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December 13, 2011 • Volume 8 / Number 24

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Late Effects May Not Warrant Using Radiation to Treat Early-Stage Hodgkin Lymphoma

Hodgkin lymphoma cells Patients with early-stage Hodgkin lymphoma who were treated with multidrug chemotherapy alone were more likely to be alive 12 years later than patients who received treatment that included radiation therapy, according to findings from a phase III clinical trial. More patients who received radiation therapy died of second cancers or other toxic late effects of their treatment, such as heart disease, than those who received chemotherapy alone, researchers reported Monday at the American Society of Hematology (ASH) annual scientific meeting in San Diego. The findings, which are the first long-term results from a randomized trial involving patients with early-stage Hodgkin lymphoma, also appeared online December 11 in the New England Journal of Medicine.   Read more > >


Secretary Kathleen Sebelius

mHealth Summit Keynote Address by Secretary Kathleen Sebelius

The Honorable Kathleen Sebelius, secretary of the Department of Health and Human Services, delivered the following remarks at the mHealth Summit on December 5 in Washington DC. 

Dr. Barry Kramer

A Conversation with Dr. Barry Kramer about Cancer Prevention Research at NCI

Dr. Barry Kramer, the new director of NCI's Division of Cancer Prevention, talks about prevention and screening research.


NCI Cancer Bulletin Publication Break

The NCI Cancer Bulletin will not be published on December 27. Our next issue will be published on January 10, when we resume our usual biweekly publication schedule. You'll find some of the important research news and feature stories we covered this year on our 2011 Editors' Picks list.

If you are not yet a subscriber, please enter your e-mail address in the box in the top right-hand corner to begin your free subscription.



  • Notes

    • In Memoriam: Lloyd Old, Cancer Immunology Pioneer
    • Barbara Rimer and Owen Witte to Join the President's Cancer Panel
    • National Cancer Advisory Board Holds Final Meeting of 2011 Article contains video
    • Toby Hecht Appointed Associate Director of Translational Research Program
    • NCI Launches Text Message Service to Help Teens Quit Smoking
    • Radiation Epidemiology and Dosimetry Course Available Online
    • Funding Available to Support Collaborations between U.S. and Chinese Scientists

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

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Featured Article

Late Effects May Not Warrant Using Radiation to Treat Early-Stage Hodgkin Lymphoma

Hodgkin lymphoma cells Hodgkin lymphoma is a cancer of the immune system marked by the presence of large cells called the Reed-Sternberg cell. The number of these cells increases as the disease advances. Photo by Wellcome Images

Patients with early-stage Hodgkin lymphoma who were treated with multidrug chemotherapy alone were more likely to be alive 12 years later than patients who received treatment that included radiation therapy, according to findings from a phase III clinical trial. More patients who received radiation therapy died of second cancers or other toxic late effects of their treatment, such as heart disease, than those who received chemotherapy alone, researchers reported Monday at the American Society of Hematology (ASH) annual scientific meeting in San Diego. The findings, which are the first long-term results from a randomized trial involving patients with early-stage Hodgkin lymphoma, also appeared online December 11 in the New England Journal of Medicine.  

The overall survival rate was 94 percent for patients treated with the drugs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD regimen), compared with 87 percent for patients who received either radiation therapy alone or ABVD plus radiation therapy. Of 405 patients enrolled in the trial, 12 in the ABVD-alone group died during the follow-up period (six of Hodgkin lymphoma, four of second cancers, and two of other causes). In contrast, 24 patients in the group receiving radiation therapy died (4 of Hodgkin lymphoma, 10 of second cancers, and 10 of other causes).

All of the trial's participants had stage IA or IIA Hodgkin lymphoma, with tumors smaller than 4 inches in diameter. Hodgkin lymphoma occurs most often in younger people, and the median age of the participants in the trial was about 36 when the study began. Among the roughly two-thirds of participants with high-risk disease, 92 percent of those treated with ABVD alone were alive at 12 years, compared with 81 percent of those who received radiation therapy.

The rate of freedom from disease progression was lower in the group of patients treated with chemotherapy alone (87 percent) than in the group receiving radiation (92 percent), principal investigator Dr. Ralph M. Meyer, of the National Cancer Institute of Canada (NCIC) Clinical Trials Group, acknowledged at a press briefing on Sunday. 

"What we have shown is that ... chemotherapy [alone] improves overall survival, and it does so because there are fewer late effects than with a treatment strategy that includes radiation," Dr. Meyer said. "We have also shown that the standard paradigm of keeping the disease away being a proxy measure for living longer doesn't apply in this situation because of the late effects."

Most trials involving patients with stage IA or IIA Hodgkin lymphoma have followed the participants for 4 to 6 years and have used disease recurrence as the primary outcome measure, Dr. Meyer noted. However, late effects associated with radiation therapy do not become apparent for 10 years or more, he continued.

"The treatment of Hodgkin lymphoma today is a real balance between achieving control of the disease and cure while limiting long-term side effects," commented Dr. Jane N. Winter, who moderated the press briefing and is a past co-chair of the lymphoma committee of the Eastern Cooperative Oncology Group, which participated in the study. "This [study speaks] to that balance and [to] the importance of long-term follow-up in evaluating our new therapies."

The type of radiation therapy used in the study, known as subtotal nodal radiation therapy, is now considered outdated, added Dr. Meyer. "The treatment that the patients in the control arm received would today be considered excessive and likely contributed to the additional second cancers and cardiovascular events," he said. Although the risks of late effects associated with radiation therapy "are likely reduced with modern strategies, we don't know the magnitude by which they are reduced," he continued.

The NCIC trial results "confirm the known long-term detrimental effects of large-field radiation therapy, an approach that has long been abandoned given the large body of literature on the late effects of such treatment, and the similar efficacy of more limited radiation treatment fields as part of combined modality therapy," Drs. Peter Mauch and Andrea Ng, radiation oncologists at Harvard Medical School, wrote in an e-mail. Today, radiation doses are a fraction of those used in this trial, and treatment is limited to the area of the body affected by lymphoma, they explained.

"Clinical trials have shown that higher rates of recurrence are associated with increased mortality from Hodgkin lymphoma," Drs. Mauch and Ng continued. "The challenge is how to minimize recurrence while limiting the late mortality associated with treatment. Much has been achieved towards this goal with the use of reduced number of courses of chemotherapy and limiting the dose and field size of radiation."

Radiation oncologists have been divided over the role of radiation therapy in patients with stage IA or IIA Hodgkin lymphoma, said Dr. Richard Little of NCI's Cancer Therapy Evaluation Program. "Data from this study, which is the first published randomized trial with longer-term follow-up, will be taken by many to mean [that] omission of radiation therapy should be the standard of care in early-stage Hodgkin lymphoma," he said. "However, some patients and physicians will be so averse to the slight increase in early disease progression if radiotherapy is omitted that it will not be omitted in all cases."

Eleanor Mayfield

Cancer Research Highlights

Combination Therapy Shows Promise for Treating Advanced Breast Cancer

Adding the drug everolimus (Afinitor) to exemestane helped postmenopausal women whose advanced breast cancer had stopped responding to hormonal therapy live about 4 months longer without the disease progressing than women who received exemestane alone. Findings from the trial, called BOLERO 2, were presented last week at the San Antonio Breast Cancer Symposium.

For women who received the combination therapy, the median progression-free survival was 7.4 months compared with 3.2 months for those who received exemestane alone, Dr. Gabriel Hortobagyi of the University of Texas M. D. Anderson Cancer Center reported at the symposium. These were the latest available data, updated from preliminary results presented at the European Multidisciplinary Cancer Congress in September and results published online December 7 in the New England Journal of Medicine (NEJM).

The researchers do not yet have data on whether the combination therapy improves overall survival, but they expect to have it in late 2012. In July, the randomized phase of BOLERO 2 was stopped early after an interim analysis showed an improvement in progression-free survival. The study, which was supported by Novartis, the manufacturer of Afinitor, included many participants who had previously received multiple therapies.

