National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
July 26, 2011 • Volume 8 / Number 15
Special Issue: Cancer and Obesity Research


Dr. Brandon Hayes-Lattin

Toward a New Understanding of Cancers in Adolescents and Young Adults

by Dr. Brandon Hayes-Lattin

My personal motivation to improve the understanding and care of cancer among adolescents and young adults (AYAs) comes from reflection on my own diagnosis of a prototypical young adult cancer, testicular cancer, at age 28. Read more > >



  • FDA Update

    • Advisory Panel Recommends Accelerated Approval for Brentuximab
  • Notes

    • NCI Director to Hold Town Hall Meeting
    • NCI Translational Science Meeting Sessions to Be Videocast
    • Thai Princess Signs Agreement with NCI
    • NCI's Early Detection Research Network Wins NASA Award
    • Noted Author and Oncologist Siddhartha Mukherjee Speaks at NIH Article contains video
    • Latest Issue of CCR Connections Released


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

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

For more information about cancer, call 1-800-4-CANCER or visit

NCI Cancer Bulletin staff can be reached at

Guest Commentary by Dr. Brandon Hayes-Lattin

Toward a New Understanding of Cancers in Adolescents and Young Adults

Dr. Brandon Hayes-Lattin Dr. Brandon Hayes-Lattin

My personal motivation to improve the understanding and care of cancer among adolescents and young adults (AYAs) comes from reflection on my own diagnosis of a prototypical young adult cancer, testicular cancer, at age 28.

Having just begun my training as an academic oncologist, I found myself asking a wide range of questions: Why does testicular cancer predominantly affect young adults? Why is there a separate disease staging system in the pediatric versus the adult clinic? How does a young adult balance a cancer diagnosis with a new career and a new family?  What resources exist to support young adults during their cancer journey? How does a cancer diagnosis affect long-term survivorship?

Striving to answer these questions led me to form the Adolescent and Young Adult Oncology program in the Knight Cancer Institute at Oregon Health and Science University and to work with the Lance Armstrong Foundation's LIVESTRONG Young Adult Alliance.

More than 72,000 adolescents and young adults (ages 15 to 39) learn they have cancer each year in the United States, a number up to seven times larger than the number diagnosed under the age of 15. Cancers that are common in AYAs often are rare in the traditional adult oncology clinic—germ cell tumors, leukemias and lymphomas, melanoma, thyroid cancer, and sarcomas.

AYAs face unique medical issues. For instance, diagnosis is often delayed because physicians rarely think of a young adult as having cancer. A lack of health insurance also makes access to medical care more difficult for some patients in this age range, although the new health care law that allows children to stay on their parents' insurance until the age of 26 should help in this regard.

Sometimes AYA patients receive treatments that may not be the most effective for their cancer. For instance, recent clinical trials indicate that, in at least some cases, AYA patients with acute lymphoblastic leukemia (ALL) may have better outcomes when treated with pediatric, rather than adult, regimens. Young adults also face issues around the availability and timing of fertility preservation techniques and often report a sense of isolation within the traditional pediatric or adult cancer clinic setting, where they see very few other patients their own age.

Until recently, many physicians have been unaware of these issues, compounding the difficulties faced by young people with cancer. Perhaps as a result of this lack of awareness and other factors, survival rates for AYAs have stagnated in recent decades, while survival rates for young children and older adults have improved.

The report of NCI's Adolescent and Young Adult Oncology Progress Review Group, published in 2006, provided the stimulus, the legitimacy, and the framework to pursue work in AYA oncology. The report, titled "Closing the Gap: Research and Care Imperatives for Adolescents and Young Adults with Cancer," presented five key recommendations for improving outcomes:

  1. Characterizing the distinguishing features of the AYA cancer burden. More research is needed on the biology of tumors in AYA patients given that, in some types of cancer, tumors appear to be different from those in children and older adults. These biological differences may require different treatment regimens to achieve the best possible outcomes. In addition, more research is needed to understand the psychosocial effects of diagnosis, treatment, and survivorship in this age group, and how intellectual, emotional, cultural, and other factors influence medical outcomes.

  2. Providing education and training. Health care providers who work with AYAs must be educated about the types of cancers that occur most commonly among this age group, monitoring for late effects among survivors, and the psychosocial needs of AYA patients and survivors. Broader public and professional education campaigns are also needed to raise awareness about AYA cancers in general and risk factors in particular.

  3. Creating tools to study AYA cancers. The report recommended creating a database on all AYA cancer patients, increasing the number of tissue samples available for research from this population, and expanding the number of clinical trials appropriate for and available to AYAs.

  4. Ensuring excellence in care delivery. The first step toward achieving this goal is the development of standards of care for AYA patients. Once these standards have been developed, they must be disseminated to and implemented by all stakeholders in the AYA community, including researchers, health care providers, and advocates.

