Canadian researchers have identified a gene mutation that appears to be common in a rare form of ovarian cancer known as granulosa-cell tumors. They discovered the mutation by sequencing RNA from the tumors of four women with the disease, which accounts for up to 5 percent of ovarian cancers. Read more > >
By Dr. Bradford Wood
The new Center for Interventional Oncology was established earlier this year at the NIH Clinical Center (CC) to develop and translate image-guided technologies for localized cancer treatments. The Center is a collaboration involving the CC, NCI, and the National Heart, Lung, and Blood Institute. The Center will draw on the strengths of each institute to investigate how imaging technology and advanced devices can diagnose and treat localized cancers in ways that are precisely targeted and minimally or non-invasive. It will also help bridge the gap between diagnosis and therapy, and between emerging technology and procedural medicine. Read more > >
- NCI Lecture Series Features Dr. Dennis Slamon
- Free Telephone Workshop Series for Cancer Survivors
- Russian Tobacco Control Forum Draws International Participation
- Lance Armstrong Foundation Improves Its Spanish Web Site
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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Genetic Clue to Rare Ovarian Cancers Found
Canadian researchers have identified a gene mutation that appears to be common in a rare form of ovarian cancer known as granulosa-cell tumors. They discovered the mutation by sequencing RNA from the tumors of four women with the disease, which accounts for up to 5 percent of ovarian cancers.
Reporting their findings online in the New England Journal of Medicine last week, the researchers said that the mutation, which changes a single "letter" of DNA, appears to drive the most common form of the disease, the adult type.
They offered two lines of evidence. First, the mutation occurs in a gene (FOXL2) that is essential for the normal development of the cells where the tumors originate. And second, the mutation was found in nearly every granulosa-cell tumor the researchers tested.
"This study shows that virtually all adult type granulosa-cell tumors have exactly the same point mutation," said lead investigator Dr. David Huntsman of the British Columbia Cancer Agency. This knowledge, he added, could be used both to improve diagnostic tools and to develop targeted treatments that counter the effects of the mutation.
Beyond surgery, there are no standard treatments for the disease. In addition, these tumors are often misdiagnosed because they are relatively rare and can appear similar to other cancers. A molecular test based on FOXL2 could potentially improve the accuracy of current diagnostic methods and benefit patients, the researchers said.
Dr. Huntsman and his colleagues initially found the mutation by sequencing all of the messenger RNA—a chemical cousin of DNA—in the four tumors. The researchers went on to show that the mutation was present in 86 of 89 granulosa-cell tumors but not in more than 300 ovarian epithelial and breast tumors.
The mutation came as a surprise, as often happens when genomes are surveyed in an unbiased manner. The researchers were not expecting to find that a single letter of DNA from among the 3 billion in the human genome would be consistently changed in these tumors—or that the change would occur in a gene with a biological connection to the disease.
By focusing on RNA rather than DNA, the researchers uncovered a potentially important mutation for a fraction of the cost of conducting whole-genome sequencing on the same samples, noted an accompanying editorial that praised the study.
While sequencing RNA is less expensive than whole-genome sequencing, the approach also yields less information. In this case, the strategy worked because granulosa-cell tumors are relatively homogenous and have stable chromosomes. This is what made a genome-wide analysis of RNA feasible, the researchers said.
Most cancer genomes, by contrast, have such a range of genetic alterations that investigators may need to sequence hundreds of tumors in order to learn which changes are the most important for a given type of cancer.
The discovery of the FOXL2 mutation represents one of the first clinically relevant discoveries to emerge from the use of the powerful new technologies for sequencing cancer genomes, said Dr. Huntsman. But it will certainly not be the last, he continued, and it will probably not be the most important.
"This is just one example of how laying bare the wiring of cancer cells through sequencing will completely change the way we think about cancer and other diseases," he added.
—Edward R. Winstead
Cancer Research Highlights
Treatment Regimen Extends Survival for Women with Cervical Cancer
Making the chemotherapy drug gemcitabine part of the initial treatment of locally advanced cervical cancer and also part of therapy following primary treatment significantly improved survival for women with locally advanced cervical cancer, according to the results of an international, phase III clinical trial.
Presented recently at the 2009 American Society of Clinical Oncology (ASCO) Annual Meeting, the results have important implications for the treatment of women with cervical cancer in developing countries, where 70 to 80 percent of women are diagnosed at a locally advanced stage due to a lack of widespread screening programs, said lead investigator Dr. Alfonso Dueñas-González of the National Cancer Institute of Mexico.