Everolimus inhibits a protein called mTOR, which plays a role in a signaling pathway that promotes cell growth and proliferation. Exemestane, an aromatase inhibitor, is used to treat metastatic breast cancer.

“For postmenopausal patients with hormone receptor-positive metastatic breast cancer, the addition of everolimus to exemestane markedly improves the duration of disease control,” Dr. Hortobagyi said in a statement. This benefit should be weighed against the side effects associated with everolimus, such as fatigue and oral mucositis, the study authors noted in the NEJM article.

Most Common Adult Muscular Dystrophy Linked to Increased Cancer Risk

Adults with myotonic muscular dystrophy (MMD), an inherited disorder marked by progressive muscle wasting and weakness, may be at increased risk of developing cancer, a new study suggests. A research team led by Dr. Mark H. Greene and Dr. Shahinaz M. Gadalla, both of the Clinical Genetics Branch in NCI’s Division of Cancer Epidemiology and Genetics, found that patients with MMD from two independent cohorts had a twofold higher overall risk of cancer compared with people in the general population, with the increased risk mainly accounted for by cancers of the colon, brain, endometrium, and ovary. The results were reported in the December 14 issue of JAMA.

MMD is the most common form of muscular dystrophy that begins in adulthood. There are two types of MMD, type 1 and type 2, which affect multiple body systems and are caused by mutations in different genes. The signs and symptoms of the two types overlap, although type 1 is more severe.

“The impetus for this work came from [coauthor] Dr. Richard Moxley’s clinical impression that the cancer occurrence among his MMD patients was greater than expected,” Dr. Greene noted. The question then was whether those cancers were part of the MMD syndrome or just a coincidental finding.

To address this question, the researchers linked the health records of 1,658 MMD patients from two nationwide patient registries, one in Sweden and one in Denmark, to the corresponding national cancer registry in each country. They found the same patterns of increased cancer risk in both the Swedish and Danish MMD cohorts, which “provides substantial reassurance that our observations are genuine,” the study authors wrote.

“This study is the first formal quantitative assessment of cancer risk in MMD, which previously has not been considered a cancer susceptibility disorder,” Dr. Greene said.

“We don’t yet know for sure why MMD patients are at increased risk of cancer,” added Dr. Gadalla. “It may be that some of the genetic changes that cause MMD symptoms are also responsible for the increase in cancer risk.” Further research to explore the possible mechanisms involved may provide new insights into mechanisms of carcinogenesis, she noted.

In addition to pursuing that avenue of research, Dr. Greene and his colleagues are investigating whether the cancer risk differs between patients with type 1 versus type 2 MMD, and whether the excess risk can be explained by known risk factors for cancer—questions that this study could not answer.

In the meantime, Dr. Greene said, “It’s important that clinicians be aware of this possible increased risk of cancer in MMD patients.”

Two Drugs that Hit One Target Show Efficacy against Metastatic Breast Cancer

Combining two drugs that target the HER2 protein, trastuzumab (Herceptin) and the investigational agent pertuzumab, with chemotherapy may be a new treatment option for women with HER2-positive metastatic breast cancer, according to results from a large clinical trial.

The phase III CLEOPATRA trial showed that combining both of the HER2-targeting agents with the chemotherapy drug docetaxel as an initial treatment led to a 6-month improvement in progression-free survival compared to treatment with docetaxel and trastuzumab alone. The results were presented at the San Antonio Breast Cancer Symposium and published in the New England Journal of Medicine last week.

Targeting HER2 with two different drugs has shown promise in multiple trials, said the trial’s lead investigator, Dr. José Baselga of Harvard Medical School and the Massachusetts General Hospital, during a press briefing. “I think dual HER2 blockade is coming soon, and it will be in our daily practices.”

Although both drugs target the HER2 protein on the surface of cancer cells, they do so in different ways. Laboratory studies have indicated that the drugs may have a synergistic effect on HER2-positive tumors, which Dr. Baselga explained, are “addicted” to HER2 signaling.

More than 800 women were enrolled in the randomized trial; half received all three drugs and half received trastuzumab and docetaxel, a standard first-line treatment for women with metastatic HER2-positive breast cancer, plus a placebo. Progression-free survival was 18.5 months in the three-drug arm and 12.4 months in the two-drug plus placebo arm. More women who received the three-drug combination experienced significant shrinkage of their tumors than women who received trastuzumab, docetaxel, and the placebo, Dr. Baselga reported.

Although there is a trend toward better overall survival in women treated with pertuzumab, the trial hasn’t been running long enough to clearly determine whether the three-drug combination helps women live longer, Dr. Baselga said.

Trastuzumab has been associated with significant cardiac side effects in some women, but no  increase in such side effects was seen in women in the trial who received both HER2-targeted drugs.

Genentech, which manufactures pertuzumab and trastuzumab and funded the trial, has submitted an application to the Food and Drug Administration for approval of pertuzumab for use as an initial treatment in women with HER2-positive metastatic breast cancer.

Prostate Cancer Trials Show No Link between Androgen-Deprivation Therapy and Cardiac Deaths

Several studies have suggested that men who receive androgen-deprivation therapy (ADT) to treat prostate cancer may face an increased risk of dying from cardiovascular causes. But a new analysis of clinical trial results has found no evidence that ADT increases cardiovascular deaths among men with high-risk, nonmetastatic prostate cancer.
The findings, from a meta-analysis of eight randomized clinical trials, appeared in the December 7 issue of JAMA. Androgen-deprivation therapy, which suppresses the production of male hormones, is a mainstay of prostate cancer care. A form of ADT known as gonadotropin-releasing hormone agonist therapy has been linked to heart disease in some, but not all, studies.

Citing these studies, the Food and Drug Administration last year issued a safety warning for this class of drugs. Several medical societies have also issued a science advisory stating that there may be a relationship between ADT and cardiovascular events and death.

To explore this question further, Dr. Paul Nguyen of Dana-Farber Cancer Institute and his colleagues analyzed data on more than 4,000 participants in ADT trials. Among 2,200 men treated with ADT, there were 255 cardiovascular deaths (an overall incidence rate of 11.0 percent); among 1,941 men in the control groups, there were 252 deaths (11.2 percent).

The study also showed a benefit: Men who received ADT had a lower risk of dying from prostate cancer and other causes of death than men who did not. “Our study should be reassuring to most men with high-risk prostate cancer considering ADT,” noted Dr. Nguyen.

The main caveat of the study is that the researchers could not assess the risk of cardiac death for specific subgroups of patients, including those at highest risk for cardiovascular disease. Therefore, Dr. Nguyen said, “our study could not rule out the possibility that men with a history of cardiac disease could still be harmed by ADT.”

For men with significant underlying cardiac disease, the study authors recommend a careful examination by a cardiologist and a discussion of the risks and benefits of ADT.

Although ADT is not new, doctors are still learning about its risks and benefits, noted the authors of an accompanying editorial. Some research, for example, has suggested that ADT may shorten the time before a cardiovascular event occurs. (The current study could not address this question.)

To answer such questions, future prospective trials involving ADT should classify patients according to cardiovascular risk factors at the beginning of a study, noted the study’s senior author, Dr. Toni Choueiri of Dana-Farber Cancer Institute.

“While it is important to raise awareness of the possible cardiac side effects of ADT, it may be the case that the pendulum had swung too far away from the use of ADT, even for men with high-risk disease in whom ADT has been shown to save lives,” Dr. Choueiri wrote in an e-mail.

Guest Commentary by Secretary Kathleen Sebelius

mHealth Summit Keynote Address 

Secretary Kathleen Sebelius Secretary Kathleen Sebelius

The Honorable Kathleen Sebelius is the 21st secretary of the Department of Health and Human Services, which includes NCI. Secretary Sebelius delivered the following remarks at the mHealth Summit on December 5 in Washington, DC. The goal of the summit is to bring together leaders in government, business, clinical research, academia, and other areas to advance collaboration in the use of wireless technology to improve health outcomes in the United States.

