National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
February 24, 2009 • Volume 6 / Number 4

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NEWS

Abnormal chromosomes in a plasma cell from a patient with multiple myeloma (Image courtesy of Drs. Bart Barlogie and Jeffrey Sawyer of the University of Arkansas for Medical Sciences' Myeloma Institute for Research and Therapy)

Years Before Myeloma, Blood Shows Changes

The vast majority of patients with multiple myeloma develop signature changes in their blood that can be identified years before symptoms of the cancer appear, new research suggests. Using rare prediagnostic blood samples, the researchers were able to detect this precursor stage in some patients up to a decade before multiple myeloma was diagnosed. The findings provide important clues for understanding how the disease begins and progresses, the study authors said. Read more > >

COMMENTARY

Director's Update: Moving Ahead with the Stimulus Funds

With President Barack Obama's signing of the American Recovery and Reinvestment Act (ARRA) on February 17, 2009, came newfound hope in many circles that our economy can start down the road to recovery. As the President himself has said, it will not be easy. This recovery package is just the first step and, undoubtedly, just one of many interventions.

The economic stimulus package presents a tremendous opportunity for the biomedical research establishment. Under the new law, NIH will receive approximately $10.4 billion for use in fiscal years 2009 and 2010, $8.2 billion of which is specifically tagged for research. Of that $8.2 billion, approximately $1.26 billion will go to NCI. NCI's leadership is working under an accelerated timetable to create a spending plan that meets the stimulus package goals.  Read more > >

IN DEPTH

UPDATES

  • CMS Update

    • CMS Proposes No Medicare Coverage for Virtual Colonoscopy
  • Cancer.gov Update

    • Tainted Peanut Products Pose Special Concerns for Cancer Patients
  • Notes

    • Cancer Community Loses Two Leaders
    • Gail Selected for ASPO Award
    • CCR's Gottesman Elected to AAM Board, Three Others Named AAM Fellows
    • HINTS Identifies Hispanic Information-seeking Trends

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

Years Before Myeloma, Blood Shows Changes

The vast majority of patients with multiple myeloma develop signature changes in their blood that can be identified years before the cancer is diagnosed, according to a new study. The changes associated with this precursor stage, called monoclonal gammopathy of undetermined significance (MGUS), are detectable up to a decade before symptoms of the cancer appear.

Abnormal chromosomes in a plasma cell from a patient with multiple myeloma (Image courtesy of Drs. Bart Barlogie and Jeffrey Sawyer of the University of Arkansas for Medical Sciences' Myeloma Institute for Research and Therapy) Abnormal chromosomes in a plasma cell from a patient with multiple myeloma (Image courtesy of Drs. Bart Barlogie and Jeffrey Sawyer of the University of Arkansas for Medical Sciences' Myeloma Institute for Research and Therapy)

The study, reported online January 29 in Blood, is not likely to affect patients immediately, because only a tiny fraction of people with MGUS develop multiple myeloma. But the findings could help researchers understand the natural history of the disease and eventually discover markers for predicting which people with MGUS will progress to cancer.

“We now have a window of time for studying how multiple myeloma begins and progresses,” said lead investigator Dr. Ola Landgren of NCI. “From a research perspective, that’s a big step forward.”

Multiple myeloma is a cancer that affects plasma cells, which are a type of white blood cell. It has been known for decades that some individuals diagnosed with MGUS go on to develop multiple myeloma.

The field has been divided, however, about whether multiple myeloma is always preceded by MGUS. Until now, there has been no good way to explore the question. After all, most myeloma patients do not have prediagnostic blood samples available for analysis, as there would have been no reason to collect them.

Rare Specimens

Dr. Landgren and his colleagues in NCI’s Division of Cancer Epidemiology and Genetics (DCEG) found such samples in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Since 1992, this NCI-sponsored study has collected serial blood samples from more than 77,000 people, making it an invaluable resource for investigating early markers of cancer.

Nearly 3 million specimens, including prediagnostic samples from individuals with multiple myeloma, are stored at the Prostate, Lung, Colorectal, and Ovarian (PLCO) biorepository in Frederick, MD. Nearly 3 million specimens, including prediagnostic samples from individuals with multiple myeloma, are stored at the Prostate, Lung, Colorectal, and Ovarian (PLCO) biorepository in Frederick, MD.

Among this group, the researchers identified 71 people who developed multiple myeloma during the trial. When the team examined prediagnostic blood samples—in essence, looking back in time—almost every patient showed evidence of MGUS, in some cases as early as 10 years before the diagnosis of multiple myeloma.

“This shows once and for all that there is a premalignant stage that preceded virtually every multiple myeloma,” said senior author Dr. S. Vincent Rajkumar of the Mayo Clinic in Rochester, MN. Comparing MGUS to polyps that may precede colon cancer, he said the “study gives us the impetus to find ways to identify the precursor stage and use the information eventually to help patients.”

