30 percent) of 33 samples of endometrioid carcinoma, another relatively uncommon type of ovarian cancer. No mutations were found in samples from patients with the most common type of ovarian cancer, serous carcinoma, which accounts for about 70 percent of U.S. ovarian cancers.

In the Science Express study, which was smaller but very similar, researchers from Johns Hopkins Sidney Kimmel Comprehensive Cancer Center reported ARID1A mutations in 57 percent of ovarian clear-cell carcinoma tumor samples.

Both ovarian clear-cell and endometrioid carcinoma are associated with endometriosis, a gynecologic condition in which cells that line the uterus proliferate in other nearby areas, often producing severe pelvic pain and other problems. Neither cancer subtype responds well to available therapies.

“Connecting ARID1A gene mutations to endometriotic lesions accelerates us toward the development of tools to determine which women with endometriosis are at increased risk for ovarian cancer,” said the NEJM study’s senior author, Dr. David Huntsman from the British Columbia Cancer Agency, in a news release.

His research team initially identified seven types of ARID1A mutations in a small (discovery) set of 19 clear-cell and endometrioid carcinoma samples and then confirmed the findings in an additional (validation) set of 211 ovarian cancer samples. When the researchers looked more closely at two patients whose clear-cell carcinoma tumors had ARID1A mutations, they found the mutations in nearby endometriotic lesions but not in lesions farther away from the primary tumor. Taken together, the research team wrote, the evidence suggests that ARID1A mutations “may be pathogenic, rather than random, events” and are “an early event in neoplastic transformation.”

The findings, Dr. Huntsman said, via e-mail, suggest that earlier studies implicating the gene in cancer were correct and that ARID1A “appears to be a tumor-suppressor gene of considerable relevance."

Declines in U.S. Smoking Prevalence Stalled

After a period of marked downturns in smoking prevalence in the United States during the 1990s and the early 2000s, smoking rates have held steady for the past 5 years, CDC researchers report. According to their analysis of data from the 2009 National Health Interview Survey and the 2009 Behavioral Risk Factor Surveillance System, 20.6 percent of U.S. adults age 18 and older were regular smokers in 2009, virtually unchanged from the 20.9 percent who were regular smokers in 2005. The findings appeared in the September 10 Morbidity and Mortality Weekly Report (MMWR).

Consistent with previous surveys, smoking rates were somewhat higher among men than women, and there were still dramatic disparities in smoking according to region of the country, income level, and education. For example, smoking prevalence in 2009 among people age 25 and older who did not finish high school compared with those who obtained a graduate degree were 28.5 percent and 5.6 percent, respectively.

Another report in the July 9 MMWR showed that the declines in youth smoking have slowed, but they have not stalled. From 2003 to 2009, smoking among high school students declined by 11 percent, compared with a 40-percent decline from 1997 to 2003. Nearly one in five U.S. high school students reported smoking, the 2009 survey found.

“The slowing in the decline observed for youth cigarette smoking indicates that cigarette smoking among adults and the associated morbidity and mortality will continue to be important public health issues for the foreseeable future,” wrote Dr. Shanta R. Dube and her colleagues from the CDC’s National Center for Chronic Disease Prevention and Health Promotion in their September report.

Both the Patient Protection and Affordable Care Act and the 2009 Family Smoking Prevention and Tobacco Control Act provide “new opportunities” for reducing tobacco use, the researchers wrote. Under the former, access to evidence-based smoking-cessation services and treatments is expected to expand, and the Tobacco Control Act “gives the [FDA] authority to regulate the manufacturing, marketing, and distribution of tobacco products.”

Men with Low PSA Levels May Not Benefit from Further Prostate Cancer Screening

Also in the Journals: PSA Levels and Prostate Cancer Screening

By studying Swedish men who provided blood samples at age 60 and were followed for 25 years, researchers have found that the concentration of prostate-specific antigen (PSA) in the blood at that age was associated with the risk of developing life-threatening prostate cancer later in life. Although men with a concentration below the median (≤1 ng/mL) might harbor prostate cancer, the cancer was unlikely to be fatal. “These men could be exempted from further screening, which should focus on men with higher concentrations,” Dr. Hans Lilja of Memorial Sloan-Kettering Cancer Center and his colleagues reported online September 15 in the British Medical Journal (BMJ).