Since I was here in 2009, few fields have undergone such rapid change as mHealth. Virtually every American today has a cell phone. Some of us have to carry two. And every year, our phones have more features and computing power. This year, for the first time ever, smart phones accounted for more than half of all phone sales in the US. 

As our phones get more powerful, they are becoming our primary tools for doing everything from getting directions to deciding where to eat. And increasingly, that includes using our phones to track, manage, and improve our health. In the iTunes store alone, there are nearly 12,000 different apps related to health — a number that will probably have gone up by the time I finish speaking.

As a technology story, this is hardly big news. Mobile phones have been playing a growing part of our lives for years. What is exciting about this change is that it's happening in an area where the rate of innovation has frankly been much slower.

Over the last few decades, we've seen information technology improve the consumer experience in almost every area of our lives. We've gone from waiting until a bank opened to make a deposit to 24-hour ATMs and paying bills online. But health care has stubbornly held onto its cabinets and hanging files.

When innovation is slow, so is improvement. As a result, in a country with the world's best doctors and nurses, its most advanced medical technology, its finest research institutions, and its highest health spending — Americans live sicker and die sooner than the people of many other nations around the world. 

At the same time, doctors are frustrated by a health care system that has put increasing demands on them while making it harder to practice the way they want. And rapidly rising health care costs have put an enormous burden on the budgets of families and businesses while forcing increasingly difficult choices at the federal, state, and local levels.

Part of our health care problem is a lack of information. Patients have little access to their own health information, which is usually stored out of their sight on charts in doctor's offices and pharmacy computer systems. Even basic information about where to find a good specialist or the side effects of a medication can be hard to obtain. And doctors often have incomplete information about their patients too, whether it's the fact that they just came from an emergency room or whether they're sticking to their diabetes regimen.

 Electronic health record use has doubled since January 2009 and is on pace to triple, bringing huge benefits to patients across the country.

It's with this information deficit in mind that the President launched a historic effort in the first month of his Presidency to speed up the adoption of electronic health records. And last week, I was pleased to announce that since then, the share of office-based doctors using electronic health records has risen from 17 percent to 34 percent, with 52 percent of doctors saying they intend to adopt them soon. In other words, electronic health record use has doubled and is on pace to triple, bringing huge benefits to patients across the country. 

Mobile health is the natural extension of this trend, bringing health information from people's computers to their pockets and purses. The advantage of mobile phones is that they're always with us. That's especially true for many of the groups that can otherwise be hard to reach like African Americans, Latinos, and young people. This also makes cell phones an incredible tool for empowering consumers to take control of their own health.

Now, there are some parts of our health that most of us are happy to leave in the hands of the professionals. We don't want to be involved in performing our open heart surgery. We're happy to leave the scalpels and lasers in the hands of our surgeons.

But there are other aspects of health where we not only want to be involved — we have to be involved. Eating a healthy diet, managing our diabetes, choosing a doctor, quitting smoking — these are all areas that require us to take charge of our own health.

And it's been incredibly inspiring over the last few years to watch developers in this room and across the country come up with tools that are helping people do just that. From iTriage, which makes finding a local care facility as easy as finding a local lunch spot, to Pillbox, which helps people quickly identify unlabeled medications, you're making it easier for Americans get the right information at the right time to make the right health decisions.

It's not just patients. Today, technologies built for consumers like iPads are finding their way into lab coat pockets, and a smart phone loaded with Epocrates is almost as much of a requirement for new doctors as a stethoscope. 

Perhaps most important of all, mobile technologies are opening up new lines of communication: between patients and their doctors, among health care providers trying to stay on the same page and even among communities of patients.

These innovations hold out the promise of a future with far more control for Americans and their doctors over their health. Still, I believe everyone here would acknowledge that we have a long way to go to fulfill that promise. So what we in the Obama Administration have asked is: what can we do to help accelerate the development of this transformative technology?

Let me be clear: there is no more powerful force for innovation than American entrepreneurs. Government couldn't replace the private sector as the primary force behind developing new products if it tried. And we don't want to try. 

But government can play a limited but crucial role as a catalyst. And electronic health records are a perfect example.

When this Administration came into office in 2009, less than one in five doctors used even a basic electronic health record. The benefits of health information technology for improving care coordination, minimizing errors, and reducing paperwork were well known. Nearly every other industry had embraced information technology. But adoption rates for electronic health records were barely budging.

We thought we could help change that. So as part of the Recovery Act, we made a series of investments targeted at the obstacles that were slowing the technology's spread. We created regional extension centers to help small doctor's offices that had no IT departments. We invested in health information exchange to address compatibility concerns. And we provided incentive payments to help offset the significant upfront costs of switching over.

And the results speak for themselves. As I mentioned earlier, not only has electronic health record use among doctors doubled. It's on pace to triple. And we've also created 50,000 new jobs in the field since we started.

When government targets its resources effectively, it can play a critical role in creating the conditions for innovation to thrive. And that's what we want to do with mobile health too.

That starts with taking the vast amounts of public health, medical, and other data our department collects and making it available to innovators. This data can be an incredible resource. But until recently, most of it was hidden from the public — scattered across hundreds of websites or publications, stored in unusable formats, and often locked behind pay walls.

So what we did is, unlock the data, put it in a central clearinghouse called, and then told developers: have at it. And the response so far has been incredible. Today, our data is being used in dozens of apps for consumers and providers. And we're just getting started.

We're also shining a spotlight on health problems that mobile developers can help solve. Earlier this year, for example, the Vice President and I challenged developers to come up with innovative apps that could help young adults protect themselves against dating violence and abuse. And today, I want to congratulate the two winners of our Apps Against Abuse challenge — Circle of 6 and On Watch — both of which are powerful new tools to help young people stay safe.

 Providers have a new menu of options they can choose from that allow them to focus more of their energy on keeping their patients healthy.

In addition, we're working directly on mobile health projects, from text4baby, which has provided over 250,000 moms with free health text messages, to a program we're announcing today called SmokeFreeTXT that's using text messaging to help teens quit smoking. And I've created a task force that is exploring additional opportunities to use mobile health technologies in areas like diabetes education, asthma management, and emergency preparedness.

But perhaps the biggest way we can make a difference is by continuing our work to improve our health care system. As you know, today's health care system often penalizes doctors who spend more time with their patients or take extra time to coordinate care with specialists. It often discourages investing in prevention or engaging patients in their own care.

That's bad for patients and doctors. And under the health care law, we're making some changes. Today, providers have a new menu of options they can choose from that allow them to focus more of their energy on keeping their patients healthy. There are shared savings programs that allow doctors and nurses to benefit when they help patients manage their chronic conditions and stay out of the emergency room. Another new program will help them improve coordination during care transitions so that patients who leave the hospital don't have to come back.

All these efforts can benefit from mobile health technologies. But the mobile health industry will also benefit from improving the health care system. Any change that empowers patients and encourages providers to work more closely together also creates more demand for your products. 

So today, my first challenge to you is to be supporters of all the innovations underway in our health care system, not just those that directly involve mobile tools. If you want mobile health technologies to succeed, the best thing you can do is help move us towards the kind of patient-centered health care system that allows those technologies to make the biggest impact.

But there's a second part to my challenge too. We all know these technologies will only be embraced if consumers know they are safe and that their health information will be secure. So today, I'm asking you to work with us to deliver on these promises. We're working hard at the FDA today to practice smart regulation that promotes safety and innovation.

 When we talk about mobile health, we are talking about taking the biggest technology breakthrough of our time and using it to take on one of the greatest national challenges of our time.

And we're also working to ensure that mobile devices come with full protections on patient privacy — a valid concern given that a large share of reported data breaches happen because health information on mobile devices was unencrypted. For mobile devices to flourish, we'll need your help, guidance, and support in both of these areas.