  5. Bolstering advocacy and support. Effective support services for AYA cancer patients and survivors need to be based on an understanding of how cancer may affect their self esteem, spirituality, body image, life goals, and stage of development, among other factors.

In the 5 years since these goals were set, we have made progress in each area. Research projects have been started, tissue samples collected and analyzed, and clinical trials focused on AYAs launched. Preliminary work laying the foundation for standards of care has been completed.

In the area of awareness and education, programs and workshops for health care providers have been set up and advocacy groups are spreading the word. In the past year, LIVESTRONG has partnered with the American Society of Clinical Oncology to produce the "Focus Under Forty" educational series.

I believe that understanding "outlying" cancers such as those occurring in the AYA age range will lead to new treatments and more supportive approaches to care. We have seen examples in applying pediatric principles to the treatment of young adult ALL, characterization of and differing treatment approaches for premenopausal breast cancer, and genetic screening for early-onset colorectal cancers.

As an oncologist, a cancer researcher, and a survivor of cancer as a young adult, I am proud of the work aimed at improving outcomes for AYA patients, encouraged by the spirit of collaboration to continue seeking answers to the questions I faced, and eager to participate in these continued efforts.

Dr. Brandon Hayes-Lattin
Medical Director, AYA Oncology Program, Knight Cancer Institute, 
    Oregon Health and Science University

Senior Medical Advisor, Lance Armstrong Foundation


Health Insurance Poses a Hurdle for Many AYA Survivors

Obtaining health insurance can be a major challenge for survivors of AYA cancers. And the importance of having insurance is becoming clearer. A recent study led by Dr. Jackie Casillas of UCLA's Jonsson Comprehensive Cancer Center, for example, found that adult survivors of childhood cancers without health insurance were much less likely to receive general preventive care or cancer survivorship-focused care than survivors their age with private or public insurance.

Many will "age out" of coverage under their parents' insurance, noted Dr. Smita Bhatia of City of Hope Cancer Center, and, because of their health history, many are priced out of the private insurance market.

Although survivors can often obtain insurance through school or work, even these routes can be difficult, explained Dr. Julia Rowland, director of NCI's Office of Cancer Survivorship. She noted that "these policies can be quite limited, especially when it comes to the high costs of dealing with a serious illness that calls for close monitoring and can result in chronic health challenges over time."

In addition, because many survivors suffer late effects, including cognitive deficiencies, "completing school and getting a job can be a major challenge," Dr. Bhatia said.

For Matt Sasaki, 21, of Sacramento, CA, a leukemia survivor, the chronic pain caused by avascular necrosis, a deteriorative bone condition, has altered his life in ways he hadn't imagined. "[The avascular necrosis] is so painful and distressing, I am not in school or working," he explained. Insurance issues, he continued, have limited his ability to seek treatment.

The health care reform law enacted last year should help some AYAs dealing with late effects, Dr. Rowland noted. Under the Affordable Care Act, for example, young adults up to age 26 can remain on their parents' health insurance plans. The portability and pre-existing conditions provisions in the law "can also help to reduce the number of AYAs who might otherwise be without insurance," she said.

Carmen Phillips

Special Issue: Adolescents and Young Adult Cancer

Uncovering the Biology of Cancers in Adolescents and Young Adults

The first scientific journal dedicated to cancers in adolescents and young adults (AYAs) published its first issue in March, marking a milestone for the emerging field of AYA oncology. But as experts noted in a roundtable discussion in the issue, the field faces many challenges, particularly when it comes to understanding the biology of these diseases.

At one point in the conversation, Dr. Archie Bleyer of the St. Charles Regional Cancer Center in Bend, OR, shared a concern about the state of the science. "My concern, most of all, is that we have not understood the biology of these diseases because we have not researched them thoroughly enough," said Dr. Bleyer. "And therefore we may not know how to treat them as well as we could."

The participants agreed that a lack of tumor samples for study has slowed progress. Most specimens are collected during clinical trials, and AYAs have long been underrepresented in the limited number of trials open to them, though this may be changing.

Lymphoblasts from bone marrow (Image courtesy of Dr. Charles Mullighan) Lymphoblasts (leukemic cells in ALL) from bone marrow. (Image courtesy of Dr. Charles Mullighan)

Although the biology of AYA cancers is poorly understood, recent evidence suggests that some of these diseases may have unique genetic and biological features. Much of the research to date has involved acute lymphoblastic leukemia (ALL), which is the most common pediatric cancer but also occurs in teens and young adults.

"We now have more evidence that there are distinct AYA subtypes of ALL, though the genomics of these subtypes needs to be clarified," said Dr. Bleyer, who is also a clinical research professor at Oregon Health and Science University.