A second report, also online in BMJ, analyzed data from six randomized trials, involving more than 380,000 men, to assess the benefits and harms of prostate cancer screening. The analysis did not support the routine use of PSA testing with or without digital rectal exam. “Screening leads to an increase in the diagnosis of early-stage prostate cancer that does not seem to translate into a benefit in overall survival and survival specific to prostate cancer,” concluded Dr. Philipp Dahm of the University of Florida College of Medicine in Gainesville, FL, and his colleagues.

Together with the observational study in Cancer by van Leeuwen and colleagues showing a low risk of prostate cancer mortality among men ages 55 to 74 with a PSA level of 0.0-1.9ng/mL, there is accumulating evidence that it may be possible to identify a group at very low risk for prostate cancer death, experts in NCI’s Division of Cancer Control and Population Sciences said.

Men age 55 to 74 who have a low level of prostate-specific antigen (PSA) in their blood may not benefit from further screening or treatment for prostate cancer, according to a study led by Dr. Pim van Leeuwen of the Erasmus University Medical Center in the Netherlands. The study results were published online September 13 in Cancer.

To better understand the potential benefit-to-harm ratio of PSA screening, the researchers compared prostate cancer incidence and mortality among 42,503 unscreened men in Northern Ireland with the incidence and mortality among 43,987 screened men who participated in the European Randomized Study of Screening for Prostate Cancer (ERSPC), a 2009 study that suggested PSA screening could reduce prostate cancer deaths by 20 percent. (The researchers could not compare PSA levels between the screened and control arms of the ERSPC study because baseline PSA levels were not collected for men in the control group.)

Men in both groups were divided into four baseline PSA categories (0.0 to 1.9 ng/mL; 2.0 to 3.9 ng/mL; 4.0 to 9.9 ng/mL; and 10.0 to 19.9 ng/mL) and were followed for a median of approximately 9 years. Men with PSA levels 20 ng/mL or higher were excluded from the study.

In the unscreened Northern Ireland group, 236 men died from prostate cancer during the follow-up period, compared with 109 men in the ERSPC group. This translated to a 20-percent relative reduction in prostate cancer-specific mortality with screening after adjusting for age and baseline PSA, a finding similar to the one previously reported using ERSPC data alone. However, the reduction was not evenly distributed across the four categories.

“A negligible difference in the cumulative hazard in prostate cancer death was observed for men with PSAs [less than 3.9 ng/mL] at study entry,” stated the authors. The number of men who would need to undergo treatment to prevent one death from prostate cancer ranged from 60 men in the highest baseline category (10.0 to 19.9 ng/mL) to 725 men in the lowest (0.0-1.9 ng/mL).

The study had several limitations, explained the authors, including the lack of randomization between the two groups studied, a large difference in all-cause mortality between the groups that could potentially bias the outcomes, and the fact that men in the two groups may have received different treatments for prostate cancer.

Another limitation was that the reason why men were tested at baseline for PSA was not available in the Northern Ireland data. Available evidence indicates, however, that less than 20 percent of PSA tests in this group were in asymptomatic men, while in the ERSPC study presumably almost all of the baseline PSA readings were in asymptomatic men, explained Dr. Eric J. (Rocky) Feuer, chief of the Statistical Research and Applications Branch in NCI’s Division of Cancer Control and Population Sciences.

“The authors indicate that it remains unknown whether men with a specific age and PSA level in a screening population compare equally to men with the same age and PSA in the selected clinical population,” he said. “It is difficult to know to what extent these potential biases could have influenced the overall results of the study.”

The researchers at Erasmus University Medical Center stressed that longer follow-up is needed before clinical recommendations can be made.