This is an incredible time to be having this conversation. When we talk about mobile health, we are talking about taking the biggest technology breakthrough of our time and using it to take on one of the greatest national challenges of our time. And while we have a way to go, we can already imagine a remarkable future in which control over your health is always within hand's reach.

We can imagine a future where you take a video of a rash on your foot and get a diagnosis later that afternoon without needing to schedule a doctor's appointment. A future where you keep a healthy weight with a phone that uses a motion sensor to calculate how many calories you've burned and estimates how many calories are on your plate by snapping a picture. A future where you get an automatic reminder that it's time for your next mammogram, text back to confirm your appointment, and schedule the test without any doctor or office staff lifting a finger. A future where taking care of your health is something you do with the help of your doctor every day, not just once a year at an appointment.

And I'd add to that a future in which these products are developed right here in the US and exported to countries around the world. As countries like China and India get richer, their health care spending will rise rapidly and so will their demand for technologies that can improve health and care. The question is not whether they'll buy mobile health technologies. It's who they'll buy them from. And there's no reason the answer shouldn't be the United States.

This future is not here yet, but it is within sight. And I look forward to working with you to achieve it.

Thank you.


Kathleen Sebelius

Secretary of Health and Human Services

A Conversation With

A Conversation with Dr. Barry Kramer about Cancer Prevention Research at NCI

Dr. Barry KramerDr. Barry Kramer

Dr. Barry Kramer was appointed director of NCI's Division of Cancer Prevention (DCP) on November 6. Dr. Kramer previously served as director of the NIH Office of Disease Prevention from 2001 to 2010. He has been the editor-in-chief of NCI's Physician Data Query Screening and Prevention Editorial Board since the early 1990s. He is also an investigator with the National Lung Screening Trial and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).

DCP supports research in cancer prevention and cancer screening. These two often get lumped together, but they're really two different things, aren't they?

Yes. When we talk about prevention, we mean lowering the risk of developing a disease. When we talk about early detection and screening—for most tests in most types of cancer—we're not talking about preventing cancer or lowering the risk of developing cancer, but detecting it early at a treatable stage and changing the outcome.

But there is an overlap in that some screening tests pick up tissue abnormalities before they become cancer—tissue changes that can be treated before they progress to cancer. The classic example, of course, is cervical cancer screening, where we consider it almost a failure of the system if you pick up a cancer, because the true goal is to pick up intraepithelial neoplasia or intraepithelial lesions well before they progress to cancer, treat them, and prevent cancer in the first place.

Another example is screening for colon cancer using endoscopy. We are looking for cancers, so we're not preventing those that are already there. But we're also trying to pick up polyps and neoplasia that could have progressed to cancer but that we can prevent from doing so by removing them.

What do you see as the greatest challenges in cancer prevention and screening?

One of the biggest challenges to prevention is identifying effective agents that prevent cancer but that are also very, very safe. When you're dealing with prevention, you're dealing with healthy people, and it's very difficult to make a healthy person better off than they already are. And that's why you can't accept very much toxicity at all when you are intervening on very large numbers of healthy people. So an active area of research will be to find [chemoprevention] agents that are effective but not toxic.

In screening, one of the big challenges is overdiagnosis, which is when screening tests detect lesions that never would have caused a health problem had they not been detected. The classic example is prostate cancer screening, where there's a large reservoir of silent disease, much of which would never cause a medical problem. If you employ a screening test, you will dip into that reservoir of tumors that wouldn't have caused harm, and you can actually trigger harm [through] some very intensive, but unnecessary, therapy.

So there are three important areas [of research] for DCP in terms of screening. One is figuring out the net benefits and harms of screening tests. The second is that, if someone has chosen to be screened and they have a screen-detected cancer, we have to figure out which people benefit from treatment and which don't. An area of active research for DCP, through the Early Detection Research Network, will be looking for molecular patterns that identify tumors that will not progress.

Third, there are cancers that come up in the interval between screening tests. Those are the cancers you really need to prevent. These cancers tend to be aggressive, because they grow so quickly between screening tests. And so we need to look at the molecular patterns in these tumors as well, to identify pathways that might serve as targets for preventive agents. 

What do you think are the most exciting areas for current research in cancer prevention and screening?

We've known for years that obesity is associated with an elevated risk of a variety of cancers. We don't know exactly why, and we need to study why, but we know it's been difficult to have people lose weight or maintain ideal body weight, and, with the increasing prevalence of obesity, we have to figure out the mechanistic links between obesity and cancer.

There's emerging evidence that the gut microbiome—the microorganisms that live in our gut—participates in digestion and energy exchange. And there's at least some evidence in animal models that the gut microbiome helps determine an animal's weight. So it's an exciting area of research, to see if our microbiomes are also linked to energy exchange, food absorption, nutritional balance, and pathways that serve as drivers for cancer.

Then, of course, we have to look for and test new potential screening tests. Some of the screening tests out there are not of proven value, and we need to identify which ones may have value, and identify the ones that are promising enough to put into definitive trials.

Finally, we're excited about immunologic approaches to preventing cancer. Any cancer that is caused by an infectious agent could potentially be a target for primary prevention with a vaccine. We obviously have some very important vaccines already, like the human papillomavirus (HPV) vaccines, which people are now improving to cover a broader spectrum of cancer-causing HPV types. That would be a major breakthrough, if we could prevent most or all of the HPV infections that cause cancer.

Will there likely be more large-scale prevention or screening clinical trials like PLCO?

We need to know what works and doesn't work, and it takes large randomized trials to establish net benefit—or harm. Many assumed that vitamins can't have any harm, and we're learning through large trials like the Selenium and Vitamin E Cancer Prevention Trial (SELECT) that they can. SELECT gave a disappointing result, but it's important to know that vitamin E may be associated with an increased risk and not a decreased risk of prostate cancer. It's equally important to know that beta-carotene increases the risk of death in heavy smokers, which we learned from the Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study.

On the plus side, tamoxifen and raloxifene were both proven to decrease the risk of breast cancer, so there have been positive outcomes as well as negative outcomes from large trials—but all are equally important. And the National Lung Screening Trial showed for the first time ever that a screening test can decrease the risk of dying of lung cancer in heavy smokers and former smokers. So there have been notable successes in the area of prevention and screening [trials].

Given the economy, however, it's now hard to launch very large trials, so we have to be selective, and we have to figure out when something is ready for prime time, for definitive testing. We have to get a better handle on what type of evidence it would take to justify a large clinical trial, and that's another area of ongoing investigation in the division.

Interview by Sharon Reynolds

Special Report

Panel Encourages Broader Use of Surveillance in Some Men with Prostate Cancer

Artwork from the NIH State-of-the-Science Conference: Role of Active Surveillance in the Management of Men with Localized Prostate CancerAn independent panel of experts met December 5–7 at an NIH-sponsored state-of-the-science conference on the role of active surveillance in the management of men with localized prostate cancer.

An independent panel of experts has endorsed delaying treatment, at least for a time, for many men who are diagnosed with forms of prostate cancer that likely pose no risk to long-term health.

Forgoing immediate treatment with surgery or radiation, both of which can have serious side effects, and instead actively monitoring the disease is a "viable option" for many men diagnosed with low-risk prostate cancer, the panel concluded in a draft statement from the NIH-sponsored state-of-the-science conference.

The large majority of men diagnosed each year with low-risk prostate cancer opt for immediate treatment with surgery or radiation. Both treatments can produce side effects that can seriously impair a man's quality of life, including erectile dysfunction and incontinence. Even so, in the United States only about 10 percent of men diagnosed with low-risk prostate cancer choose some form of observation.

The prognosis for men diagnosed with low-risk prostate cancer is so good, the panel concluded, that "strong consideration should be given to removing the anxiety-provoking term 'cancer' for this condition." Avoiding the term in these cases could encourage fewer men to pursue immediate treatment, several panel members suggested.