More than 500 women with stage IIB to stage IVA cervical cancer—from countries as disparate as Pakistan and Panama—participated in the trial. They were randomly assigned to the experimental treatment arm, which included cisplatin and gemcitabine with concurrent external-beam radiation therapy, followed by brachytherapy and adjuvant chemotherapy with gemcitabine and cisplatin. Women in the standard treatment group received cisplatin and concurrent external-beam radiation therapy followed only by brachytherapy.
Approximately 75 percent of women who received the experimental treatment did not experience progression of their disease 3 years after treatment, compared with 65 percent of women who received standard treatment. Overall survival was improved by more than 40 percent, the researchers reported. The research team had expected more toxicity with the addition of gemcitabine, and that is what they saw.
"Overall, the frequency of grade III and IV toxicities was higher in the experimental arm, mainly hematological toxicity," Dr. Dueñas-González said. Grade IV toxicities were low overall, he added, and generally toxicities in the experimental arm were "tolerable and manageable."
The trial "in all likelihood defines a new standard of care" for patients with locally advanced cervical cancer, said Dr. Eric Winer, chief of the Division of Women's Cancers at Dana-Farber Cancer Institute.
Standard Treatment for Anal Cancer Confirmed
The largest clinical study of patients with anal cancer has found that the current standard treatment should not be changed. In addition, patients in the study did not benefit from maintenance chemotherapy that was designed to prevent a recurrence, according to the ACT II study, a phase III, randomized trial involving 940 patients.
Most of the 5,000 patients diagnosed with anal cancer in the United States each year have the squamous cell type, which often responds to radiation therapy and chemotherapy. For a decade, the treatment for anal cancer has been radiation plus 5-fluorouracil (5-FU) and mitomycin-C chemotherapy. In this trial, British researchers asked whether replacing mitomycin-C with cisplatin could improve results for patients, but the answer was no. Furthermore, patients did not benefit from maintenance chemotherapy with cisplatin and 5-FU.
Overall, however, the patients had very good results relative to the international trials published to date, noted Dr. Roger James of the Maidstone Hospital in Kent, who presented the findings at the recent ASCO annual meeting. At 6 months, 95 percent of patients in both groups had all signs of cancer disappear, and at 3 years, nearly 85 percent of the patients in the trial were alive.
Cisplatin was evaluated because it is commonly used to treat other squamous cell cancers, the researchers said, noting that it is not as convenient to deliver and has different toxicities than mitomycin-C chemotherapy. Future trials will likely ask whether certain patients might benefit from other forms of maintenance therapy.
Donated Stem Cell Transplants Better than Self-transplants for Most Patients with AML
Evidence from a meta-analysis of prospective clinical trials supports the use of donated (or allograft) stem cell transplants (SCT) to treat individuals with acute myeloid leukemia (AML). The findings appeared June 10 in the Journal of the American Medical Association.
AML patients are usually classified as good-, intermediate-, or poor-risk, depending on genetic factors linked to the disease. Those in the good-risk group have the best chance of disease recovery and the lowest risk of relapse. The National Comprehensive Cancer Network states that those in the good-risk group should receive SCT from their own body after their initial chemotherapy, or a second round of chemotherapy if SCT is not possible; those in the poor-risk group should have an allograft SCT after chemotherapy; and those who have intermediate-risk disease can be treated either way, because it is not clear if one is better than the other.
Now, an international team of researchers led by Dr. John Koreth at the Dana-Farber/Harvard Cancer Center has reviewed the literature comparing allograft and non-allograft SCT, to determine what the evidence supports for patients in each risk group based on the rates of relapse-free survival and overall survival. The researchers reviewed 24 prospective clinical trials in the United States, Europe, and Japan that included 6,007 adult patients.
Patients who were in the good-risk groups showed no significant difference in relapse-free survival or overall survival if they received a SCT from their own body or from a donor. Those in the intermediate-risk and poor-risk groups, however, showed a clear benefit when receiving allograft SCT compared with SCT from their own bodies.
Overall, the researchers stated, the benefits of allograft SCT were markedly clearer for those in the intermediate- and poor-risk groups. But they noted that "there remains a need to further individualize the allogeneic SCT decision, based on factors like patient age, comorbidity, and the presence of additional molecular lesions."