Hospitalization Near Death May Diminish Mental Health of Caregivers and Quality of Life for Cancer Patients

Bereaved caregivers of terminally ill cancer patients who died in hospitals or intensive care units (ICUs) are at increased risk for developing psychiatric problems compared with caregivers of patients who died at home, according to a study published online September 13 in the Journal of Clinical Oncology.

The prospective study of 333 dying cancer patients and their closest caregivers—led by Dr. Alexi A. Wright and colleagues at Dana-Farber Cancer Institute, Harvard Medical School, and Brigham and Women’s Hospital—was designed to determine principally whether the place of death for patients with cancer was associated with the patients’ quality of life at the end of life, and also whether it was linked with increased risk for bereavement-related psychiatric disorders in their caregivers.

The researchers reported that caregivers of patients who died in ICUs had an increased risk of developing post-traumatic stress disorder (PTSD) compared with caregivers of patients who died at home with hospice care: 21.1 percent compared with 4.4 percent. “To our knowledge, this is the first study to show that caregivers of patients who die in ICUs are at a heightened risk for developing PTSD,” they wrote. In addition, caregivers of patients who died in the hospital had higher odds of suffering prolonged grief disorder: 21.6 percent compared with 5.2 percent among caregivers of patients who died with home hospice.

Quality of life for the patients was evaluated through reports from their caregivers within 2 weeks of death. The caregiver reports for patients who died in an ICU or hospital revealed more physical and emotional distress and lower quality of life at the end of life, compared with caregiver reports for patients who died at home with hospice services.

Surprisingly, the researchers found that home death was associated with better quality-of-life outcomes compared with outcomes for those who died in the hospital, regardless of whether the patients received hospice services at home.

“Future research is needed to determine why home deaths result in better [quality of life] for patients, but we expect that it may be due to differences in the focus of care provided,” the researchers wrote. “Hospital—and especially ICU—care often focuses on keeping patients alive at all costs, whereas home deaths may emphasize patients’ [quality of life] and symptom management.”

Home death may also improve caregiver outcomes by providing an opportunity for caregivers to deal with the approaching loss and receive support from their community in a familiar environment, they noted.

Spotlight

Survivorship
This is the sixth article in a series of stories related to cancer survivorship. Look for the symbol on the left in an upcoming issue for the next article in the series.

When Ovarian Cancer Returns Years Later

In 1995, when Susan Lowell Butler was unlucky enough to be diagnosed simultaneously with advanced ovarian and advanced breast cancer at age 52, doctors began to talk about her "tumor burden." Of all the medical jargon she was hearing as a patient, this phrase stood out. "I kept thinking of the 'tumor burden' as a backpack on my back," she recalled. But those doctors were able to rid her body of the tumors, and, in the process, she learned more than she ever wanted to know about being a patient with cancer.

UPDATE: Susan Lowell Butler, who is featured in this article and the accompanying video, died on December 18, 2010, as the NCI Cancer Bulletin reported here.

When she emerged from her treatments alive, Butler used this knowledge to help women with ovarian cancer. She co-founded the Ovarian Cancer National Alliance, an advocacy organization, and has served on many advisory boards for NCI and NIH. When President Obama visited the NIH campus last year, Butler was there as the official greeter.

But, unfortunately, her ovarian cancer came back, as this cancer so often does. During a routine colonoscopy 2 years ago, doctors discovered a tumor wrapped around her colon. "Recurrence is the norm in ovarian cancer," Butler said. "Cures are not the norm."

Her treatment options, however, have changed since her original diagnosis. In 1995 she enrolled in a clinical trial sponsored by NCI that was testing three types of chemotherapy. "The thinking with this very intense trial was that killing the cancer cells by several different ways would give people in the trial their best chance at survival," said Butler.

You must have flash installed and enabled to view the video.


Susan Lowell Butler talks about her experience with breast and ovarian cancer and how science and treatment approaches have changed over the years. (Video produced and edited by Sarah Curry.)