Evidence-Based Approach

NIH convened the conference to assess data supporting active surveillance, the observation-first approach most commonly used in the United States for selected men with low-risk prostate cancer. Due to widespread screening with the prostate-specific antigen (PSA) test, low-risk prostate cancers now account for the majority of diagnosed cases. Active surveillance involves monitoring the cancer with PSA testing, digital rectal examination, and biopsies at routine intervals and initiating treatment with curative intent only if and when these monitoring techniques indicate that the disease may be progressing.

Defining Prostate Cancer Risk

The most recent clinical guidelines on prostate cancer from the National Comprehensive Cancer Network define very-low risk and low-risk disease as follows:

Very-low risk

  • Clinical stage T1c (no palpable disease, biopsy recommended based on abnormal PSA)
  • Gleason score of 6 or less
  • PSA density (ratio of PSA level to prostate gland size) of 0.15 ng/mL/cc or less
  • Two or fewer biopsy cores in which cancer is present, and less than 50 percent cancer present in any involved core

Low risk

  • Clinical stage T1-T2a
  • Gleason score 2-6
  • PSA < 10 ng/mL

Based on studies showing similar survival outcomes compared with immediate treatment, active surveillance has been recommended for men with low-risk or very low-risk prostate cancer, depending on their life expectancy. Categorizations such as low-risk disease are based on the PSA score at diagnosis, the grade of the tumor's aggressiveness (Gleason score), and to what extent tumor cells are found in needle biopsy samples taken from the prostate.

"We estimate that more than 100,000 men diagnosed with prostate cancer each year in the United States would be candidates for active monitoring rather than immediate treatment," said the panel chair, Dr. Patricia Ganz of UCLA's Jonsson Comprehensive Cancer Center.

The conference covered a wide range of topics, such as how evolving pathology practices have affected tumor grading and the potential economic implications if more men diagnosed with prostate cancer were to pursue an observation-first approach.

A number of important questions remain about active monitoring approaches, the panel wrote. It's still unclear, for example, how best to carry out these observation-first protocols, including the frequency of biopsies, which carry their own risks. Effective approaches are still needed to improve the process by which patients interact with physicians to reach treatment decisions, panel members said, including informed discussions about options such as active surveillance.

Assessing the Evidence

Only two clinical trials comparing an observation-first approach with immediate treatment have been completed and both involved watchful waiting—that is, no routine monitoring and only initiating treatment to alleviate symptoms. The studies supporting active surveillance, on the other hand, have been observational.

The clinical trials presented at the conference produced conflicting results. The first, a Swedish trial, found that immediate treatment reduced the risk of prostate cancer death. But many men in the trial, only about 5 percent of whom were diagnosed by screening, had higher-risk disease than men considered to be candidates for observation-first approaches in the United States, acknowledged the trial's lead investigator, Dr. Lars Holmberg of King's College School of Medicine in London.

In a yet-to-be published U.S. trial, the Prostate Intervention Versus Observation Trial (PIVOT), however, overall and prostate-cancer specific mortality were very similar for low-risk men whether treated with watchful waiting or immediate surgery. About half of the men in this trial had their cancer diagnosed following a PSA screening test, and 40 percent were categorized as having low-risk disease.

"These are the men being treated in the United States today," said PIVOT's lead investigator, Dr. Timothy Wilt of the Veterans Affairs Center for Chronic Disease Outcomes Research in Minneapolis, MN. "Our data suggest that observation is the preferred option in men with low-risk disease."

Several large active surveillance programs are under way in North America, and although the programs are similar in most respects, they vary somewhat with regard to monitoring procedures and treatment triggers.

Despite the differences, very few prostate cancer deaths have occurred across these programs. For example, of the more than 650 men who have participated in the University of California, San Francisco's active surveillance program, none have died from prostate cancer, said the program's leader, Dr. Peter Carroll. Sixty-four percent of participants have lived at least 5 years without switching to active treatment. While most of the men in the program have low-risk disease, a small percentage of men have higher-risk disease.

Although some men will never require treatment, Dr. Carroll stressed that the aim of active surveillance is to delay treatment—and its potential side effects—as long as possible. "It's not treatment versus no treatment," he said. "That's important."

A modest proportion of men in the large active surveillance programs drop out, choosing to have surgery or radiation despite no evidence that their cancer is progressing. To understand why men make these decisions, research is needed on the role of factors such as anxiety and family pressures, the panel concluded. Future studies should compare the effectiveness of different active surveillance protocols, the panel recommended.

Several studies suggest that physician recommendation is perhaps the strongest factor driving men's treatment decisions. But a patient's role, and his reaction to a cancer diagnosis, shouldn't be discounted, said panel member Dr. Barry Kogan, chair of the Division of Urology at Albany Medical College.

"The word 'cancer' tends to set off an emotional response in patients," Dr. Kogan said, "that encourages them to pursue what they perceive to be the most effective treatment regimen."

Carmen Phillips

A videocast of the conference is available online.



Institute of Medicine Releases Report on Breast Cancer and the Environment

Breast Cancer and the Environment: A Life Course Approach cover The Institute of Medicine released a report on December 7 reviewing the current evidence on breast cancer and the environment.

On December 7, the Institute of Medicine (IOM) released a report called Breast Cancer and the Environment: A Life Course Approach at the 2011 San Antonio Breast Cancer Symposium. The scientific advisory board of the breast cancer organization Susan G. Komen for the Cure commissioned the report, which involved 20 months of research by a committee of 15 experts in the field.

The committee was asked "to review current evidence on the contribution of environmental exposures to breast cancer, either alone or in combination with genetic factors, and to review the challenges in conducting this kind of research," explained committee chair Dr. Irva Hertz-Picciotto of the University of California, Davis, at a press conference announcing the report's release. The Komen advisory board also asked the committee to explore "evidence-based actions that women could take to reduce their risk and to recommend research for the future," she continued.

The committee defined "environmental exposures" as all factors that are not directly inherited through DNA. It found strong evidence for several commonly identified risk factors for breast cancer, including ionizing radiation, estrogen-progestin hormone therapy in postmenopausal women, and being overweight after menopause. The conclusions also identified physical activity as potentially protective against breast cancer and outlined a set of actions women can take that may reduce their risk. 

"Some of the strongest evidence that the committee reviewed was the increased risk of breast cancer in association with ionizing radiation. Since medical diagnostic x-rays are an increasingly common source of radiation, especially in young women, the committee emphasized the importance of limiting exposure to diagnostic x-rays to situations of proven benefit and the monitoring of cumulative doses of radiation," said Dr. Barry Kramer, director of NCI's Division of Cancer Prevention and a member of the IOM committee.

Actions that May Reduce the Risk of Breast Cancer

  • Avoid inappropriate exposure to medical radiation.
  • Avoid combination menopausal hormone therapy, unless medically appropriate.
  • Avoid or stop smoking.
  • Limit or eliminate alcohol consumption.
  • Maintain or increase physical activity.
  • Maintain healthy weight or achieve healthy weight to reduce postmenopausal risk.
  • Limit or eliminate workplace, consumer, and environmental exposure to chemicals that are plausible contributors to breast cancer risk while considering risks of substitutes.
  • If at high risk of breast cancer, consider use of chemoprevention.

From Breast Cancer and the Environment: A Life Course Approach

The committee emphasized that the concern over medical radiation exposure mainly focuses on high-dose procedures, such as some types of CT scans. Other common medical procedures, such as mammograms and dental x-rays, use low doses of ionizing radiation, and the committee stressed that they are not recommending that women avoid these low-dose procedures when medically recommended.

"Evidence suggests that women may have substantial opportunities to reduce their risk of breast cancer…[though] the potential risk reduction that these actions could bring for any individual woman will vary, and they may be small or…moderate," said Dr. Picciotto.

Women also run the risk, explained the committee members, that an action taken to reduce the risk of breast cancer may inadvertently raise the risk of other disease. Some of these trade-offs are known; for example, the drug tamoxifen, which can decrease the risk of breast cancer, also increases the risk of endometrial cancer. Other trade-offs are not yet understood, such as whether avoiding exposure to a chemical suspected of having cancer-causing properties, such as bisphenol A (BPA), could lead to exposure to other chemicals with equal or greater risks.