Dr. John Shaughnessy, who studies multiple myeloma at the University of Arkansas for Medical Sciences and was not involved in the research, called the findings “very provocative.” He praised the study for its scope and size and said that it may encourage the medical community to further scrutinize these precursor states.

“The ultimate question is whether the findings will eventually lead to more preemptive types of therapies,” Dr. Shaughnessy added. 

More than 1,400 researchers and clinicians interested in multiple myeloma and related diseases are expected to attend the XII International Myeloma Workshop, held February 25 through March 1 in Washington, DC.

Tracking an Entity

In theory, one could essentially wipe out multiple myeloma by “treating” MGUS, but no one has figured out how to do this, said study coauthor Dr. Robert A. Kyle of the Mayo Clinic. There currently are no drugs available, and considering how few people with MGUS progress to multiple myeloma, screening for the condition would lead to unnecessary costs and anxiety for many people who would never develop the disease.

Dr. Kyle first described “an entity” called MGUS about 30 years ago. The condition, which is usually discovered incidentally, affects 3 percent of Americans over age 50. About 1 percent of these individuals progress to multiple myeloma each year. Several reports, including a DCEG study in Ghana, show that people of African descent have higher rates of MGUS than Caucasians.

“I’ve felt that MGUS is a precursor lesion of multiple myeloma, and that all patients with the disease have a preceding MGUS or smoldering myeloma,” said Dr. Kyle, referring to another precursor condition that typically involves no symptoms. “The new findings confirm our suspicions.”

He added: “There has been a remarkable increase in knowledge in a relatively short period of time.”

Instant Confirmation

Another new study, published online last week in Blood, confirms the findings. The retrospective analysis of prediagnostic blood samples from a military population found that at least 27 of 30 multiple myeloma cases identified were preceded by MGUS. As in the PLCO Cancer Screening Trial, the researchers tested stored prediagnostic blood samples that, in this case, had been collected about every 2 years.

“We came up with a very similar answer [as the PLCO study], which gives us reassurance that the findings are valid,” said Dr. Michael Kuehl of NCI’s Center for Cancer Research (CCR), who co-led the study with Dr. Brendan Weiss of the Walter Reed Army Medical Center.

These rare prediagnostic samples, such as those from the military or PLCO study, are the only way to study the frequency of MGUS in multiple myeloma, Dr. Kuehl stressed. “You can take patients who have MGUS and follow them prospectively, but you can’t identify the patients who have ‘de novo’ multiple myeloma, if these people exist,” he said.

The samples at hand will be used to look for markers to predict who will progress to cancer. In addition, Dr. Landgren, who recently joined CCR, Dr. Kuehl, and others are developing a longitudinal study for people with MGUS and smoldering myeloma. The goal is to discover markers of progression and, ultimately, strategies for early intervention.

Similar Story in Leukemia

In the February 12 New England Journal of Medicine, Dr. Landgren and his colleagues describe using PLCO samples to explore a precursor state associated with chronic lymphocytic leukemia (CLL). Although this is the most common leukemia among adults in Western countries, the causes and natural history of the disease are largely a mystery.

The researchers identified 45 patients with CLL in the PLCO trial, and all but one had a preexisting condition called monoclonal B-cell lymphocytosis (MBL). Evidence of MBL, which has been reported in family members of CLL patients and others, was present up to 6.4 years prior to a diagnosis of CLL.

“The startling result was that the changes were present in virtually all the CLL cases in the study with prediagnostic blood samples,” said senior author Dr. Neil Caporaso of DCEG. “In a disease with so many unknowns, our findings will have a dramatic effect on the research agenda by giving investigators new leads,” he predicted.

MBL may be present in about 5 percent of Caucasians over age 50. Of this group, 1 percent will progress to CLL that requires therapy. Many researchers have wanted to assess the frequency of MBL prior to a diagnosis of CLL, and a recent technical advance, along with the PLCO samples, finally made the study feasible.

“The PLCO study is an incredible resource,” said Dr. Caporaso. “This blood is a window on the past.” 

—Edward R. Winstead

Cancer Research Highlights

Possible Prostate Cancer Marker Found

Elevated concentration of a compound detected in the tumor tissue, blood, and urine of men with prostate cancer could indicate the aggressiveness of the disease, new research suggests. Levels of the compound, a metabolite called sarcosine, were elevated in men who had localized prostate cancers compared with benign adjacent tissue, and were even higher in metastatic disease. In addition, experiments with cultured cells indicated that sarcosine may actually contribute to the aggressiveness of prostate cancer, making the associated biochemical machinery a possible therapeutic target, the researchers reported in the February 12 Nature.

If confirmed, the discovery could lead to potentially noninvasive tests for identifying aggressive prostate tumors, perhaps by combining a panel of metabolites with other biomarkers. Physicians currently cannot predict which of these tumors are life threatening.