Living Longer

Today, clinical trials are increasingly testing drugs that target specific changes in cancer cells. Butler said that her tumor tissue is being tested to try to find a match with one of these agents. Another change over the last decade has been the introduction of more tools for managing the side effects of treatment, which has improved the quality of life for many patients.

"Since I was first diagnosed, a great many new drugs have become available, and these have allowed a lot of women with the disease to live a lot longer than they did in the 1990s," said Butler. At the same time, medications that can reduce or eliminate nausea and other side effects are available and covered by most insurers, she added.

"Fifteen years after Susan Butler's diagnosis, the progress in ovarian cancer has been astronomical," said Dr. Elise Kohn of NCI's Center for Cancer Research, who co-led the trial that helped Butler in 1995. "The number of investigators in the field has increased dramatically, and there is more funding, which has improved the quality and quantity of life for our patients."

The challenge now, Dr. Kohn continued, is to identify the most promising targeted therapies and learn how to use them. Biological markers are needed to identify patients who are likely to benefit from a particular treatment and patients who should be spared the time and expense of treatments that are unlikely to help them.

"The whole field is very excited about targeted therapies," agreed Dr. Deborah Armstrong, an ovarian cancer researcher at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University. "In all cancers, the biggest advances have been coming from targeted therapies, and, unless there's a whole new family of chemotherapy drugs, I don't think we're going to be able to push the envelope there."

Cancer Genomes

Of course, to develop targeted drugs researchers need to understand the genetic changes in the disease, and this information continues to emerge from the lab. (See the related highlight in this issue.) In the coming months, investigators participating in The Cancer Genome Atlas project expect to publish a genomic analysis of hundreds of ovarian tumors and related health information from the tumor donors.

In the meantime, drugs that target several pathways have shown promise in recent reports from clinical trials. The VEGF pathway, for instance, plays a role in the growth and survival of ovarian cancer. Anti-VEGF drugs, like bevacizumab (Avastin), are being tested alone and in combination with chemotherapy with some encouraging results.

Another approach has been to target pathways involved in repairing damaged DNA. Some ovarian cancers have mutations in the genes BRCA1 and BRCA2, which play a role in repairing DNA. Drugs that target the effects of these changes, called PARP inhibitors, have yielded positive results in clinical trials.

"PARP inhibitors clearly have activity in tumors that harbor inherited mutations in BRCA genes," said Dr. Armstrong. "But these drugs look like they may also work in patients with non-inherited (sporadic) ovarian cancers, so that's really exciting." There is also some excitement around drugs that target folate receptors, she noted.

Earlier Detection

For a disease that is usually diagnosed in the later stages, earlier detection is a priority for researchers. But even though many women have cancer beyond the ovaries at the time of diagnosis, doctors are still able to get the vast majority of these patients into remission, noted Dr. Armstrong.

"We are trying to understand the early changes in the disease that will lead us to early detection," said Dr. Kohn. "We'd like to get to the point where breast cancer is; where we identify the disease through techniques like mammography or MRI."

Why the disease comes back is not well understood. One theory is that cells with the properties of stem cells—so-called cancer stem cells—may resist standard treatments and then eventually give rise to new tumors. This hypothesis is being tested for a number of cancers.

In another new area, researchers have identified changes in how RNA is processed in ovarian cancer cells compared with normal cells. These changes could be associated with outcomes in patients with ovarian cancer, researchers at the University of Texas M. D. Anderson Cancer Center reported recently. "We are continuing to make substantial progress in understanding the regulation of the cell's machinery for processing RNA," noted Dr. Anil Sood, who led the study.

The Path Forward

"This disease is proving to be a very complex cancer," said Butler, who now directs the D.C. Cancer Consortium. "All cancers are complex, but this one is particularly devilish." She argues that, along with more research, getting patients to enroll in clinical trials is critical for progress.

 "If you want to move the research along then you need to increase participation in clinical trials," she said. "Otherwise you won't find out the efficacy of what you're testing and you won't get the medicines. It's that simple."