Directions for Research

The report emphasizes that there are many challenges to studying breast cancer risk, including the possibility that some exposures that may influence risk occur early in a woman's life, even in utero. The report recommends examining exposures at all stages of life, not just during adulthood, as well as taking a multidisciplinary approach to studies of breast cancer risk. It also emphasizes developing new methods for epidemiologic research, for accurately assessing exposure to potential risk factors, and for testing the cancer risk of chemicals and other substances.

Because data from human studies are often unavailable or inconclusive, the committee did not find strong evidence linking many suspected chemicals to breast cancer risk; only exposures to benzene, 1,3-butadiene, and ethylene oxide had "possible association[s]" with increased breast cancer risk. Several other chemicals, including BPA, had "biological plausibility as a hazard," but no human studies have confirmed an association with cancer risk.

"Traditionally, many of the cancer bioassays that have been done [in animal models]…started exposures early in life, but not at a very young age nor in utero or during the major period of breast growth," said Dr. David Eaton, a committee member from the University of Washington. "More modern-day testing…does take into account the life stage, but it's important to recognize that many of the chemicals tested in the past did not include early-life exposures that might be important."

"Some … vulnerabilities to environmental exposures only occur in very early periods of life, like during development," agreed committee member Dr. Cheryl Lyn Walker from Texas A&M Health Science Center.

"If we think about the ideal study, it would be to develop a cohort of individuals from birth, and follow them across their [lives]," added Dr. Robert Hiatt, a committee member from the University of California, San Francisco. Since such cohort studies are unlikely to be done for cost and other reasons, better integration between animal models and human epidemiologic studies are needed, he said.

Other Advisory Efforts Under Way

The National Institute of Environmental Health Sciences (NIEHS), in collaboration with NCI, is also examining future directions for research on environmental and genetic factors related to breast cancer. In September 2010, the congressionally mandated 19-member Interagency Breast Cancer and Environmental Research Coordinating Committee (IBCERCC) began to review all breast cancer research efforts conducted or supported by federal agencies.

"Both [the IOM and IBCERCC] reports will include a review of the state of the science regarding breast cancer and the environment and recommendations for future research, but the IBCERCC was called upon to make recommendations about how to coordinate and facilitate research efforts on environmental factors and breast cancer risks across federal agencies and with other research partners," explained Dr. Debbie Winn, deputy director of NCI's Division of Cancer Control and Population Sciences, who is leading NCI's effort on the IBCERCC.

"We are thoroughly examining prior reports, especially authoritative reviews and evaluations such as this IOM report, as we develop our recommendations," she added. The IBCERCC hopes to release its results by early summer 2012.

Sharon Reynolds

A Closer Look

Cancer Clinical Trials System Restructuring Moves Forward

The restructuring of NCI's clinical trials program took another step forward last month when NCI's Board of Scientific Advisors (BSA) approved a proposal to fund a new integrated NCI Clinical Trials Network (NCTN). The proposal builds on existing efforts at NCI to enhance the efficacy and efficiency of the clinical trials program.

Graphic showing the structure of NCI's clinical trials programThe Coordinating Center for Clinical Trials (CCCT) facilitates a dialogue among the institute's various divisions, offices, and centers, represented by CTROC, and the extramural clinical and translational research communities, represented by CTAC. [Enlarge]

Under the proposal, NCI would fund no more than five clinical trials groups (up to four adult groups and one pediatric group), as well as centers to provide support for core services, such as imaging and radiation therapy. The funding would also support investigators whose focus will be on incorporating molecular research studies and other translational research into NCTN trials.

The proposed restructuring aims to enhance the participation of NCI-designated cancer centers and other leading academic medical centers in NCTN clinical trials. A cornerstone of this effort is higher per-patient reimbursement from NCI for high-performing centers, that is, centers that meet performance benchmarks in areas such as accrual to clinical treatment trials and data quality.

According to a timeline presented during the meeting, NCI and NIH will review and refine the proposal through early 2012, with the expectation that funding announcements for participation in the network will be released by the summer of 2012. Grants for network participation will be awarded in the spring of 2014.

Responding to the Call

Goals for NCI Clinical Trials System
  • Improve the speed and efficiency of trial development and conduct.
  • Incorporate innovative science and trial design.
  • Improve trial prioritization, selection, support, and completion.
  • Ensure participation of patients and physicians in the system.

Although questions were raised about the proposal at the BSA meeting, such as whether the restructuring would affect the role of advocates in the system and access to genomic data, BSA members welcomed the proposal, saying it addresses many of the issues that have been raised by numerous groups and that were highlighted in a 2010 Institute of Medicine (IOM) report commissioned by NCI.

A more integrated, streamlined clinical trials system will help provide answers to pressing clinical questions sooner and more efficiently than has been possible in the past, said Dr. Michael Caligiuri, director of the Ohio State University Comprehensive Cancer Center, who chaired a BSA subcommittee on restructuring the clinical trials system. "This will allow us to get to the goal line more quickly," Dr. Caligiuri said. "That's how we cure cancer."

The restructuring is centered around the four overarching goals for the program laid out in the IOM report and by numerous stakeholders in the NCI clinical trials program, such as improving the speed and efficiency with which trials are developed and conducted, explained Dr. Margaret Mooney, chief of the Clinical Investigations Branch in NCI's Division of Cancer Treatment and Diagnosis (DCTD).

Consensus Goals for a Transformed NCI Clinical Trials System

Through existing efforts, such as tight adherence to timelines for progress in certain areas, the time it takes to launch a trial has already been cut in half. Further improvements should be possible, said Dr. Jeff Abrams, acting director of clinical research in DCTD.

One component that should help trials run more efficiently is a common patient data management system that is currently being implemented. All sites participating in future network clinical trials will use this single electronic system to capture and transmit patient data, which Dr. Mooney said can also provide benefits in areas such as data analysis and regulatory compliance.

Consolidation Has Begun

In response to the IOM report and NCI's announced intention to fund fewer groups under NCI's new network clinical trials program, the existing cooperative groups have already begun to merge.

Earlier this year, the Cancer and Leukemia Group B, North Central Cancer Treatment Group, and American College of Surgeons Oncology Group announced that they were merging to form the Alliance for Clinical Trials in Oncology. The American College of Radiology Imaging Network and the Eastern Cooperative Oncology Group are also merging, as are the National Surgical Adjuvant Breast and Bowel Project, Radiation Therapy Oncology Group, and Gynecologic Oncology Group.

A key facet of the proposal is the consolidation of the clinical trials groups from 10 to no more than 5—a process that has already begun. This consolidation should help to improve recruitment, reduce redundancies, and provide economies of scale in areas such as information technology systems and regulatory activities, according to Dr. Mooney.

Just as important, new review criteria for clinical trial approval will likely translate into more trials for cancer types that have been typically underrepresented relative to their incidence, Dr. Mooney noted. A new subcommittee of NCI's Clinical Trials and Translational Research Advisory Committee will be charged with ensuring that important opportunities to address less common tumors "are not missed," she added.

Greater Cancer Center Involvement

Committee members were particularly pleased with the proposal to increase reimbursement to centers for enrolling patients in NCTN trials. Although health care costs have risen dramatically, far outstripping standard inflation, per-patient reimbursement for NCI cooperative group trials has remained at $2,000 for the last decade. Reimbursement for industry-sponsored trials is often three to five times that amount.

Under the proposal, per-patient reimbursement would rise by $2,000 for high-performing centers. The reimbursement increase is desperately needed, said Dr. Robert Diasio, director of the Mayo Clinic Cancer Center, during the BSA meeting. Low reimbursement has "made it completely unrealistic for many [cancer centers] to participate" in NCI cooperative group trials, he said.

Covering the higher reimbursement within the trial network's proposed budget, however, will mean that fewer patients will be enrolled in network group trials—a decline from approximately 25,000 patients enrolled annually to about 20,000.