Restoring MicroRNA Expression Stops the Spread of Liver Cancer in Mice
Researchers from the Johns Hopkins University School of Medicine have shown that restoring the expression of a single microRNA (miRNA) that had been lost in liver cancer cells could prevent tumor growth in mice. miRNAs are short strands of RNA that regulate the activity of genes, including some that are involved in cancer. The study results appeared June 12 in Cell.
The researchers chose the microRNA miR-26a, which is abundant in normal adult liver tissue but lacking in both human liver cancer (hepatocellular carcinoma or HCC) and in the mouse model of HCC used in their experiments.
After initiating liver tumor formation in their mouse model, the researchers restored miR-26a to the tumor cells by injecting a virus engineered to specifically target liver tissue. The virus contained the miR-26a gene and a gene for a fluorescent protein to allow the researchers to visualize successful transfer.
Eight out of 10 mice that received the virus containing the miR-26 gene developed only small tumors or did not develop measurable tumors. The two mice that did develop aggressive tumors had significantly less of the miR-26a gene successfully delivered to their liver tissue. Six out of eight control mice that did not receive the miR-26a gene developed aggressive disease.
miR-26a is not thought to target a specific oncogene responsible for initiating liver tumors. Instead, it worked by generally inhibiting cancer cell proliferation and inducing apoptosis (cell death). No measurable effects were seen in normal liver cells, likely due to their naturally high levels of the miRNA.
The study "provides proof-of-principle that the systemic administration of miRNAs may be a clinically viable anticancer therapeutic strategy," concluded the authors.
Among the Elderly, Adverse Events from Colonoscopy Are Rare
Older individuals who undergo outpatient colonoscopy have a low risk of adverse events, but the risk increases with advancing age and in individuals with certain health conditions, such as diabetes, stroke, and congestive heart failure. The findings are from the first study to assess complications from outpatient colonoscopy in older individuals. NCI researchers analyzed the Medicare records of 53,220 people aged 66 to 95 who underwent colonoscopy between 2001 and 2005.
"Colorectal cancer screening is very important for the prevention of this disease, and we need to know whether colonoscopy is a safe method of colorectal cancer screening as a person gets older and whether there are specific health conditions that can increase one's risk," said lead investigator Dr. Joan Warren of NCI's Division of Cancer Control and Population Sciences. "Until now there have been no data on these questions out there."
As the researchers reported today in the Annals of Internal Medicine, the risk of a serious gastrointestinal event within 30 days following colonoscopy was 6.9 per 1,000 procedures. However, the risk of a serious gastrointestinal event for persons aged 85 and older was more than twice that for persons aged 66 to 69.
The results are consistent with recommendations made last October by the U.S. Preventive Services Task Force, noted Dr. Warren. The Task Force advised against colorectal cancer screening in adults older than age 85 because the potential benefits were small compared to the risks. The group also recommended against routine screening for individuals aged 76 to 85.
The findings will likely contribute to an ongoing debate about the use of screening colonoscopy among individuals who have a limited life expectancy because of advanced age or existing health conditions. In their report, the researchers urged clinicians to incorporate the results into their discussions with patients about the risks of colonoscopy.
Guest Director's Update
New Center Explores Imaging Technologies for Localized Cancer Treatments
Dr. Bradford Wood
Director, NIH Center for Interventional Oncology
The new Center for Interventional Oncology (CIO) was established earlier this year at the NIH Clinical Center (CC) to develop and translate image-guided technologies for localized cancer treatments. The Center is a collaboration involving the CC, NCI, and the National Heart, Lung, and Blood Institute (NHLBI). The Center will draw on the strengths of each institute to investigate how imaging technologies and advanced devices can diagnose and treat localized cancers in ways that are precisely targeted and minimally or non-invasive. It will also help bridge the gap between diagnosis and therapy, and between emerging technology and procedural medicine.
Advanced imaging methods have ushered in an era of earlier detection of cancers that are frequently localized to a single organ or region. Interventional oncology often provides cancer patients with local or regional treatment options to augment the standard cancer treatment options: systemic chemotherapy, surgery, and radiation.
CIO investigators will leverage the interdisciplinary, translational environment at the CC to investigate and optimize how and when to combine drugs, devices, and multimodal imaging navigation. For example, "activatable" drugs can be injected in a vein or artery, then deployed directly in the tumor with needles or catheters using "medical GPS"—a technique that enables the physician to navigate through the body with real-time visualization using the latest advanced imaging technologies, such as magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), or ultrasound.