The argument Butler makes is also personal. "If I hadn't found my way onto that clinical trial 15 years ago," she said, "I wouldn't be here talking to you today."

—Edward R. Winstead

A Closer Look

XMRV Researchers Discuss the State of the Science

XMRV virus particles seen by transmission electron microscopy. (Image courtesy of University of Utah Health Sciences Public Affairs) XMRV virus particles seen by transmission electron microscopy. (Image courtesy of University of Utah Health Sciences Public Affairs.)

More than 200 researchers from around the world met this month to discuss XMRV, a recently discovered retrovirus that has been linked to prostate cancer and chronic fatigue syndrome in some but not all studies. The striking discrepancies in results among researchers—with some groups consistently finding the virus in patient samples and others not—led to discussions about how to gather basic information about the virus and advance the science.
 
Everyone who attended the international workshop, held September 7–8 on the NIH campus, agreed that XMRV can infect humans. The virus (xenotropic murine leukemia virus-related virus) was initially discovered in prostate tumors in 2005 and subsequently reported to be present in some patients with chronic fatigue syndrome.

Although XMRV may well be detectable in some prostate cancer and chronic fatigue syndrome patients, there is currently no evidence that the virus causes disease in people. “We don’t know that XMRV causes any human disease,” said Dr. Robert Silverman of the Cleveland Clinic, who was part of the research team that discovered the virus in prostate tumors.

His colleague, Dr. Eric Klein, also a discoverer of XMRV, discussed the possibility that viruses may play a role in prostate cancer as they do in some other cancers. If XMRV were a cause of prostate cancer, then the virus could be a biological marker for identifying specific types of disease as well as a basis for developing a vaccine against the virus, he said.

“What We Know”

NIH Director Dr. Francis Collins noted in his introductory remarks that the science on XMRV was at “a very important juncture.” He stressed that proving an association between a virus and a disease is not the same as proving causation. Urging participants to approach presentations with a healthy skepticism, he said that the workshop would be a chance to discuss “what we know and what we don’t know.”

The workshop included presentations by researchers who have found the virus in patient samples and others who have not. Talks were often followed by questions about the methods used in the experiments and strategies for developing more consistent results across laboratories.

“The good thing about the meeting was that it got people talking to each other who hadn’t had an opportunity to do so, and these exchanges will help us set up collaborations and sharing of techniques and samples,” said Dr. John Coffin of Tufts University, one of the organizers. “I don’t think anyone changed their minds [about the role of the virus in disease], but it was a big step toward helping to get all these discrepancies resolved. It was also helpful to have interactions between scientists and people outside the scientific community, such as advocates.”

Among the potential explanations for why only some groups have found the virus were the selection of patients for the studies, where the patients lived, and laboratory methods, such as how the samples were collected, handled, and processed.

Possible Contamination

Contamination of patient samples by mouse DNA could also play a role in positive results, some researchers said. Mouse cells contain hundreds of DNA sequences that are similar but not identical to XMRV. Contamination is a particular concern because today’s genetic tools are capable of detecting trace amounts of DNA or RNA from mouse viruses or tissues in patient samples.

To make this point, Dr. Coffin showed a picture of his swimming pool and proposed a thought experiment. He said that if a single drop of mouse blood were added to the pool and allowed to mix well, DNA from virus-related sequences in the mouse cells could be detected in a 1 mL sample of water (20 drops) with the tools commonly used to search for XMRV. “That’s how sensitive the tools are today,” he said.

Dr. Ila Singh of the University of Utah agreed that contamination from mice can occur very easily in the lab and urged researchers to be “ultra careful.” Her group recently reported that XMRV was present in malignant prostate cells and was more commonly found in men with aggressive tumors.

“The discrepancies may come down to the tests, or assays, being used, as well as the storage and processing of samples,” said Dr. Stuart LeGrice of NCI-Frederick, one of the organizers. “With this meeting, the groundwork has been laid for focusing on the role of contamination and whether handling and processing play a role in results.”