"Increasing reimbursement means we'll have to focus even harder on prioritizing what trials we go forward with," Dr. Mooney said.

Cancer centers and other academic centers will also be able to compete for grants called U10 awards that will be awarded and managed by principal investigators at individual centers. Under the current system, such grants are managed through the individual cooperative groups with which cancer centers are aligned. In the integrated network, investigators at academic centers that receive the U10 awards have an incentive to enroll patients in any open network group trial, Dr. Caligiuri stressed.

With this approach, "the patient gets a smorgasbord of trials to choose from, regardless of which group is leading the trial," he continued, "and the investigator has every incentive to place patients on the trials that are most appropriate for them."

Carmen Phillips

For more information, watch a videocast of the recent BSA meeting on the NIH website.

Featured Clinical Trial

Comparing Postoperative Radiation Therapies for Brain Metastases

Name of the Trial
Phase III Randomized Study of Post-Surgical Stereotactic Radiosurgery Versus Whole-Brain Radiotherapy in Patients with Resected Metastatic Brain Metastases (NCCTG-N107C). See the protocol summary.

Dr. Paul Brown Dr. Paul Brown

Principal Investigator
Dr. Paul Brown, North Central Cancer Treatment Group

Why This Trial Is Important
Cancer that spreads from the site of an original, or primary, tumor to other parts of the body is called metastatic cancer. Although there are exceptions, metastatic cancer is usually incurable and often leads to death. Treatment for metastatic cancer is usually given in an attempt to delay further progression of the disease, prolong life, and/or alleviate symptoms.  

Metastatic cancer may spread anywhere in the body, but the lungs, liver, bones, and brain are commonly affected. Metastatic tumors in the brain (brain metastases) are usually treated with radiation therapy alone, but occasionally these tumors can be removed (resected) with surgery. Surgical resection may improve survival, but, unfortunately, recurrence is common.

Therefore, whole-brain radiotherapy (WBRT) is usually used after surgery in an attempt to improve tumor control. Although the use of WBRT has been associated with improved tumor control, studies have not shown that it improves patient survival. In addition, WBRT can decrease long-term neurocognitive functioning, severely affecting a patient's quality of life.

Recently, doctors have begun using a different type of radiation therapy—stereotactic radiosurgery—following surgical resection of brain metastases. Stereotactic radiosurgery directs a large amount of radiation in one single treatment to the area where a tumor was resected, whereas WBRT delivers radiation to the entire brain in small doses, or fractions, over a period of several weeks.

In this clinical trial, patients with one to four brain metastases who have had at least one of the metastatic tumors removed surgically will be randomly assigned to undergo WBRT or stereotactic radiosurgery. Doctors will assess the effects of these treatments on overall survival and neurocognitive functioning. They will also monitor the patients for quality of life, functional independence, adverse events, and tumor recurrence.

"Brain metastasis is the most common cancer diagnosis in the brain and is several fold more frequent than the most common primary brain cancer," said Dr. Brown. "So brain metastases are a significant problem in oncology.

"Whole-brain radiotherapy has been the standard of care for brain metastases, but recently there's been a growing interest in radiosurgery to the surgical bed because you can irradiate just the surgical bed and potentially reduce the side effects," Dr. Brown explained. "The issue with radiosurgery to the surgical bed is there is very little literature supporting its use, and we don't know how effective it is compared to whole-brain radiotherapy. This trial, which is being conducted in collaboration with other NCI cooperative groups, will provide that head-to-head comparison to the standard of care, whole-brain radiotherapy."

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

Community Update

Communications This article is part of a series of stories related to cancer communications. You can read more articles in the series here.

Cancer News Workshop Helps Latin American and U.S. Journalists Interpret Research Results

The second annual Inter-American Workshop for Scientific Journalism on cancer research, co-sponsored by NCI and held last month in Guadalajara, Mexico, drew 38 journalists from seven Latin American countries and 2 journalists from Hispanic media outlets in the United States. They came to learn how to more accurately evaluate and report on the impact of cancer in their communities and present cancer research findings on screening and new treatments.

Twice the number of reporters and editors attended this year compared with last year's workshop in Brazil, noted Nelvis Castro, associate director of Multicultural and International Communications at NCI. Attendees were also more diverse this year, representing newspaper, radio, and TV outlets from some of Latin America's largest cities, she said. Participants came from Argentina, Brazil, Chile, Costa Rica, El Salvador, Mexico, the United States, and Uruguay.

Participants at the Inter-American Workshop for Scientific Journalism Latin American journalists learned how best to report on cancer research at the workshop.

The workshop, which was made possible with support from Mexico's Universidad de Guadalajara and Universidad de Sonora, is held in conjunction with the annual meeting of the United States–Latin America Cancer Research Network (US–LA CRN), which was launched in 2009 by the NCI Office of Latin American Cancer Program Development (OLACPD). The US–LA CRN is a research partnership involving NCI and the governments and biomedical institutions of five Latin American countries: Argentina, Brazil, Chile, Mexico, and Uruguay. Its mission is to collaborate on state-of-the-art cancer research in Latin America.

This year, the program committee honed the workshop agenda to better meet the needs of the attendees, Castro said. Unlike the 2010 workshop, "we had mostly Spanish-speaking presenters this year, including for all of the scientific presentations," she said. That included Dr. Marcia Cruz-Correa of the University of Puerto Rico Comprehensive Cancer Center, who spoke on cancer screening studies; Dr. Ignacio Miguel Musé Servrini of Uruguay's Programa Nacional de Control del Cáncer, who addressed cancer in Latin America; and Dr. Antonio Tito Fojo, head of the Experimental Therapeutics Section in NCI's Center for Cancer Research.

This year's agenda also paired each scientific presenter with seasoned Latin American or U.S. health care and cancer journalists, who offered a different perspective on the cancer research topics. Whereas the scientific speakers focused on providing accurate and engaging accounts of the latest research developments, the journalists talked about "their unique approaches to covering that research area, and shared tools and tips they use to decide if a study is newsworthy and where to go for expert advice in making that evaluation," Castro explained. The journalists providing this expert guidance were Valeria Román, a senior science reporter with the Clarin newspaper in Buenos Aires, Argentina, and Dr. Ivan Oransky, the executive editor of Reuters Health.

The attendees also heard a presentation by's Gary Schwitzer, on how to systematically evaluate research studies and other data and findings before reporting on study results.

After each session, the journalists took part in an educational group activity, led by the session speakers, to apply what they learned. "I liked the balance between lectures and hands-on work," commented Alfredo Monferré of the Fundación Instituto Leloir in Argentina. "I think the workshop accomplished its aim, and many people left hungry for more, which is a good note to end on."

A number of the reporters published articles about the conference and the US–LA CRN when they returned home, Castro noted.

"The workshop was a fantastic opportunity to learn how to better understand and evaluate the scientific evidence and renew our commitment to covering cancer news," Román said. "The mix of perspectives—from scientists to journalists and from people who live in different countries—also helped us to feel that we are not isolated when we face the challenges of informing our citizens about cancer research."

NCI plans to host another cancer research journalism workshop in 2012, Castro said. The goal is to expand and attract writers and editors from even more diverse areas of Latin America, from outside the capital cities and from "new media" outlets, as the Internet and digital information revolution penetrate farther into the region. Workshop organizers also hope to create a network of workshop alumni to foster continued communication and dissemination of new information among journalists in Latin America, taking advantage of social media platforms such as Facebook, Twitter, and LinkedIn.

Bill Robinson


In Memoriam: Lloyd Old, Cancer Immunology Pioneer

Dr. Lloyd Old (Photo courtesy of Cancer Research Institute) Dr. Lloyd Old (Photo courtesy of Cancer Research Institute)

Dr. Lloyd Old, a pioneer in cancer immunology, died November 28 of prostate cancer at the age of 78. Over the course of his career, Dr. Old made several groundbreaking discoveries that led to a deeper understanding of how the body's own immune system can be used to kill cancer cells.