Images captured earlier can be reused to guide devices delivering targeted therapy to the location of the disease, making the procedure more cost-effective because it doesn't require the system used to record the first image to be physically present. A prior prostate MRI, for example, can be used to help with guided biopsy or focal ablation by using a "medical GPS"-enabled needle and ultrasound, without tying up an MRI system during the procedure.
In another example, a thin needle or sound waves can be used to ablate tumors and enhance targeted drug delivery. Energy sources include high-intensity focused ultrasound, freezing, microwaves, laser, and radiofrequency.
Researchers will also expand investigations into image-guided drug delivery or image-guided "dose painting," where the image can be used to prescribe a particular drug dose to a specific region, by combining targeted, activatable drugs with localized energy or heat to deploy the drug within specially engineered nanoparticles.
The Center will provide a forum to encourage collaborations among researchers and patient-care experts in medical, surgical, urologic, and radiation oncology and interventional radiology. The CC provides an exceptional environment for this type of collaborative translational research and patient care.
Other major program components will include the development of new image-guided methods for personalized drug investigations (or tracking tissue responses to investigational drugs during drug discovery) and first-in-human investigations involving new drugs, devices, image-guided robotic assistance, molecular probes, and nanoparticles.
Many oncologists are not currently familiar with, nor trained in, image based, localized treatment approaches. At the same time, interventional radiologists may lack formal training in oncology. Therefore, education and cross-training will be another important part of the program.
The CIO's collaborative activities will be guided by a steering committee that comprises two NCI appointees, one appointee from NHLBI, and another from the CC. The panel is led by Dr. David Bluemke, director of the Clinical Center’s Radiology and Imaging Sciences Department.
It's with great excitement that I direct this new program, as it is ideally and uniquely positioned to provide an interdisciplinary environment that combines training, patient care, and translational research to accelerate progress in interventional oncology and molecularly targeted interventions.
Undruggable Cancer Genes May Not Be Invincible
Nearly a third of all cancers have mutations in the gene KRAS, yet there are no drugs to combat these changes. And KRAS is not unusual—other common cancer genes are also considered "undruggable."
But as two new studies report, cancer cells driven by these genes may be vulnerable to another kind of attack. A technology called RNA interference can identify "normal" genes in tumor cells that are required for the survival of these cells, and one of these genes may turn out to be an Achilles' heel.
Two independent groups led by researchers at Harvard Medical School used this strategy to search for potential vulnerabilities in cancer cells with KRAS mutations. Both groups found proteins that were essential for the viability of the cells, including some protein kinases. These are promising targets because they can be inhibited by drugs. Imatinib (Gleevec) is one example.
As reported in the May 29 Cell, the researchers used short bits of RNA to target and silence individual genes in cells. While clinical trials will be needed to learn whether patients benefit from this approach, the findings are supported by smaller studies, including one that revealed potential drug targets for diffuse large B-cell lymphoma.
"What these screens do is give us potential leads for new cancer drugs," said Dr. Stephen Elledge, one of the lead investigators. "There must be whole networks of non-oncogenes out there that tumors depend on," he noted, but the genes are difficult to find because they do not have any mutations or alterations.
His team identified a number of genes related to mitosis, including one called PLK1, that are potential therapeutic targets. In tumor cells, KRAS mutations altered the fidelity of mitosis in a way that made the cells die when these genes were inhibited. Thus, cells with KRAS mutations may be vulnerable to antimitotic drugs that target these genes, the researchers said.
Cancer Cells Are "Rewired"
Their findings support the view that cells with cancer-causing mutations are genetically rewired and, through this process, acquire new dependencies. The pathways for growth and survival, for instance, are extensively rewired in cancer cells, and many non-oncogenes play critical roles in the operation of these pathways.
A gene not linked to cancer, STK33, was the top candidate of the second study, led by Drs. William Hahn and Gary Gilliland. Because the gene is essential for the viability of mutant KRAS-dependent cells, the researchers proposed that inhibiting the STK33 protein could potentially treat a broad spectrum of tumors associated with mutant KRAS genes.
In an accompanying commentary, Dr. Charles Sawyers of Memorial Sloan-Kettering Cancer Center said there were "important and immediate" implications for translating these results into the clinic. Identifying inhibitors of STK33 and PLK1 should be relatively straightforward, and clinical trials of such inhibitors could, in principle, begin in 1 to 2 years, noted Dr. Sawyers, who has led the development of targeted cancer drugs.