He cited work done by Dr. Christine Harrison of Newcastle University in the United Kingdom. Her team of researchers found that some AYAs with ALL have genetic changes that are typical of younger patients, whereas others have previously unknown alterations.

Profiling Tumors

A clearer picture could emerge from a genomic analysis of more than 500 tumors from AYAs with ALL. The study, now under way, extends a recent analysis of tumors from children with ALL to teens and young adults.

This study is a major first step toward understanding how the biology of ALL differs between early childhood and early adulthood, noted Dr. Stephen Hunger of Children's Hospital Colorado and the University of Colorado School of Medicine. He also chairs the ALL committee of the Children's Oncology Group.

We think the spectrum of genetic lesions in ALL changes with age.

—Dr. Cheryl Willman

Some clues have already emerged from this work, according to Dr. Cheryl Willman, director of the University of New Mexico Cancer Center and a leader of the study. For instance, some AYA tumors have genetic alterations that are often seen in older children with ALL who are at high risk of relapse. (AYAs and high-risk older pediatric patients tend to have worse outcomes than the vast majority of younger children with ALL.)

"We're very interested in the final results," said Dr. Nita Seibel of the Clinical Investigations Branch in NCI's Cancer Therapy Evaluation Program. "The analysis could support the premise that ALL in AYAs is a different disease than what we see in pediatrics, where the cancer tends to respond to treatments."

The first phase of the AYA genomic profiling study is nearly complete. "We should have results to share in approximately 3 months," co-leader Dr. Charles Mullighan of St. Jude Children's Research Hospital wrote in an e-mail.

Discovering Potential Targets

By focusing on patients with poor outcomes, Drs. Mullighan and Willman and their colleagues have tried to elucidate the biology of these diseases and identify potential therapeutic targets.

The strategy appears to be paying off. In the pediatric study (part of the Childhood Cancer TARGET Initiative), the researchers identified cancer-related mutations in members of the JAK kinase gene family, along with other alterations. Mutations that increase the activity of JAK proteins have been seen in several cancers, and drugs that inhibit JAK are in early-phase clinical trials.

"The discovery of these mutations has allowed us to develop clinical trials of targeted therapies that we hope will improve the care of these patients," said Dr. Willman. Eventually, the researchers would like to analyze the genomes of adult tumors and compare the age groups.

"We think the spectrum of genetic lesions in the disease changes with age," said Dr. Willman, noting that ALL could be a model for investigating other AYA cancers.

A Workshop on AYA Biology

Breast scan A recent study found few age-specific differences in the biology of breast tumors.

Two years ago, NCI and the Lance Armstrong Foundation convened a workshop on the biology of cancers in AYAs. The meeting focused on ALL, as well as breast and colorectal cancers, and there was no clear consensus about whether these diseases have distinct biological features.

"At the time, the best evidence for a biological difference was in colorectal cancer, but some of that evidence was from small studies that were limited in scope," said Dr. James V. Tricoli of NCI's Cancer Diagnosis Program and a co-author of a recent commentary about the meeting. "None of the evidence was clear-cut," he added.

The authors of the commentary agree with many in the field that more research is needed on the underlying biology of AYA cancers. It will also be important to learn whether these differences influence the clinical behavior of these cancers, they added.

"We need to understand the biology of the disease to ensure that we're giving patients the most appropriate treatment without over-treating them," said Dr. Anna Franklin, medical director of the Adolescent and Young Adult Program at the University of Texas M. D. Anderson Cancer Center. Other nonbiological factors may also influence outcomes, such as compliance with treatment and the unique psychological and social issues facing AYA patients.

In colorectal cancer, she noted, the standard treatments are designed for older patients, and these regimens may not be the most effective in young adults where the disease may have a distinct biology. Dr. Franklin is starting a study of colorectal cancer biology in young adults. The study, done with colleagues at M. D. Anderson and the University of Colorado, will compare different biologic features of tumors from younger and older patients, using freshly collected tissue and samples from tumor banks.   

In breast cancer, few, if any, molecular differences have been identified in AYA patients that could distinguish these tumors from those that arise later in life.

"Most of the evidence [at the workshop] suggested that there were relatively few unique molecular differences in breast cancers that occur in the younger age group compared to when the disease occurs in older women," noted Dr. Donald Blair of NCI's Division of Cancer Biology.

This conclusion was supported by a recent study that also found few age-specific differences in the biology of breast tumors. Age alone, the study authors concluded, "does not appear to provide an additional layer of biologic complexity" above that of the particular subtype and grade of breast cancer.

But younger women are more commonly diagnosed with more aggressive breast cancer subtypes than their older counterparts, noted the study's lead author, Dr. Carey Anders of the UNC Lineberger Comprehensive Cancer Center. "At present, the reason for this difference is not completely understood and is certainly worthy of further study," she wrote in an e-mail.