Sarcosine was identified during a systematic analysis of more than 1,100 metabolites in 262 clinical samples, including tissue, urine, and plasma from men without prostate cancer and those who had various stages of the disease. Dr. Christopher Beecher of the University of Michigan Medical School and his colleagues identified 87 metabolites that could distinguish prostate cancer from benign prostate tissue. Six of these, including sarcosine, had even higher levels in metastatic disease.

Additional experiments led by Dr. Arul Chinnaiyan, an NCI Early Detection Research Network investigator at the University of Michigan, implicated sarcosine in prostate cancer progression. Adding sarcosine to benign prostate cells caused the cells to become more invasive, while reducing sarcosine levels in cancer cells reduced their invasive capability and made them behave more like normal cells.

At a press briefing, Dr. Beecher stressed the importance of the unbiased nature of the study, noting that sarcosine had not been associated with prostate cancer previously. Dr. Chinnaiyan added that profiling all of the metabolites in cells, collectively called the metabolome, could complement large-scale investigations of genes and proteins. “This should give us a more holistic picture of the molecular alterations that occur in cancer,” he said.

Fertility Treatments Unlikely to Raise Ovarian Cancer Risk

During the last few decades, women taking fertility drugs in order to become pregnant have not had definitive evidence that such treatments would not increase their ovarian cancer risk. Now researchers from Denmark, who conducted the largest population-based cohort study thus far to address this question, have reported that fertility drugs do not increase a woman’s risk of ovarian cancer. The study, led by Dr. Allan Jensen of the Institute of Cancer Epidemiology in Copenhagen, appeared February 5 in the British Medical Journal.

The study involved 54,362 Danish women who were treated in fertility clinics between 1963 and 1998 and then followed for a median of 15 years; 156 of these women eventually developed invasive epithelial ovarian cancer.

Ovarian cancer risk was no greater for women who used any of four different groups of fertility drugs than for those who had not used these drugs. Of the ovarian cancer cases that did occur in this cohort, 58 percent were serous tumors—occurring in the outer lining of the ovary—and the incidence of this particular tumor type appears significantly higher only among women who had taken clomiphene, which was the most commonly used fertility drug. The authors noted that this association “may be real and important,” but they pointed out that long-term follow-up studies will be needed to confirm this finding. Also, because the usual peak age for ovarian cancer diagnosis is 63 and the average age of these women was only 47 by the end of the study, they will continue to monitor the cohort.

Nevertheless, “Some women who take fertility drugs will inevitably develop ovarian cancer by chance alone,” explained Dr. Penelope Webb in an accompanying editorial, “but current evidence suggests that women who use these drugs do not have an increased risk of developing ovarian cancer.”

Liver Cancer Incidence Continues Steep Climb

A new study by NCI researchers offers both good and bad news about the most common form of liver cancer, hepatocellular carcinoma (HCC). Between 1975 and 2005, the researchers found, HCC age-adjusted incidence rates tripled. However, between 1992 and 2005, HCC survival rates at 1 to 5 years all improved, including a near doubling in 1-year survival. The study was published online February 17 in the Journal of Clinical Oncology.

“Although the study could not determine why liver incidence rates are increasing, these trends may be partially attributable to an increase in chronic infections with hepatitis C virus, which together with hepatitis B virus is a major risk factor for liver cancer,” said the study’s lead author, Dr. Sean Altekruse from NCI’s Division of Cancer Control and Population Sciences.

To conduct the study, the research team analyzed data from NCI’s SEER Program, looking at 10-year birth cohorts from 1900 through the 1950s. Overall, HCC incidence rates increased from 1.6 cases per 100,000 people in 1975 to 4.9 per 100,000 in 2005. Consistent with previous findings, HCC is more often seen in men, for whom the incidence rate was three times higher than women during the study period.

From 1992 to 2005, the most significant increases in HCC incidence rates were in American Indians and Alaska Natives, followed by African Americans, whites, and Hispanics. While overall HCC incidence rates were highest among Asians and Pacific Islanders, these groups had a more modest increase in incidence.

The survival improvements may be due to tumors being diagnosed at earlier stages, but with 1-year overall survival rates still below 50 percent, there is significant room for further improvement, the study authors stressed.

“This report provides reason for optimism that, with more HCC screening of high-risk groups and treatment of low-stage disease, the burden of HCC can be lessened,” they wrote.

Compounds Found in Green Tea Block Bortezomib

Bortezomib (Velcade), a drug approved to treat multiple myeloma and being tested in clinical trials to treat several other cancer types, works by interfering with the activity of proteasomes, cellular structures that break down unneeded proteins. Based on laboratory data, scientists have proposed that compounds found in green tea, including epigallocatechin gallate (EGCG), may increase the effectiveness of bortezomib when given concurrently.

However, in a study published online February 3 in Blood, Dr. Axel Schönthal and colleagues from the University of Southern California found exactly the opposite—EGCG completely blocked the activity of bortezomib in multiple myeloma and glioblastoma cells lines, in tissue cultures from patients with multiple myeloma, and in mice implanted with multiple myeloma cells. In one set of experiments, the EGCG was supplied by a dietary supplement currently available over the counter. A second supplement containing complete green tea extract (GTE), as well as several other individual compounds found in green tea, also interfered with bortezomib-induced cell death.