For now, the importance of these studies is to show that "RNA-interference technology offers a way to develop inhibitors of oncogenes that have until now been undruggable," he wrote in an e-mail. "KRAS mutations are very common, so finding an inhibitor has been a longtime goal of the field."
The Technology Has Arrived
In 1997, researchers at Fred Hutchinson Cancer Research Center predicted that cancer cells had genetic dependencies that could be exploited in drug development, but the tools for discovering these relationships have become available only recently. The reports by Drs. Elledge, Hahn, and Gilliland are among the first to show how researchers can observe, on a genome-wide scale, what happens when a single gene "goes missing" from a tumor cell.
Whether RNA-interference screens will become more common may depend in part on costs. Dr. Gilliland's group used technologies that are beyond the reach of most academic researchers, but the tools used by the other group are available and affordable, Dr. Sawyers noted.
"We need more people doing these genetic screens," said Dr. Elledge. "Hopefully, we have set the stage for this by giving people the information and tools they need to go out and ask these questions."
Given the complexity of cancer and the tendency of tumors to become resistant to single agents, more targets are certainly needed to treat people with this disease. Genetic screens may be part of the solution.
"The key point is that there are lots of potential vulnerabilities in cancer cells, and the technology has now arrived to discover them," he said.
—Edward R. Winstead
A Closer Look
A Sense of Urgency: Rethinking the Clinical Trial Development Process
Low enrollment of adult cancer patients in clinical trials is an ongoing challenge in cancer research. Only about 3 to 5 percent of adults diagnosed with cancer enroll in a clinical trial. A new analysis of federally funded cancer clinical trials sheds light on a barrier to clinical trial enrollment that has until now been invisible: delays caused by the sheer complexity of getting a trial up and running.
"The development time of a clinical trial can be used as an early indicator of accrual success," said Dr. Steven Cheng at the Knight Cancer Institute of Oregon Health & Science University (OHSU), who presented the study findings May 31 at the 2009 American Society of Clinical Oncology (ASCO) Annual Meeting in Orlando. Dr. Cheng and his coauthors reviewed all cancer treatment trials for adult patients sponsored and developed by NCI's Cancer Therapy Evaluation Program (CTEP) between 2000 and 2007.
Trials that went from concept to study activation between 9 to 12 months were significantly more likely to reach their accrual goals than trials with a longer activation time. Trials with the longest activation time (more than 27 months) were the least likely to achieve their accrual goals. Strikingly, 40 percent of more than 550 trials examined fell short of their accrual goals.
Trials that don't meet their accrual goals may close without answering the scientific questions they were designed to address. Failed trials may delay getting potentially beneficial new cancer treatments to patients.
"Resources spent on clinical trials that do not enroll sufficient patients are misappropriated because the underlying scientific objectives are not met," said Dr. Cheng. "One must also consider the ethical implications of enrolling patients onto trials that have a diminished likelihood of achieving success."
Previous work by principal investigator Dr. David Dilts, formerly of Vanderbilt University and now with OHSU's Knight Cancer Institute, has shown that the activation time for a phase III trial sponsored by an NCI-supported cooperative group can range from 10 months to more than 4 years.
"Opening a clinical trial involves hundreds of steps, dozens of decision points, and frequent 'process loops'—points where a change occurs, sending a study protocol back to a previous step," said Dr. Dilts. "Every aspect of the trial is reviewed multiple times and approved by multiple entities.
"People want to do the best science," he added. "So they tweak the protocol to make it better—but every time they do that, it adds months to the process. Those months significantly decrease the likelihood that the study will accrue patients."
A Question of Complexity
Scientific advances have increased the complexity of cancer clinical trials, said Dr. James Doroshow, director of NCI's Division of Cancer Treatment and Diagnosis. For example, many trials now include imaging studies or studies of genetic biomarkers, which provide valuable information about why a treatment works, doesn't work, or works only in some patients. "The most informative trials are often the ones that incorporate these studies, yet doing so adds to the complexity of trial development," he said.
Improving operational effectiveness was a major focus of NCI's Clinical Trials Working Group. Dr. Doroshow is a co-chair of the Operational Efficiency Working Group (OEWG), a task force that NCI Director Dr. John E. Niederhuber charged with devising strategies to reduce by half the activation time for clinical trials conducted by the cooperative groups and NCI-supported cancer centers.