Some participants also called for creating reference samples that researchers could use to evaluate how well tools detect XMRV. This could include positive samples from patients as well as appropriate negative controls. As one participant said, the field urgently needs a protocol that would give researchers concordant results—regardless of whether those results are positive or negative.

“I suspect that until we have the technological details sorted out we won’t be able to address the more interesting ideas” about whether the virus is involved in human disease, said Dr. Jonathan Stoye of the National Institute for Medical Research, UK, another member of the organizing committee. 

Conflicting Results

Researchers from the Baylor College of Medicine were among those who presented positive results. Bryan Danielson and his colleagues detected XMRV in 32 of 144 patients (22 percent) with prostate cancer from the southern United States. The virus was present in both normal and prostate tumor tissue, which suggests that infection may precede the onset of cancer, the researchers said. 

But another study failed to detect the virus in nearly 800 cases of prostate cancer. Dr. Karen Sfanos of Johns Hopkins University and her colleagues had used two different methods (PCR and immunohistochemistry) to look for XMRV.

“We don’t see the virus in prostate cancer,” said Dr. Alan Rein of NCI-Frederick, who co-led the study with Dr. Angelo M. DeMarzo of Johns Hopkins. “Once we can detect the virus, then we can think about its effects on humans. But first we have to show that the virus is there.”

Reliable, reproducible assays are absolutely essential for moving the field forward, said Dr. Donald Blair of NCI’s Division of Cancer Biology. “The meeting focused people’s attention on the need to collaborate and get to the bottom of why results differ and to understand the biological implications of these differences.”

Dr. Coffin predicted that standard assays for detecting the virus in patient samples should be available within a year. “I’m optimistic,” he said.

With so many scientists working on XMRV, the field could answer basic questions about the virus within months, said Dr. Collins, the NIH director. “Now is a great time to have this meeting, and people should be questioning the data,” he added. “That’s what we’re taught to do as scientists.”

—Edward R. Winstead

A videocast of the final session of the meeting is available online.

Featured Clinical Trial

Combining Vaccine and Antiandrogen Therapy for Prostate Cancer

Name of the Trial
Vaccine Therapy with PROSTVAC/TRICOM and Flutamide versus Flutamide Alone to Treat Prostate Cancer (NCI-07-C-0107). See the protocol summary.

Principal Investigator
Dr. Ravi A. Madan, NCI Center for Cancer Research   

Why This Trial Is Important
Men with prostate cancer who show signs of progressive disease, such as an increasing level of prostate-specific antigen (PSA) in their blood, after treatment with surgery or radiation therapy may undergo another type of treatment called androgen deprivation. Androgen deprivation involves either physical or chemical castration to block the production of testosterone, a male sex hormone that often drives prostate cancer growth. Despite this treatment, some men may continue to experience an increasing PSA level but show no evidence of metastatic disease on imaging scans. These patients are said to have castration-resistant, nonmetastatic prostate cancer (also called stage D0.5 disease). Currently, there is no standard of care for men with this stage of prostate cancer.

A recent study by NCI researchers indicated that combining a therapeutic prostate cancer vaccine that targets the PSA protein with an antiandrogen drug that blocks the binding of testosterone to the androgen receptors in cancer cells may help delay disease progression in these men. Antiandrogen drugs can supplement androgen deprivation therapy in preventing the remaining testosterone in the body from promoting prostate cancer cell growth.

In this clinical trial, men with castration-resistant, nonmetastatic prostate cancer who are undergoing androgen deprivation therapy will be randomly assigned to undergo antiandrogen treatment with the FDA-approved drug flutamide with or without the addition of a PSA-targeting vaccine called PROSTVAC/PSA-TRICOM. Men in the study will take flutamide pills three times a day and potentially receive the vaccine subcutaneously once a month until disease progression. Doctors will monitor the men for signs that the cancer is progressing.