The researchers found that EGCG directly bound to a chemical group (boronic acid) found in bortezomib. This prevented bortezomib from binding to and blocking the activity of the proteosomes, which would normally cause cell stress and cell death.

“We…would strongly urge patients undergoing [bortezomib] therapy to abstain from consuming green tea products,” stated the authors, “in particular those widely available, highly concentrated GTEs that are sold in liquid or capsule form.”

Gene Provides Target for Thyroid Cancer Treatment

Most targeted anticancer drugs work by decreasing the activity of a mutated gene or reducing the amount of a cell-signaling protein produced by such a gene. Researchers from the Mayo Clinic in Jacksonville, FL, have discovered that an experimental drug currently being tested in a clinical trial to treat anaplastic thyroid cancer (ATC) works in the opposite way, by activating a tumor-suppressor gene called RhoB, which inhibits the production of new cancer cells. Their results appeared online February 10 in Cancer Research.

The researchers tested an experimental drug called RS5444 (also called CS7017) in several thyroid cancer cell lines. They knew from previous work that this drug binds to a protein that can increase the expression of many genes.

Their experiments showed that after treatment with RS5444, this protein binds to and increases expression of RhoB, which then triggers increases in the protein p21, which in turn blocks cancer cell growth. This growth-blocking effect was dependent on RhoB.

Not all ATC cells are susceptible to the class of drugs that includes RS5444. To test whether RhoB could still be a target for therapy in such cells, the researchers treated them with a histone deacetylase inhibitor, which alters the structure of chromosomes and thereby changes the expression of certain genes. They found that altering the genetic structure in this way increased RhoB expression, which in turn increased p21, resulting in suppression of cancer cell growth.

RhoB is implicated as a critical signaling node that could be therapeutically targeted in ATC. Importantly, it is a target that can be up-regulated by multiple classes of drugs,” the authors concluded.

New ASCO/AUA Guideline for Prostate Cancer Prevention

Healthy men who have a prostate-specific antigen score of 3.0 or lower, who have no signs of prostate cancer, and who plan to be screened regularly for the disease should discuss with their physician whether to take 5-alpha reductase inhibitors (5-ARIs) to decrease their risk of developing prostate cancer. This is the recommendation of the American Society of Clinical Oncology (ASCO) and the American Urological Association, published today.

“We are not recommending that all men take 5-ARIs,” said Dr. Barry Kramer, associate director for disease prevention at NIH and co-chair of the panel that developed the guidelines on this topic, in an ASCO press release. “However, we would encourage men to begin a dialogue with their doctors to determine if they could benefit from taking 5-ARIs to reduce their prostate cancer risk.”

The panel’s recommendations are based on the results of clinical trials that have shown men who took this class of drugs, which include finasteride, for between 1 and 7 years had a 25-percent reduced risk of getting prostate cancer. Whether the drugs decrease mortality from the disease, however, is still not clear.

To assist patients with the discussion of 5-ARIs with their physician and their family, ASCO has published a decision aid tool that includes charts and diagrams explaining the risks and benefits of taking these drugs. The tool will be available on ASCO’s patient Web site. The full guidelines will be published in March in the Journal of Clinical Oncology and The Journal of Urology.

Director's Update

Moving Ahead with the Stimulus Funds

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

With President Barack Obama’s signing of the American Recovery and Reinvestment Act (ARRA) on February 17, 2009, came newfound hope in many circles that our economy can start down the road to recovery. As the President himself has said, it will not be easy. This recovery package is just the first step and, undoubtedly, just one of many interventions.

The economic stimulus package presents a tremendous opportunity for the biomedical research establishment. Under the new law, NIH will receive approximately $10.4 billion for use in fiscal years 2009 and 2010, $8.2 billion of which is specifically tagged for research.

Of that $8.2 billion, approximately $1.26 billion will go to NCI. The total funding for cancer research could increase if NCI grantees successfully compete for “challenge grants,” comparative effectiveness research monies, and other infrastructure funds administered by the NIH Office of the Director and the National Center for Research Resources. I believe this sizable figure is a profound affirmation from President Obama and the American people of the importance of tackling the cancer burden and a sign of their confidence that we are well suited to meet that challenge. As you are well aware, I continually remind our leaders in the executive and legislative bodies of our government that an investment in cancer research, whether in basic scientific discovery or behavioral studies of populations, is an investment in a model for gaining an understanding of all diseases.

As I wrote recently, an investment in research does more than just create new scientific knowledge and advances in clinical medicine. That investment also translates into support for research projects at institutions large and small across the country, and those projects in turn create jobs and a plethora of new business opportunities by generating patents, products, and biotechnology start-up companies. In fact, on average, a single NIH research grant supports seven jobs. And according to one analysis, for every $1.00 spent on research in a given community, $2.25 in local economic activity is generated.