One of the issues being considered by the OEWG is how to restructure financial incentives so that clinicians are able to make clinical trials a higher priority. At the moment clinical work is considered revenue-generating but clinical trials are not.
NCI's network of clinical trial activities developed over many years to meet the evolving needs of patients and clinical investigators, said Dr. Doroshow. "No one ever said, 'Let's make this a harmonized process.' That's our goal now—to create a clinical trials system that is efficient, streamlined, and coordinated."
NCI's Dr. Jeffrey Abrams, associate director of CTEP, agreed and said, "Dr. Dilts' data have driven consensus around the need for major changes in the clinical trials approval process." He also noted that "another challenge confronting NCI-supported Cooperative Groups in this tight funding environment is that increased efficiency may require significant downsizing in the number of trials conducted, which in turn could negatively impact the overall clinical research effort.
Streamlining the Process
Dr. Dilts, an OEWG member whose background is in operations management research, advocates applying process improvement strategies used by companies such as Toyota Motor Corporation and Southwest Airlines to clinical trial development.
"To improve a system's efficiency you first have to study it," he said. "You keep asking 'why?' until you identify the fundamental problem slowing the system down. How many activities are not adding value? Do you really need to have a pre-meeting meeting, a post-meeting meeting, and a post-meeting phone call? Why not get everyone in a room, decide what you're going to do, and be done in 2 hours?"
Finding ways to speed up decision-making is another strategy. Perhaps there should be firm deadlines for submitting clinical trial protocols as there are for R01s and other grant applications, suggested Dr. Dilts. "What if [NCI] said, 'We will fund your trial provided that you submit the final protocol within 90 days?' People generally perform when they are given a deadline.
In his new job as director of clinical research at the Knight Cancer Institute, Dr. Dilts has the opportunity to put his approach to the test. "My role is to create a model for conducting clinical trials efficiently, safely, and effectively," he said.
The Institute's director, Dr. Brian Druker, says his goal is to reduce within 2 years the activation time for a clinical trial to less than 90 days. "We need to create a sense of urgency," he said. "As a clinician I'm tired of talking to patients about a promising new agent, and 6 months later I still can't offer them a trial of that agent because it isn't open yet. Patients need new therapies today.
"It's absolutely clear there are numerous steps [in the development of a trial] that don't add to either its ethical conduct or its scientific validity," he continued. "If we can eliminate or streamline those activities, we can get trials open more quickly and accelerate progress against cancer."
– Eleanor Mayfield
Cancer Center Profile
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Director: Dr. Leland Hartwell • 1100 Fairview Avenue North, Seattle, WA 98109 • Phone: 206-667-5000 • Web site: http://www.cancerconsortium.org
The Fred Hutchinson/University of Washington Cancer Consortium is a research collaboration comprised of Fred Hutchinson Cancer Research Center, an NCI-designated comprehensive cancer center since 1976; the University of Washington (UW); Seattle Children's; and the Seattle Cancer Care Alliance (SCCA). The Hutchinson Center's designation as an NCI comprehensive cancer center was expanded to include the Consortium in 2003.
While the participating institutions remain independent, the Consortium combines their strengths to accelerate research progress in the fight against cancer. The Consortium brings together over 400 faculty members with research interests in basic, clinical, and public health sciences related to cancer, with $116 million in funding from NCI in 2008.
The four participating institutions in the Consortium have a long history of multi-disciplinary collaborations. Faculty members are organized into 13 research programs that emphasize:
- Public health (biostatistics, cancer prevention, epidemiology)
- Clinical research (clinical transplantation, transplantation biology)
- Fundamental sciences (basic sciences, genome instability, stem/progenitor cell biology)
- Programs that impact all three disciplines (cancer imaging; gastrointestinal cancer etiology, risk, and detection; immunology and vaccine development; prostate cancer; women's cancers)
Fred Hutchinson Cancer Research Center is recognized internationally for bone marrow transplantation, which began in the 1960s with the work of one of the Center's founding members, Dr. E. Donnall Thomas, who pioneered the medical procedure that improved leukemia patients' survival from what was once nearly zero to as high as 90 percent. The Hutchinson Center's Bone Marrow Transplant Program, operated through the Seattle Cancer Care Alliance, is now the largest in the world, and its researchers continue to develop and refine new transplantation treatments and protocols and to train doctors worldwide.