“We hope to attack prostate cancer both hormonally using the androgen blockade of flutamide and immunologically with the vaccine. We believe the vaccine may be able to ‘wake up’ the immune system and have it attack and destroy prostate cancer cells,” said Dr. Madan. “There is some preclinical evidence that suggests that lowering testosterone and then introducing a vaccine may enhance an immune response.

“The vaccine itself does not cause significant side effects,” Dr. Madan added. “Flutamide has some side effects that patients undergoing testosterone-lowering therapy are familiar with, but the main side effects we see with the vaccine are irritation at the injection site and some men experience a mild fever that usually goes away on its own.”   

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

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

Community Update

Quitting Smoking? Find Support on Facebook

Facebook is more than just a place to reconnect with old friends—it’s also a forum to build virtual communities and seek social support. As social media has become an increasingly important part of people’s daily lives, many organizations are turning to Facebook to connect with the public and engage them in online conversations.

Last year, NCI’s Tobacco Control Research Branch (TCRB) launched the Smokefree Women Web site and a companion Facebook page as part of an outreach strategy designed to appeal to younger women and get them involved in efforts to quit smoking.

The Facebook platform acts as a virtual support system, said TCRB’s Dr. Erik Augustson, who leads the project. It provides a place for women to gather, share, and connect with others trying to quit smoking. And starting today, there will be another reason to visit the Smokefree Women Facebook page: video blogs will be posted to the page, showing women talking about topics related to smoking.

“Our Facebook video campaign is brought to real women by real women,” said Alison Pilsner. She leads the mobile team that interviews women about issues such as how they've been successful in quitting, smoking while pregnant, and helping family members or friends quit smoking. The hope is that these videos will serve as a launching point for discussions on the Smokefree Women Facebook page.

“Research suggests that social support might have a particular benefit for women who are trying to quit smoking,” said Dr. Augustson. “Participating in conversations and building a community is a way that new media tools, like Facebook, can help NCI integrate social support into our interventions and remove barriers associated with typical smoking cessation treatments.”

You must have flash installed and enabled to view the video.


NCI's Tobacco Control Research Branch has a new Facebook video campaign where women on the street talk about quitting smoking. (Video produced and edited by Sarah Curry.)

Obstacles, such as taking time off from work or commuting to attend face-to-face support groups, are removed by internet-based interventions, he explained. “Support is available for you whenever you need it, and that is one of the main driving forces that has led us to be involved in social media and why we’re seeking to increase our involvement with it.” To Dr. Augustson’s knowledge, the Smokefree Women Facebook page is one of the first of its kind in the Federal government that seeks to deliver an intervention in this format.

Engaging younger female smokers in smoking cessation efforts is a priority for TCRB because quitting early in life can reduce the health consequences of smoking for both women and their children. Yet previous research has shown that white women in their 40s and 50s were the typical visitors of Smokefree.gov, which is the age that women start getting serious about their quit attempts, Dr. Augustson said.

The new Smokefree Women Web site and social media outreach strategy are intended to target women in their child-bearing years, with the Facebook videos engaging younger audiences so that they can hopefully quit smoking at a younger age, when the health benefits are most pronounced.

Using Web analytic software, TCRB staff will study how the use of the Facebook page and Smokefree Women Web site changes as a result of the video blogs. Who is participating in the online discussions, and what are they saying? The staff is also interested in how information is spread through other online channels, like Twitter, and whether the videos drive traffic to the Web site. This information will be used to refine the campaign and tools. TCRB staff also plan to share their results at scientific conferences.

—Sarah Curry

Cancer.gov Update

New Video Highlights a Daughter’s Experience Coping with Her Mother’s Cancer

Opening image from 'Deep Water' video

The Caregivers, Family, and Friends page on Cancer.gov now includes a video story by Cindy Lollar, an NCI staff member, about her experience supporting her mother, who is an ovarian cancer survivor. The film is also available in a larger format on NCI’s YouTube channel.