Comparing Tumors in a Single Patient

Genomic approaches have also been used to investigate the biology of neuroblastoma, a cancer that arises in immature nerve cells. The disease primarily affects infants and children, but it can also occur in young adults. As with other AYA cancers, young adults tend to do worse than children.

"This disease in young adults is also very different biologically than the disease that occurs in childhood," said Dr. Javed Khan of the Pediatric Oncology Branch in NCI's Center for Cancer Research.

His group recently sequenced all of the protein-coding regions of the genome (known as the exome) in four samples from a 19-year-old woman with neuroblastoma whose cancer had spread to several organs. By comparing the exomes of normal cells, the primary tumor, and metastatic lesions, the researchers identified six potentially cancer-related mutations shared by the primary tumor and two metastases.

"The finding supports the hypothesis that all of the tumors originated from a common progenitor cell, and that few significant changes occurred during more than 3 years of treatment," said Dr. Khan. His group plans to publish the results this year.

Because of the poor outcomes associated with cancers in AYAs, more research is needed in this field, Dr. Khan added. He is planning a scientific meeting next year that will address the genomics of AYA cancers, particularly sarcomas.

Insights from Clinical Trials

Along with genomic studies, clinical trials will be critical for advances in treating AYA cancers, several researchers said. In ALL, for instance, prospective trials could help resolve a debate about whether AYAs with the disease should receive pediatric rather than adult regimens.

When does a younger adult become an older adult?

—Dr. Daniel DeAngelo

For a decade, researchers have known that some AYAs with ALL fare better when treated with pediatric regimens. These observations have come from retrospective analyses of clinical trials, however, and the reasons for the findings are unknown.

A prospective trial, CALGB-10403, could provide answers. This NCI-sponsored study is evaluating the effectiveness and side effects of a pediatric regimen in adolescents and young adults. "This is an important study because there has been debate over whether AYAs can tolerate the toxicities associated with pediatric-based approaches," said Dr. Seibel.

Prospective trials are also under way in Europe and at the Dana-Farber Cancer Institute, where pediatric ALL regimens have been the standard of care for patients between the ages of 1 and 50 since 2001.

Many doctors are hoping that the results of these studies will lead to a consensus about how to treat ALL in AYAs, noted Dr. Daniel J. DeAngelo, director of the adult leukemia clinic at Dana-Farber. He frequently receives phone calls from community doctors seeking advice about how to treat young adults.

"This question creates a lot of angst in the community," said Dr. DeAngelo. The National Comprehensive Cancer Network is reviewing the issue and will likely make a recommendation, he noted.

Provocative Questions

New Journal Focuses on AYA Oncology

A new journal dedicated to improving the care of AYA cancer patients and survivors was launched in May. The Journal of Adolescent and Young Adult Oncology will publish research on the biology and treatment of these diseases as well as on the psychosocial and survivorship issues facing AYAs. 

In addition, the journal will include forums on controversial issues in the rapidly evolving field. All articles in the first issue are available online free of charge.

Cover of the Journal of Adolescent and Young Adult Oncology

Meanwhile, the Dana-Farber group is trying to learn about the biology of ALL in AYAs. This work, they hope, will lead to a genetic or biological test that can identify, at the time of diagnosis, which young adults are most likely to respond to pediatric ALL regimens.

The researchers are also considering some provocative questions. "When does a younger adult become an older adult?" said Dr. DeAngelo. "We don't really have a handle on that yet."

As answers to this and other questions about AYA cancers emerge in the coming years, researchers can share their results in the Journal of Adolescent and Young Adult Oncology.

"I really believe we're going to prove in the years ahead that the biologic features of these cancers are different from the same cancers that arise in other age groups," said the journal's editor, Dr. Leonard Sender of the University of California, Irvine, and the Hyundai Cancer Institute at Children's Hospital of Orange County. "But we have to do the science."

Edward R. Winstead

Special Issue: Adolescents and Young Adult Cancer

Clinical Trials Offer a Path to Better Care for AYAs with Cancer

Family talking to nurse Some adolescents and young adults have family support to help them through cancer treatment, but many have to navigate the medical system on their own. Lack of a support system presents one of many barriers to enrollment in clinical trials for AYAs.

Survival of children with cancer has climbed dramatically in the last five decades, with 5-year survival rates of less than 10 percent 50 years ago and almost 80 percent today. At the same time, progress in treating adolescents and young adults (AYAs) has stagnated, with 5-year survival rates staying constant at about 70 percent over the last 30 years.

Twenty-five years ago, AYAs with cancer had a better prognosis overall than children with cancer, but this is no longer the case. For 20 of the most common types of cancer among AYAs, only eight have shown an improvement in survival since 1985.