Consortium members based at UW have primary faculty appointments in the University of Washington School of Medicine and the School of Public Health. The School of Medicine, founded in 1946, is a top-ranked scientific research institution and a leader in the training of physicians, and the University of Washington Medical Center is one of only four academic medical centers in the United States with dedicated clinical programs involving high-energy radiation therapy with linear accelerator and neutron therapy using a cyclotron.
Seattle Children's comprehensive cancer program treats more pediatric cancer cases than any other provider in the region. Cancer research activities at Seattle Children's include cooperative group clinical trials through its memberships in the Children's Oncology Group (COG), New Advances in Neuroblastoma Therapy Consortium, and the Therapeutic Advances in Childhood Leukemia Consortium. Seattle Children's has been particularly active in the development of protocols for the treatment of acute myeloid leukemia and solid tumors, including brain tumors.
The SCCA is a nationally designated cancer hospital formed in 1998 by the Hutchinson Center, UW, and Seattle Children's. The intent of the partners was to provide an optimal environment for clinical treatment and research by bringing the leading clinical research physicians and scientists of the three outstanding partner institutions together in a single cancer care delivery system. All medical faculty serving at the SCCA have a primary faculty appointment at either UW or the Hutchinson Center.
In 2007, the Consortium provided medical care to more than 4,400 new patients. Though the majority of patients reside in Western Washington state, others are drawn from nearby and distant states, as well as from outside the United States. The Consortium offers a number of special programs that combine the research strengths at the member institutions with the needs of these patients. A cancer prevention clinic, for example, is available to anyone who is interested in learning about their risk for developing some common types of cancer and how they may be able to mediate this risk.
Other Notable Programs
Fred Hutchinson Cancer Research Center is under contract with NCI to serve Alaska, Idaho, Nevada, Oregon, and Washington through the NCI Cancer Information Service's (CIS) Partnership Program, which brings cancer information to organizations that reach people most in need. It also operates one of three CIS Contact Centers, which provides information about cancer and smoking cessation counseling by telephone, TTY, and instant messaging to residents of the United States, Puerto Rico, the U.S. Virgin Islands, and U.S. territories in the Pacific.
Featured Clinical Trial
Optimizing Postoperative Chemotherapy for Breast Cancer
Name of the Trial
Phase III Randomized Study of Adjuvant Cyclophosphamide and Doxorubicin Versus Single-Agent Paclitaxel in Women with Operable Breast Cancer and 0-3 Positive Axillary Lymph Nodes (CALGB-40101). See the protocol summary.
Dr. Lawrence Shulman, Cancer and Leukemia Group B
Why This Trial Is Important
Women who undergo surgery for early stage breast cancer are often treated with postoperative (adjuvant) chemotherapy if they are deemed to have a high risk for recurrence. High risk may be indicated by the presence of cancer in the axillary lymph nodes near the breast that contained the tumor, a large tumor, an absence of hormone receptors in the tumor cells, or other characteristics. Adjuvant chemotherapy is given in hopes of preventing or delaying recurrence of cancer and its spread to other organs.
Currently, adjuvant chemotherapy with the drugs cyclophosphamide and doxorubicin is considered the standard of care. However, this combination carries with it the risk of serious long-term complications, including greater chances of heart problems and development of acute leukemia as a secondary cancer. Researchers want to know if adjuvant chemotherapy using a different drug, paclitaxel, is as effective as cyclophosphamide and doxorubicin in preventing recurrences, with fewer immediate and long-term side effects.
In this trial, women with early stage breast cancer deemed by their doctors to be at high risk for recurrence will receive adjuvant chemotherapy with either cyclophosphamide and doxorubicin or paclitaxel given four times over an 8-week period.
"Paclitaxel has been used in breast cancer treatment for more than 20 years," said Dr. Shulman,"and it has shown equivalency to combination chemotherapy in other breast cancer settings. It hasn't been tested as a single agent, however, in women with early stage disease.
"In this group of patients, we estimate that 80 to 85 percent will be long-term survivors, so the long-term side effects of treatment are very important considerations," added Dr. Shulman. "Paclitaxel hasn't demonstrated the long-term cardiac or leukemia risks of the doxorubicin/cyclophosphamide combination, and it usually causes fewer short-term side effects as well."