The White House is requiring an unprecedented, but certainly appropriate, level of transparency and accountability with regard to how ARRA funds are used. These funds will be kept separate from our general operating budget secured via the standard appropriations process.

To help achieve this transparency, new NCI reporting mechanisms are being developed for the grantees and institutions that receive funds from the stimulus package. These 2-year awards will be supported via three primary mechanisms:

  • Already reviewed, highly meritorious R01 applications that make scientific sense to fund for only 2 years, as well as new R01 applications that have a reasonable expectation of making progress in 2 years
  • Administrative and competitive supplements to current grants
  • Challenge grants, which are intended to provide jumpstart funds for projects that address defined health and science challenges, and where it is believed reasonable
    progress is feasible in a 2-year time frame

NCI’s leadership is working under an accelerated timetable to create a spending plan that meets the stimulus package goals, while striking an all-important balance between increases in the number of grants for individual investigators, where there are long-term financial obligations, and a greater commitment to solicited, team-science projects—such as IT-related efforts like caBIG, BIG Health, and efforts related to the development of electronic medical records.

We will widely report—via the NCI Web site, the NCI Cancer Bulletin, teleconferences, professional meetings, and other avenues—on the research opportunities created by these funds, the specific projects they support, the scientific knowledge and advances they generate, and the number of jobs they provide. NCI is committed to ensuring that the cancer community and general public can easily trace the return on this unprecedented investment.

The bottom line is this: NIH and NCI leadership are prepared to do our part toward the economic recovery of this great country by quickly distributing stimulus funds via a science- and merit-driven process and, in so doing, supporting not just new science but crafting new approaches that alter the course of cancer while preserving and creating jobs.

It’s rewarding to witness members of Congress—particularly Senator Arlen Specter, who championed the need for these funds—and the President’s confidence in the potency of biomedical research in the recovery process. Many in the cancer community toil behind the scenes, in basic research laboratories, community clinics, and the offices of advocacy organizations. But we are all committed to reducing the cancer burden, and this influx of funds recognizes the remarkable work we have done and the important achievements the American people believe we can accomplish.

Indeed, during the signing ceremony last Tuesday, while talking about the support for scientific research in the stimulus package, President Obama said that he hoped “this investment will ignite our imagination once more, spurring new discoveries and breakthroughs.” I am confident that we as a community have the people and strategies in place to live up to that hope, to achieve important progress that will better the lives of millions in the process.

Dr. John E. Niederhuber
Director, National Cancer Institute

Special Report

Newly Discovered Mutation Found in More Brain Tumors

A recent survey of genomic changes in brain tumors found that a gene called IDH1 was mutated in more than 10 percent of the glioblastoma tumors analyzed. The mutations tended to occur in younger patients and were associated with a somewhat longer survival compared with patients who lacked the mutations.

A follow-up study by researchers at the Duke University Medical Center and Johns Hopkins Kimmel Cancer Center now shows that IDH1 and a related gene, IDH2, are frequently altered in three types of gliomas, the most common form of brain cancer. These include low-grade astrocytomas, oligodendrogliomas, and secondary glioblastomas.

The mutations were not detected in nearly 500 other tumors from outside the central nervous system. And among gliomas, IDH mutations often occurred in lower-grade tumors, suggesting that the changes may help initiate and drive these cancers, the researchers reported in the February 19 New England Journal of Medicine (NEJM).

Until last year, IDH1, which is involved in producing energy for a cell, had not been associated with brain cancer. While it is not yet clear how the IDH mutations might affect the genes or cells, an analysis of 445 brain tumors showed that the mutations are localized to certain regions of the genes.

“These are very specific mutations,” said lead investigator Dr. Hai Yan of Duke University. The mutations may affect approximately 6,000 children and adults with brain cancer in the United States each year, the researchers estimate.

The study confirmed the earlier finding that patients whose glioblastomas carried IDH1 mutations had improved outcomes over those whose tumors did not, and it extended the finding to include IDH2 mutations. Patients with a glioblastoma carrying mutations in either gene survived on average 31 months, versus 15 months for those without the mutations.

In addition, patients with anaplastic astrocytomas that tested positive for the mutations had a median survival of 65 months, compared with 20 months for those who did not. (It was not possible to compare survival data for patients with oligodendrogliomas because there were not enough tumors that lacked the mutations.)

The researchers believe, based on these results and studies of the mutations in cultured cells, that gliomas with IDH mutations are a clinically and genetically distinct group of tumors. If this is confirmed, the mutations could be a marker for classifying patients with similar types of disease and prognoses, as well as provide leads for developing therapies targeted at the underlying changes in these tumors.

“As a next step, we need a better understanding of how the mutations might contribute to cancer,” said coauthor Dr. D. Williams Parsons, a visiting professor at Johns Hopkins and an assistant professor at Baylor College of Medicine.