Researchers attribute this lack of progress in part to the fact that relatively few AYAs participate in clinical trials, which have allowed pediatric oncologists to make such rapid advances in treatment for children. One of the main reasons that so few AYAs participate in clinical trials is that, even at major cancer centers, there are few clinical trials available to this age group.

For example, a 2007 study by Dr. Peter Shaw, head of the AYA oncology program at the Children's Hospital of Pittsburgh, and his colleagues found that, of the new patients diagnosed at their institution over a 5-year period, 38 percent of all children younger than 15 joined a trial, compared with 27 percent of older adolescents. Fifty-seven percent of the older group did not enroll in a trial because there were none available to them, wrote Dr. Shaw and his colleagues.

"Too little is known about AYA cancers, in large part because the patients are not on clinical trials," commented Dr. Nita Seibel, of the Clinical Investigations Branch in NCI's Cancer Therapy Evaluation Program. "And if the patients are not on these trials, then researchers cannot gather information about their treatment and survival, nor do they have tumor samples to try to understand the biology of their disease."

This opinion was similarly expressed in the 2006 report from the NCI/LIVESTRONG Adolescent and Young Adult Oncology Progress Review Group, which identified lack of participation in clinical trials as a factor limiting progress against cancer in this population.

Across the country, researchers are testing innovative ways to enroll more AYAs in clinical trials—and in the right clinical trials—using expanded access, patient navigation, community outreach, and collaborations between academic and community doctors.

Treating Them like Children

Several years ago, retrospective studies from researchers across the United States began hinting that, for many types of cancer, patients between the ages of 18 and 39 might do better when given pediatric treatment regimens than when given adult regimens.

One of the main reasons that so few AYAs participate in clinical trials is that, even at major cancer centers, there are few clinical trials available to this age group.

In a 2008 study in Blood, Dr. Wendy Stock, director of the leukemia program at the University of Chicago, and her colleagues looked at survival for more than 300 patients between the ages of 16 and 20 with acute lymphoblastic leukemia (ALL) who had been treated either in pediatric trials through the Children's Cancer Group (now part of the Children's Oncology Group; COG) or in adult ALL trials through the Cancer and Leukemia Group B (CALGB).

"We found that there was a significant difference in outcome favoring the treatment that the pediatricians were using," said Dr. Stock. Similar results have been seen in retrospective studies from France, the United Kingdom, and the Netherlands.

A separate retrospective study published in 2010 by researchers from St. Jude Children's Research Hospital showed a jump in cure rates for older adolescents with ALL who received a pediatric regimen that used drugs that are not traditionally given to older patients because of concerns about side effects.

Based on the results of their 2008 study, the University of Chicago researchers and colleagues from three adult cooperative groups—CALGB, the Eastern Cooperative Oncology Group, and the Southwest Oncology Group—have designed the first intergroup phase II clinical trial testing a pediatric treatment regimen for ALL in patients between the ages of 16 and 39. The trial has enrolled 200 of the 300 planned participants.

This study is at least as important for its cooperative nature as the hypothesis it is testing. "The model is that the U.S. trial groups are going to try to work together on young adult ALL trials, simply because [otherwise] there aren't enough AYA patients" to ask questions about different cancer subtypes, explained Dr. Stock.

Another trial is testing whether a pediatric regimen for Ewing sarcoma is effective in young adults. The study is recruiting through NCI's Cancer Trials Support Unit, a program that provides doctors access to cooperative group cancer trials when they or their medical centers are not members of a cooperative group. Most AYAs with cancer are not treated at academic medical centers but are seen by local oncologists, most of whom do not normally have direct access to cooperative group trials.

"It's not the first thought of most medical oncologists to reach out to a pediatric oncologist when the patient is in their late teens to early adulthood," said Dr. Shaw. "They may just think of [the patient] as a regular adult with cancer and not think that [he or she] would be eligible for a pediatric trial. Two miles away or even two buildings over, there might be a pediatric oncologist who's an investigator for a national COG study that could enroll their patient, and they just don't know to ask."

Navigating the World of Cancer

Interestingly, although researchers understand that some AYA patients benefit from treatment with pediatric regimens, they do not understand all the reasons why, said Dr. Stock. "We don't even know if the differences in treatment [regimens] are so significant. It may also be differences in compliance with treatment," she explained. "Pediatric oncologists have a better support network that is incorporated into the way they approach the care of a child with cancer."

Although the entire pediatric health system is built around the fact that the patients are not expected to be able to make their own decisions or to take an active role in their own care, the adult medical world, where AYAs tend to get most of their treatment, is predicated on the exact opposite—that patients want to take care of themselves and be their own advocates.

"Children get through these arduous treatments because their parents are there, pushing them to take their medications, making sure they get to their appointments," said Dr. Stock. "Older adults tend to have an established support network—family, friends, neighbors. Young adults, a lot of them have to do it on their own," she explained.