Nevertheless, treatment with paclitaxel is not without risks, Dr. Shulman noted. "One of the common side effects of paclitaxel is peripheral neuropathy, a loss of sensation or painful sensation in the extremities. Usually the neuropathy is mild and doesn't persist long, but it is a concern.
"A companion study will look at the quality of life of the women receiving these breast cancer treatments so that we will better understand their side effects," he said.
NCI Lecture Series Features Dr. Dennis Slamon
NCI's Center for Cancer Research (CCR) continues its Eminent Lecture Series, presentations by nationally recognized scientists who work in cutting-edge research, with a talk by Dr. Dennis Slamon on June 22 at 3:00 p.m. in Lipsett Amphitheater on the NIH campus in Bethesda, MD. The title of Dr. Slamon's talk is "Molecular Diversity of Human Breast Cancer: Clinical and Therapeutic Implications."
Dr. Slamon is director of Clinical/Translational Research at UCLA's Jonsson Comprehensive Cancer Center (JCCC). For more than 12 years, he and his colleagues conducted the laboratory and clinical research that led to the development of the breast cancer drug trastuzumab (Herceptin), which targets a specific genetic alteration found in 20 to 25 percent of breast cancer patients. President Clinton appointed Dr. Slamon to a 2-year term on the three-member President's Cancer Panel in June 2000.
The lecture series is free and open to the public. Details about this and upcoming lectures in the series are available online.
Free Telephone Workshop Series for Cancer Survivors
The third and final telephone workshop in NCI's annual Living With, Through, and Beyond Cancer series will be held June 23 from 1:30 p.m. to 2:30 p.m. EDT. Part III of the series is titled "Survivors Too—Family, Friends, and Loved Ones: Managing the Fatigue of Caregiving."
The three-part series offers cancer survivors, their families, friends, and health care professionals practical information to help them cope with concerns and issues that arise after treatment ends. The program is supported by NCI, CancerCare, the Lance Armstrong Foundation, the Intercultural Cancer Council, Living Beyond Breast Cancer, and the National Coalition for Cancer Survivorship.
The workshop is free; no telephone charges apply. To register, visit the CancerCare Web site at www.cancercare.org/TEW. Parts I and II are archived and available as podcasts on the CancerCare Web site:
- Part I: "Managing the Stress of Survivorship"
- Part II: "The Importance of Nutrition and Physical Activity"
Russian Tobacco Control Forum Draws International Participation
The Second Russian Health or Tobacco Forum was held May 25–26 in Moscow. The meeting was organized by the State Duma of the Russian Federation and supported by the American Russian Cancer Alliance (ARCA) and NCI, among others. It showcased progress made in tobacco control since the Duma ratified the WHO Framework Convention Against Tobacco in 2008 and brought together governmental, academic, and nongovernmental entities to further the national strategy on tobacco control.
U.S. Ambassador to the Russian Federation John Beyrle participated in the opening ceremony, and Congressman Steny Hoyer (D-MD), majority leader of the U.S. House of Representatives, provided a video greeting and message to the Forum. ARCA was represented by its executive director, Sophia Michaelson, and by Dr. Paul Engstrom of the Fox Chase Cancer Center, an ARCA partner. Dr. Joe Harford, director of the Office of International Affairs, represented NCI.
Forum participants heard talks on the U.S. experience in tobacco control, as well as those of France, India, and Poland. Many Russian speakers discussed various aspects of the ongoing anti-tobacco activities in Russia, and awards were given to Russian journalists for their anti-tobacco stories in the press. At the conclusion of the meeting a series of recommendations were endorsed, including a significant increase in the price of cigarettes, an emphasis on smoking cessation, establishment of smoke-free zones in all public places, and additional tobacco control legislation that would decrease the availability of cigarettes, especially to minors.
Lance Armstrong Foundation Improves Its Spanish Web Site
The Lance Armstrong Foundation (LAF) has redesigned its Spanish Web site, http://www.LIVESTRONG.org/espanol, to better meet the needs of Spanish speakers and to empower the Spanish-speaking cancer community.
Users can connect to LIVESTRONG SurvivorCare and get answers to questions about cancer, add the new Spanish widget to their desktops to receive LAF updates, watch or listen to online videos and audio about cancer survivorship, and send an electronic greeting card to encourage people affected by cancer to seek support from the Lance Armstrong Foundation.
The site also includes an online training for "promotores," Spanish speakers who promote health in their own communities. The online training focuses on improving the quality of life of Hispanic and Latino cancer survivors.