“And from a clinical perspective,” he continued, “it will be important to follow patients with these mutations and see whether they have better or worse outcomes or responses to specific therapies.”

Because IDH genes encode metabolic enzymes, Dr. Yan noted, studying the mutations could lead to new insights into possible connections between metabolism and cancer. This is an area of growing interest among researchers and the subject of an accompanying editorial in NEJM by Dr. Craig Thompson of the University of Pennsylvania School of Medicine.

“A potential benefit of identifying metabolic-enzyme mutations that are pathogenic in specific cancers is that such cancers may be susceptible to pharmacologic manipulations that are more effective and less toxic than existing therapies,” Dr. Thompson concluded.

—Edward R. Winstead

Featured Clinical Trial

Lenalidomide Maintenance Therapy for Multiple Myeloma

Name of the Trial

Phase III Randomized Study of Lenalidomide as Maintenance Therapy after Autologous Stem Cell Transplantation in Patients with Multiple Myeloma (CALGB-100104). See the protocol summary.

Dr. Philip McCarthy Dr. Philip McCarthy

Principal Investigators

Dr. Philip McCarthy and Dr. Kenneth Anderson, Cancer and Leukemia Group B; Dr. Edward Stadtmauer, Eastern Cooperative Oncology Group; Dr. Sergio Giralt, Blood and Marrow Transplant Clinical Trial Network

Why This Trial Is Important

Multiple myeloma is a type of blood cancer that develops in plasma cells. Treatment for multiple myeloma is usually effective in bringing about remission or stopping disease progression, but it rarely provides a cure. Most patients will eventually have a relapse or progression and will die from their disease.

Multiple myeloma treatment usually starts with chemotherapy to reduce the amount of disease. This initial treatment, called induction therapy, is often followed by consolidation therapy, which consists of high-dose chemotherapy, single or tandem autologous or allogeneic stem cell transplantation (SCT), or both. Maintenance therapy is then sometimes given in an attempt to prolong the duration of remission.

The addition of the drug lenalidomide (Revlimid; CC-5013) to induction therapy for multiple myeloma has been found to increase both the rate and the duration of remission compared to earlier regimens. In this trial, researchers are exploring whether maintenance therapy with lenalidomide following autologous SCT can slow or prevent the return of cancer. Patients who have had induction therapy will undergo single autologous SCT and then be randomly assigned to receive either maintenance lenalidomide or placebo.

“An earlier clinical trial has shown that maintenance therapy with thalidomide improves survival after autologous SCT in patients with myeloma,” said Dr. McCarthy. “However, a high number of patients stopped treatment because of toxicity associated with thalidomide.

“Lenalidomide is a derivative of thalidomide that may be more potent and less toxic, so we have good reason to believe that lenalidomide maintenance therapy may help extend the length of remission in patients who respond to autologous SCT and perhaps help those with partial responses to SCT achieve complete response,” Dr. McCarthy said.

“Another exciting aspect of this study is that it demonstrates an important initiative among U.S. researchers to coordinate and collaborate on multiple myeloma clinical trials,” he added. “We believe this cooperative effort will improve the efficiency of multiple myeloma trials and ultimately benefit patients by speeding up the development and validation of new treatments.”

For More Information

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

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

Cancer Center Profile

Dana-Farber/Harvard Cancer Center

Director: Dr. Edward J. Benz, Jr. • 44 Binney Street, Boston, MA  02115
Phone: 617-632-2100 • Web site: http://www.dfhcc.harvard.edu

Background

Founded in 1997, Dana-Farber/Harvard Cancer Center (DF/HCC) is a cancer research consortium that integrates and builds upon the collective talent and resources of seven Harvard University-affiliated institutions. DF/HCC succeeds Dana-Farber Cancer Institute—one of the first Comprehensive Cancer Centers established in the early 1970s—as an NCI-designated comprehensive cancer center. The institutional members of DF/HCC are:

Dana-Farber/Harvard Cancer Center comprises seven institutions throughout the greater Boston area (clockwise from top left): Beth Israel Deaconess Medical Center, Harvard Medical School, Children's Hospital Boston, Dana-Farber Cancer Institute, Harvard School of Public Health, Brigham and Women's Hospital, and Massachusetts General Hospital. Dana-Farber/Harvard Cancer Center comprises seven institutions throughout the greater Boston area (clockwise from top left): Beth Israel Deaconess Medical Center, Harvard Medical School, Children's Hospital Boston, Dana-Farber Cancer Institute, Harvard School of Public Health, Brigham and Women's Hospital, and Massachusetts General Hospital.
  • Beth Israel Deaconess Medical Center
  • Brigham and Women’s Hospital
  • Children’s Hospital Boston
  • Dana-Farber Cancer Institute
  • Harvard Medical School
  • Harvard School of Public Health
  • Massachusetts General Hospital

Member institutions combine their scientific strengths to accelerate research findings from the laboratory, clinical research trials, and studies of populations, enhancing patient care and our understanding of the underlying causes of cancer. DF/HCC members receive a total of $533 million for cancer research funding annually, of which $218 million is from NCI, making DF/HCC the leading recipient of NCI funding in the country.