Some institutions are increasingly turning to patient navigators to make sure AYAs don't slip through the cracks during their care, whether they are receiving standard treatment or are enrolled in a clinical trial.

We think that a lot of the great success in pediatric cancer can be attributed to the involvement of the majority of pediatric patients on trials, and we think that if we applied those same principles to the young adult population, we would get more success.

—Elizabeth Saylor

"We think that a lot of the great success in pediatric cancer can be attributed to the involvement of the majority of pediatric patients on trials, and we think that if we applied those same principles to the young adult population, we would get more successes," said Elizabeth Saylor, a masters-prepared social worker and patient navigator with the Ulman Cancer Fund for Young Adults. She works in collaboration with the University of Maryland Greenebaum Cancer Center's social work staff and multidisciplinary medical teams to ensure support for young adult patients between the ages of 18 and 40.

In her daily duties, Saylor functions as a one-person AYA support team, doing everything possible to make sure patients, whether they are in a clinical trial or not, have access to the resources they need to keep their appointments. "We make sure people have their transportation squared away, make sure their phones are charged up with minutes so we can always reach them," she said.

Saylor also helps negotiate insurance coverage for trial participation—many young adults lack proper coverage—and even negotiate trial flexibility for patients, many of whom have young children of their own and may live far from the cancer center. "If there's some aspect of the trial they could get closer to home, at a regional cancer center or even in a physician's office, we try to figure out how that might be done," continued Saylor. "We try to do things that help young adults stay compliant with the trial but still [allow them to] live their lives."

Studies have shown that increased monitoring and support can improve treatment compliance on trials. For example, in their study testing the pediatric regimen for AYAs with ALL, the St. Jude researchers regularly tested participants' blood for the presence of drugs they were supposed to be taking on their own at home. When blood levels dropped, patients and their families were reminded of the importance of adhering to the treatment. After the reminder, blood levels usually went back up.

Bringing Trials to the Community, Bringing the Community to Trials

A major barrier to enrolling more AYAs in clinical trials remains their wide dispersion outside—and isolation from—the few academic centers that offer clinical trials for AYAs. "We can keep trying to fix the clinical trial problem, but we have to look at the bigger picture of how AYAs get their medical care. We can't fix the clinical trial problem outside of that," said Dr. Karen Albritton, former chair of COG's Adolescent and Young Adults Committee.

Many institutions are trying to bridge the communication barriers between academia and community physicians by providing dedicated programs for AYAs. Dr. Stock and her colleagues are trying to put together a weekly young adult clinic at their center "to create a hub for referrals for young adults. It's a unique demographic in terms of their psychosocial needs and economic issues," she said. "If we can create an environment that is supportive to that group of patients, and advertise it to the community as such, we might be better able to attract referrals and enroll patients on clinical trials."

Dr. Shaw has built an AYA program at the University of Pittsburgh in collaboration with his colleagues in the adult cancer center there, and he has recently begun reaching out to community physicians. "I try to talk about the benefits of collaboration for these patients. I don't want physicians to feel like I'm telling them that they don't know what they're doing," he said. "We just want them to be aware of the trial opportunities available and [how] to get their patients involved."

Dr. Albritton recently moved from the Dana-Farber Cancer Institute to Fort Worth, TX, to start a community-based AYA oncology program at Cook Children's Medical Center and the University of North Texas Health Science Center. "We're like a lot of towns across the country in that we have a pediatric center and several good hospitals staffed by private oncologists, but no unifying academic oncology program. How can we bring AYA-focused care to that kind of community setting?" she asked.

Their solution is to build a distributed program—not housed at any single center—that relies as much on community physicians as on the children's hospital, according to Dr. Albritton. "We have expertise that's going to be wasted if we don't share it with the community, but they have the patients, and they have knowledge and experience too, so we think we should all partner," she continued. 

"It's not going to be the 'Cook Children's AYA program.' It's the Fort Worth AYA program. This is an issue for all of us, and we don't want community physicians to feel like they're losing their patients if they send them to a trial. We think if we build this as a community, it will be a win-win situation for everyone."

Sharon Reynolds

The HOPE Study: Collecting Population-Based Data on AYAs with Cancer

In 2005, a Progress Review Group (PRG) supported by NCI and the Lance Armstrong Foundation was brought together to examine why there had been so little progress in improving survival rates in AYAs with cancer. The PRG's report was one of the first to spotlight the critical need for more research on AYA cancer patients and survivors.

One of the major research projects to emerge from the working group was a large cohort study called the Adolescent and Young Adult Health Outcomes and Patient Experience (AYA HOPE) study. Cancer is rare among AYAs, a diverse group that is often in the middle of important life transitions, making them tough to study. "It's challenging for researchers to get enough people in their studies to get the information they'd like to collect," explained Dr. Ashley Wilder Smith of NCI's Division of Cancer Control and Population Sciences.