“I was a little girl who didn’t want her mother to suffer or to die,” said Lollar, “but I was also an adult daughter who could be there when her parents needed her, even though we lived thousands of miles apart.”

In the film, she describes how she and her mother have charted the emotional terrain of sorting through medical information that can be complex and frightening. The film also highlights how families can contact NCI’s Cancer Information Service for similar help.

FDA Update

FDA Sends Warning Letters to Electronic Cigarette Companies

On September 9, the FDA issued warning letters to five electronic cigarette distributors for what the agency said were violations of the Federal Food, Drug, and Cosmetic Act (FDCA), including unsubstantiated claims and poor manufacturing practices. The companies have 15 days to respond to the letters, FDA officials said.

Electronic cigarettes, or e-cigarettes, are battery-operated devices that hold liquid-filled cartridges containing nicotine and often different flavorings. The devices heat the liquid in the cartridge, transforming it into a vapor that is inhaled by the user. These products are often made to look like small, cigarette-shaped devices, but may also be made to resembles cigars and pipes or to look like everyday items such as pens and USB memory sticks for people who wish to use the product without others noticing.

In a separate letter to the Electronic Cigarette Association, the FDA said the agency intends to “regulate electronic cigarette and related products in a manner consistent with its mission of protecting the public health.” The letter outlines the regulatory pathway for marketing drug products in compliance with the FDCA.

Read more about the FDA’s actions in an online press release.

Notes

Register for Cancer Control P.L.A.N.E.T. Cyber-seminars on Program Dissemination

Banner for P.L.A.N.E.T. Cyber-seminars

NCI’s Cancer Control P.L.A.N.E.T. will be hosting a cyber-seminar series called “Dialogue on Dissemination” this fall, bringing together researchers, policymakers, and practitioners in the field of cancer control to discuss how evidence-based programs can be delivered effectively to the public health community.

The first in this series, scheduled for September 28 from 2:00 to 3:30 p.m. ET, looks at program dissemination from the perspective of cancer control researchers. Guests include Drs. Matthew Kreuter and Ross Brownson of Washington University in St. Louis and Dr. Deborah Bowen of Boston University.

The session will be moderated by Dr. Russell Glasgow, the new deputy director for dissemination and implementation science in NCI’s Division of Cancer Control and Population Sciences, and it will engage participants in a wide-ranging discussion on the successes and challenges of disseminating cancer control research. 

Register to participate in the cyber-seminar on the Cancer Control P.L.A.N.E.T. Web site. The next seminar in this series is on October 26, with guests discussing program dissemination from the policymaker’s perspective, and, at the third seminar on November 16, guests will discuss the practitioner's perspective.

All of the seminars will be available through the Cancer Control P.L.A.N.E.T. archive, as are past cyber-seminars.

NIH Invites Comments on Draft Strategic Plan for Obesity Research

The NIH Obesity Research Task Force is developing an updated Strategic Plan for NIH Obesity Research to guide a broad spectrum of research toward developing new and more effective approaches to addressing obesity. This plan reflects the rapid progress in obesity research and new scientific opportunities that have emerged in the years since NIH published its first strategic plan for research on this topic.

The new draft strategic plan is available for scientific and public comment until October 14.

Registration Open for 2010 NCI SBIR Investor Forum

NCI’s Small Business Innovation Research (SBIR) Development Center will host the 2010 NCI SBIR Investor Forum on November 9 at the Stanford University Alumni Center in Stanford, CA. The event is designed to connect investors and strategic partners with the top SBIR-funded companies developing breakthrough cancer therapeutics and technologies that are primed for commercialization.

The forum will build upon the success of last year’s inaugural NCI SBIR Investor Forum, which attracted nearly 200 leading investors and pharmaceutical and medical device companies. This year’s event will feature private breakout sessions; opportunities to meet with NCI SBIR Development Center staff to discuss emerging technologies and upcoming funding opportunities; and time to network with leaders in cancer research, investment, life sciences, and biomedical technology industries.

Registration is free, but seating is limited. More information is available online.