Research

DF/HCC brings together more than 1,000 faculty members through multidisciplinary, inter-institutional programs that stimulate collaboration and discovery. The Center currently supports 17 established disease- and discipline-based research programs, as well as 10 developing programs. DF/HCC has also been awarded eight Specialized Programs of Research Excellence (SPOREs) in the areas of breast, lung, kidney, ovarian, prostate, renal, gastrointestinal cancers, and myeloma.

Eighteen shared resources or core facilities provide specialized services that enable investigators to conduct innovative cancer research. Of note is the new Pathology Specimen Locator Core, which houses a groundbreaking Web-based network of searchable databases containing de-identified, coded, pathologic information on post-diagnostic, excess human samples that researchers may use in their studies.

DF/HCC also has one of the largest clinical research programs in the country, taking a unified approach to approving, activating, monitoring, and supporting the cancer-related clinical trials conducted at member institutions. Annually, the Center conducts 500 active therapeutic clinical trials, many at multiple DF/HCC sites. Half of these trials are initiated by their principal investigators.

Other Programs

A cornerstone of DF/HCC’s mission is the Initiative to Eliminate Cancer Disparities (IECD), a strategic initiative to address inequalities in cancer across population groups. The IECD focuses on five areas: increasing research on cancer disparities, engaging diverse communities in improving cancer prevention and treatment, increasing the number of minorities in the biomedical workforce through training outreach programs, enhancing faculty diversity, and amplifying culturally sensitive care within DF/HCC member institutions.

CMS Update

CMS Proposes No Medicare Coverage for Virtual Colonoscopy

Under a proposed decision memorandum issued on February 11 by the Centers for Medicare and Medicaid Services (CMS), virtual colonoscopy—also known as CT colonography—for colorectal cancer screening would not be covered by Medicare. In the memo, CMS said the “evidence is inadequate to conclude that CT colonography is an appropriate colorectal cancer screening test” to be covered for Medicare beneficiaries.

The decision by CMS, which is open for public comment until March 11, is in line with recommendations published last October by the U.S. Preventive Services Task Force. It conflicts, however, with the conclusions of the American Cancer Society, from which updated guidelines on colorectal cancer screening were issued that include virtual colonoscopy as an acceptable screening test alongside options like a standard optical colonoscopy and flexible sigmoidoscopy.

The study results published to date, including those from the NCI-funded ACRIN 6664, indicate that for detecting polyps sized 10 mm or larger, virtual colonoscopy and standard optical colonoscopy are equally effective. For polyps 6 mm or less, there is some controversy about the cancer risk they pose, and the agency noted that the data indicate virtual colonoscopy is less reliable than standard colonoscopy for detecting these smaller polyps. There is also some debate about whether virtual colonoscopy misses depressed or “flat” polyps.

Virtual colonoscopy may be considered cost effective at specific reimbursement rates, CMS noted in the decision memo. However, it also states: “A pivotal, overarching concern is the generalizability of these main study results to the Medicare population. The mean age of participants in these studies…was considerably younger than the Medicare aged population.”

Cancer.gov Update

Tainted Peanut Products Pose Special Concerns for Cancer Patients

Peanut Product Recall. Fact Sheet for Cancer Patients.

To assist the FDA with its efforts to inform the public about the recall of peanut products produced by Peanut Corporation of America, NCI has posted a special fact sheet on the Cancer.gov Web site, outlining the particular risks of salmonella-contaminated foods for cancer patients who may have impaired immune systems due to chemotherapy or blood cell transplantation.

This fact sheet also provides suggestions for alternative foods that can provide the higher calories and protein that cancer patients often need during treatment and recovery—various cheeses, beans, yogurt, hummus, and pudding, for example. The fact sheet notes that almond butter and other spreads that are made from nuts are often made with the same equipment that processes peanut butter and, therefore, should be avoided if the source of the product is unclear.

A complete list of products included in the peanut recall is posted on the FDA’s Web site, which includes a search function by which people can enter products according to brand name, UPC code, description, or any combination thereof.

Notes

Cancer Community Loses Two Leaders

Dr. Stephen Williams Dr. Stephen Williams

Dr. Stephen Williams, founding director of Indiana University’s (IU) Melvin and Bren Simon Cancer Center, died of melanoma on February 15. Under his leadership, the Simon Cancer Center experienced tremendous growth, including the opening last year of a $150 million facility at IU’s medical complex in downtown Indianapolis. Dr. Williams authored more than 150 medical articles. His research interests included ovarian and prostate cancer and identifying new treatments for epithelial cancer.

Dr. Williams spoke about his fight against cancer as he received the IU President’s Medal of Excellence in August, when the Simon Cancer Center celebrated its expansion.