A large population-based study is critical, Dr. Smith said, for researchers to better understand "where these patients are being treated, what kind of care they're getting, and what their experiences are during and after treatment."

AYA HOPE was designed as a feasibility study to determine how best to survey AYA cancer patients and survivors and to collect outpatient and inpatient medical records.

The study involved approximately 530 AYAs from seven of the cancer registries in NCI's Surveillance, Epidemiology, and End Results program. The original AYA HOPE study assessed patients 6 to 14 months after diagnosis; a follow-up survey was conducted about a year later.

The first report from the study, published earlier this year, showed that the type of information needed to adequately analyze AYA cancer survivors can be gathered, but doing so is not easy and requires a substantial amount of effort.

"This is the biggest population-based study done in this age group of cancer survivors, and it's going to give us an indication of some of our next steps," Dr. Smith said.

Other manuscripts from the AYA HOPE study are in development, she noted, including those on treatment, clinical trial involvement, health-related quality of life, and supportive care and informational needs.

Carmen Phillips

Special Issue: Adolescents and Young Adult Cancer

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

For Many Young Cancer Survivors, Late Effects Pose Lasting Problems

Karen Kinahan and Julia Stepenske Karen Kinahan (left) and Julia Stepenske at an event celebrating the STAR program's tenth anniversary. The STAR program provides comprehensive long-term care for adult survivors of childhood cancers at Northwestern University's Lurie Comprehensive Cancer Center.

"Last summer I was diagnosed with bilateral Avascular Necrosis in my hips from all of the prednisone I received throughout the years [of chemotherapy]. In the fall I had core decompression on my left hip and it was pretty useless in resolving my chronic bone pain.… Because of my age (21) my orthopedic surgeon does not want to perform hip replacement surgery and I feel like I'm sort of just stuck with the pain without any resolution."
—Post on forum

Cataracts, hearing loss, chronic pain, amputation, hypopituitarism, osteonecrosis—these are just a few of the many late effects of cancer and its treatment that survivors can experience. For survivors of adolescent and young adult (AYA) cancers, these conditions can mean a lifetime of disability. Survivors of AYA cancers, like their pediatric counterparts, are also at increased risk for life-threatening problems such as second primary cancers and cardiac conditions, as well as psychiatric issues such as post-traumatic stress disorder and depression.

Unfortunately, studies indicate that many survivors of AYA cancers are often unaware of or underestimate their heightened risk for late effects; the same is true of many of the doctors and health care providers these survivors see after leaving the confines of active cancer treatment and follow-up.

For a number of reasons, research on AYA survivors has lagged. With nearly 70,000 AYAs diagnosed with cancer every year, the dearth of data can have serious consequences. "Significant knowledge gaps impede the care of this high-risk population," Drs. Kevin Oeffinger and Emily Tonorezos of Memorial Sloan-Kettering Cancer Center recently wrote in Cancer.

But positive changes are afoot.

More pediatric hospitals and cancer centers, for example, have established units tailored to help survivors deal with the long-term and late effects of care. The Children's Oncology Group (COG) has also developed an array of resources, including clinical guidelines for monitoring and treating common late effects in pediatric and AYA cancer survivors. Various advocacy and support organizations—such as Planet Cancer and the I'm Too Young for This! Cancer Foundation, among others—have programs to help AYA patients and survivors.

And some studies have been launched to test different ways to reach out to AYA survivors and help them take the necessary steps to monitor their health and ensure that they don't exacerbate the risk of late effects.

"That's an important part of what we need to do—move on to intervention studies," said Dr. Greg Armstrong of St. Jude Children's Research Hospital. "We've described the problems. Now we need to test ways to step in and intervene on them."

Treatment Can Be a Life Saver and a Life Changer

Numerous studies, including many from the Childhood Cancer Survivor Study (CCSS), include AYA participants and "have opened up the black box of long-term survivorship by describing what it really looks like to be an adult survivor of not only childhood, but adolescent and young adult cancer," Dr. Armstrong said.

Just last month, a study from the CCSS led by Dr. Armstrong showed that survivors treated during childhood or adolescence have an increased risk of not just second cancers, but third and fourth cancers. The study also identified the development of nonmelanoma skin cancer as an important risk factor for new cancers in this population.

Such findings and studies are a step in the right direction. But what's also needed is a more sophisticated understanding of late effects in AYAs, stressed Dr. Jackie Casillas, a pediatric oncologist and associate director of the Patients and Survivors Program at the UCLA Jonsson Comprehensive Cancer Center.