When Dr. Old started his research in the 1950s, cancer immunotherapy was in its infancy. In large part due to his perseverance, the field is now considered one of the most promising areas for cancer research. Last spring, the Food and Drug Administration approved two immunotherapies for cancer—sipuleucel-T (Provenge) for some prostate cancers and ipilimumab (Yervoy) for metastatic melanoma. These drugs might not have been developed without the discoveries Dr. Old made decades ago.

Dr. Old is perhaps best known for the 1975 discovery with Elizabeth Carswell of tumor necrosis factor (TNF), a protein that can boost the immune response and can also cause some types of tumor cells to die.

Dr. Old also played an important role in several other discoveries. In 1979, he was one of several researchers to identify protein 53 (p53). The gene for p53 is a tumor suppressor that is mutated in roughly half of all cancers. In addition, in 1959 Dr. Old and Dr. Baruj Benacerraf showed that bacillus Calmette-Guerin, a tuberculosis vaccine, could provide some protection against tumors in mouse models. Since the 1990s, the vaccine has been used as a first-line treatment for superficial bladder cancer.

Dr. Old spent his career at Memorial Sloan-Kettering Cancer Center, the Ludwig Institute for Cancer Research, and the Cancer Research Institute. He was elected to the National Academy of Sciences in 1978 and served on several scientific advisory boards and committees, including ones at NCI.

Barbara Rimer and Owen Witte to Join the President's Cancer Panel

Drs. Barbara Rimer and Owen Witte Drs. Barbara Rimer and
Owen Witte

On November 29, President Barack Obama announced his intent to appoint Dr. Barbara K. Rimer and Dr. Owen N. Witte to the President's Cancer Panel. Dr. Rimer would chair the three-person advisory committee, which monitors the development and execution of activities of the National Cancer Program. Each year, the panel holds a series of meetings and writes a report to the president on a topic of concern in the cancer community. Panel members serve 3-year terms, and the appointment of the third member is pending.

Dr. Rimer is dean of the Gillings School of Global Public Health at the University of North Carolina at Chapel Hill, where she has been a faculty member and member of the Lineberger Comprehensive Cancer Center since 2003. From 1994 to 1997 she was the first woman to chair NCI's National Cancer Advisory Board, and from 1997 to 2002 she served as director of NCI's Division of Cancer Control and Population Sciences. Dr. Rimer received the NIH Director's Award and the American Cancer Society's Distinguished Service Award and was elected to the Institute of Medicine in 2008. She received a B.A. and M.P.H. from the University of Michigan and a Dr.PH. from the Johns Hopkins Bloomberg School of Public Health.

Dr. Witte is director of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at the University of California, Los Angeles (UCLA). From 2005 to 2007, he served as the founding director of UCLA's Institute for Stem Cell Biology and Medicine. Dr. Witte first joined the UCLA faculty in 1980 and has been an investigator at the Howard Hughes Medical Institute since 1986. He has served on a number of boards, including the board of the American Association for Cancer Research. He is also a member of the National Academy of Sciences, the American Academy of Arts and Sciences, and the Institute of Medicine. He holds a B.S. from Cornell University and an M.D. from Stanford University School of Medicine.

National Cancer Advisory Board Holds Final Meeting of 2011

The National Cancer Advisory Board (NCAB) held its last meeting of 2011 in Bethesda, MD, on December 5–6. NCI Director Dr. Harold Varmus, Deputy Director Dr. Doug Lowy, and Deputy Director for Clinical and Translational Research Dr. James Doroshow presented the NCI director's report.

Dr. Barbara Wold gave an overview of the Center for Cancer Genomics, and Dr. Barry Kramer discussed the recent U.S. Preventive Services Task Force recommendation on PSA testing.

In addition, researchers from NCI's Center for Cancer Research gave presentations on the origins of the xenotropic murine leukemia virus-related virus (XMRV) and new approaches for intramural-extramural collaborations.

Other presentations were delivered by researchers from the Division of Cancer Epidemiology and Genetics who spoke about the risks of bladder cancer related to smoking, findings from the NCI Costa Rica HPV-16/18 vaccine trial, the aging genome and its relationship to cancer, and adverse health outcomes in women exposed in utero to diethylstilbestrol.

The full agenda and a videocast of the meeting are available online.

Toby Hecht Appointed Associate Director of Translational Research Program

Dr. Toby Hecht Dr. Toby Hecht

Dr. Toby T. Hecht was recently appointed associate director of the Translational Research Program in the NCI Division of Cancer Treatment and Diagnosis (DCTD), after serving as acting associate director for the past 4 years. 

The Translational Research Program oversees the Specialized Programs of Research Excellence (SPOREs)—P50 grants that emphasize a team science approach to organ-site translational cancer research. During more than 25 years at NCI, Dr. Hecht has managed programmatic activities and developed biological agents, taking them from the lab bench to the clinic. Her research background is in immunology and immunotherapy

NCI Launches Text Message Service to Help Teens Quit Smoking

Cell phone

A new initiative to help teens quit smoking will employ something that many young people use every day—the mobile phone. SmokefreeTXT is a free text-message service that provides encouragement, advice, and tips to teens trying to quit smoking.

Once they sign up, teens will receive text messages timed according to their selected smoking quit date. Following their quit date, they will continue receiving texts for up to 6 weeks. This is a critical piece of the SmokefreeTXT service, since research shows that support is important beyond the first few weeks of quitting. Teens can sign up online or text QUIT to iQUIT (47848).

Nearly 20 percent of teens smoke, and most will continue smoking into adulthood unless efforts are made to help them quit. By connecting with teen smokers on their mobile phones, NCI hopes to help young people quit with proven tools and strategies.

"With 75 percent of youths between the ages of 12 and 17 owning a cell phone, there is immense potential for mobile technologies to affect health awareness and behavior change among teens," said Dr. Erik Augustson, a behavioral scientist in NCI's Tobacco Control Research Branch.

SmokefreeTXT, a key component of the Department of Health and Human Services' efforts to develop mobile health programs, is one of the core features of the new Smokefree Teen initiative, an extension of NCI's smoking cessation website,

Smokefree Teen, a site specifically developed to help teen smokers quit, also offers several social media pages to connect teens with cessation tools. In January 2012, Smokefree Teen will launch a free smartphone application, QuitSTART—an interactive quit guide for teens that delivers cessation and mood management tips, tracks cravings, and monitors quit attempts.

Radiation Epidemiology and Dosimetry Course Available Online

The 2011 Radiation Epidemiology and Dosimetry course, presented by NCI's Division of Cancer Epidemiology and Genetics, is now available online. The course is intended for people with a background in epidemiology who are interested in learning about the health effects of radiation exposure, particularly the relationship between ionizing radiation and cancer.

The course consists of video presentations on radiation chemistry and biology, DNA damage and susceptibility to radiation, studies of irradiated populations, nuclear incidents and accidents, studies in medically irradiated populations, and nonionizing radiation. Handouts are also available and may be downloaded.

Funding Available to Support Collaborations between U.S. and Chinese Scientists

NIH and the National Natural Science Foundation of China (NSFC) recently published corresponding funding announcements to encourage and support research cooperation between U.S. and Chinese scientists studying cancer, mental health, allergy, immunology, and infectious diseases, including HIV/AIDS and its comorbidities. NIH released an announcement for administrative supplements for U.S. investigators, and NSFC published an announcement for new 1-year projects from Chinese collaborating investigators. This initiative is part of a U.S.–China Program for Biomedical Research Cooperation that was established by NIH and NSFC in 2010.

U.S. and Chinese investigators will work together to develop corresponding applications to NIH and NSFC. Applications will be reviewed in parallel by both agencies using similar selection factors, and funding decisions will be made by both agencies according to research priorities of both countries. NIH has pledged to support up to $4 million in total costs in FY 2012 under this program, whereas NSFC has indicated that approximately 300,000 renminbi (about $47,000) will be available per project to support Chinese collaborators.