“In the last couple of years, I myself have become a cancer survivor and recently completed a very difficult treatment,” he said. “As I reflect on the last few months and how difficult it has been for me, it is absolutely clear that treatment, while important, is not good enough. I can say definitely that it is easier to prevent and detect cancer than it is to treat it.”

Dr. Eugenia Calle Dr. Eugenia Calle

Dr. Eugenia Calle, former vice president of epidemiology at the American Cancer Society (ACS), died suddenly February 17. An Atlanta, GA, man has been charged with her death.

Dr. Calle contributed groundbreaking research on the causes and prevention of cancer. Among her major accomplishments were two landmark studies on the relationship between obesity and cancer, contributions to understanding the risk factors for breast and other cancers in women, and research on hormone-replacement therapy in relation to female cancers. She served as an adjunct professor of epidemiology at the Rollins School of Public Health at Emory University, a member of NCI’s Board of Scientific Counselors, several NCI subcommittees, and on the editorial boards of several cancer journals.

“Jeanne was one of the world’s most respected epidemiologists, researching the causes of cancer, especially obesity and diet,” said ACS President Dr. Otis Brawley in a statement. “Jeanne brought a formidable intellect and passion for finding answers to cancer through her research. We are shocked and deeply saddened by the senseless loss of this tremendously talented friend and colleague.”

Dr. Mitchell Gail Dr. Mitchell Gail

Gail Selected for ASPO Award

Dr. Mitchell Gail, senior investigator with the Biostatistics Branch of NCI’s Division of Cancer Epidemiology and Genetics, has been selected to receive the 2009 Distinguished Achievement Award from the American Society of Preventive Oncology (ASPO). The award will be presented at the Society’s annual meeting, which will be held in Tampa, FL, from March 8–10. ASPO established this award in 1983 to recognize individuals whose research has greatly advanced its mission of cancer prevention and control.


CCR's Gottesman Elected to AAM Board, Three Others Named AAM Fellows

Dr. Susan Gottesman Dr. Susan Gottesman

Dr. Susan Gottesman, a scientist from NCI’s Center for Cancer Research (CCR), was one of six new governors elected to the Board of the American Academy of Microbiology (AAM) earlier this month. Dr. Gottesman, co-chief of the Laboratory of Molecular Biology and head of the Biochemical Genetics Section, studies small regulatory RNAs. She was elected to the National Academy of Sciences in 1998 and the American Academy of Arts and Sciences in 1999 in recognition of her work on energy-dependent proteolysis.

Governors on the Board serve a 3-year term and set strategic direction for the Academy, ratify election to Fellowship, develop new topics for colloquia, and establish new programs and initiatives consistent with its overall mission.

Dr. Giorgio Trinchieri Dr. Giorgio Trinchieri

Three scientists from CCR were among the 72 microbiologists elected AAM Fellows earlier this month.

Dr. Giorgio Trinchieri, director of CCR’s Cancer and Inflammation Program and chief of the Laboratory of Experimental Immunology, focuses on the role of inflammation, innate resistance, and immunity in carcinogenesis, cancer progression, and prevention or destruction. Dr. Trinchieri is credited with discovery of the molecule interleukin-12.

Dr. Jeffrey Strathern Dr. Jeffrey Strathern

Dr. Jeffrey Strathern is chief of the Gene Regulation and Chromosome Biology Laboratory. As head of the Genome Recombination and Regulation Section, Dr. Strathern’s research focuses on mechanisms of genetic recombination, particularly double-strand-break repair, and mechanisms of gene regulation, including gene silencing.

Dr. Amar J.S. Klar Dr. Amar J.S. Klar

Dr. Amar J.S. Klar is a senior investigator in the Gene Regulation and Chromosome Biology Laboratory and head of the Developmental Genetics Section. Dr. Klar’s main research focus is the genetics and molecular biology of gene silencing and mating-type switching in yeast. In other research, his lab has explained the mechanism of asymmetric cell division, which is used to explain brain hemispheric differentiation in humans and visceral organ laterality in vertebrate development.

Fellows of the Academy are elected annually through a selective peer-review process based on their records of scientific achievement and original contributions that have advanced microbiology. Fellows represent all subspecialties of microbiology, including basic and applied research, teaching, public health, industry, and government service.

HINTS Identifies Hispanic Information-seeking Trends

HINTS Brief on cancer information-seeking experiences among Hispanics in the United States

Compared with other racial and ethnic groups, Hispanic populations are significantly less likely to look for information about cancer and less likely to feel confident in their ability to find such information, according to a new analysis of data from NCI’s Health Information National Trends Survey (HINTS). HINTS is a cross-sectional health communication survey of U.S. adults that tracks trends in health information usage over time and cancer-related communication, knowledge, attitudes, and behavior in the population. This recently released HINTS Brief, available in both English and Spanish, indicates that Hispanics, particularly Spanish-speaking Hispanics, experience greater challenges to seeking and interpreting cancer information. Differences in cancer information seeking and information access may contribute to disparities in health outcomes among disadvantaged populations.