"We need to understand what's happening at the biological level that produces these late effects," she said. A better understanding of the biological mechanisms by which treatments are causing late effects "can help to identify possible interventions, including pharmacologic and behavioral interventions" that may curtail those risks, Dr. Casillas said.

Many survivors of AYA cancers are often unaware of or underestimate their heightened risk for late effects.

Studies that aim to help prevent late effects in AYA survivors or minimize their impact are being launched. At St. Jude, for example, a study is under way to promote the use of telephone quitlines to survivors of pediatric and AYA cancer who smoke.

And at the City of Hope Comprehensive Cancer Center in Duarte, CA, Dr. Melanie Palomares and her colleagues have launched a clinical trial to determine whether treatment with low-dose tamoxifen can reduce the risk of breast cancer in female survivors of pediatric and AYA Hodgkin lymphoma.  

These women are at increased risk of breast cancer because of the radiation treatments they received to the torso area, according to Dr. Smita Bhatia, director of the Center for Cancer Survivorship at City of Hope and COG associate chair.

Awareness and Monitoring are Critical

Diagnosed at age 18 with Burkitt lymphoma, Joe Schneider recalls the short but grueling high-dose chemotherapy treatment he received as part of a clinical trial at the NIH Clinical Center. The vomiting, fatigue, and other effects of the chemotherapy were far worse than he had anticipated. "If this comes back, there is no way in hell I'm going to go through treatment again," Schneider, now 35, remembers thinking.

After surgery for a small, localized recurrence and 3 years of monitoring, his time in the cancer system, so to speak, was completed.

"They were like, 'Now you're on your own,'" he said. "I didn't really know what that meant."

Schneider's experience of more than a decade ago is not uncommon today, Dr. Casillas acknowledged. "Many survivors of AYA cancers are not receiving risk-based, long-term follow-up care when they transition from completion of active treatment to the survivorship phase of care," she said.

Depending on the type of chemotherapy regimen they received, for example, many AYAs should be routinely monitored for cardiovascular problems like high blood pressure and congestive heart failure, she explained.

The approach to monitoring and surveillance for late effects should be tailored to the types of treatments survivors received, Dr. Bhatia stressed. "For the vast majority of late effects, there is a very clear relationship with specific chemotherapeutic agents and radiation exposures," Dr. Bhatia said, such as the breast cancer risk in female Hodgkin lymphoma survivors.

Schneider, an active member of the cancer advocacy community, learned enough in his interactions with other survivors to realize that he needed to monitor his health more carefully. He enrolled in a long-term care program for pediatric cancer survivors and some AYA cancer survivors, called STAR, at Northwestern University's Lurie Comprehensive Cancer Center.

It wasn't until he enrolled in STAR, Schneider said, that he realized the high doses of the chemotherapy drug methotrexate that had been part of his cancer treatment could have a deleterious long-term impact on his bones.

Many survivors of AYA cancers are not receiving risk-based, long-term follow-up care when they transition from completion of active treatment to the survivorship phase of care.

—Dr. Jackie Casillas

Now in its tenth year, the STAR program offers comprehensive long-term care specifically for adult survivors of childhood cancers. STAR only accepts survivors who were diagnosed with cancer at age 21 or younger, explained Karen Kinahan, the program's clinical nurse specialist.

Approximately two-thirds of the STAR participants were treated at Children's Memorial Hospital in Chicago, which offers a pediatric version of the STAR program, said Kinahan, who works closely with the Northwestern program's medical director, Dr. Aarati Didwania, a general internal medicine physician, and Dr. Lynne Wagner, the adult program's clinical psychologist.

Survivors who enroll in STAR are seen at least annually and treated or directed to the appropriate specialists according to the COG clinical guidelines, Kinahan said. The program also includes a research component to assess outcomes such as quality of life and treatment effects, as well as an education component for survivors and their families about late-effect and long-term care issues.

"When many of the relatively older survivors, who have been dealing with their health problems on their own, find our program, they are really grateful," Kinahan stressed. "Many will say, 'I've been looking for something like this my whole life.'"

Learning from History

Another initiative to improve the long-term care and quality of life of pediatric and adolescent survivors is the Passport for Care (PFC) program. Spearheaded at Texas Children's Cancer Center and the Baylor College of Medicine, the PFC is an Internet-based tool that provides a detailed summary of a childhood or adolescent survivor's cancer treatment history. This information is then plugged into an algorithm that generates tailored recommendations for monitoring and managing that individual's health, based on the COG guidelines.

"It provides all of the information that the survivor needs to know [and] what they need to guide their care through the rest of their lives," explained Dr. David Poplack, director of Texas Children's Cancer Center, who co-developed the PFC program with Dr. Marc Horowitz, also of Texas Children's Cancer Center. "Most importantly, it provides an opportunity to share that information with their physician. In effect, it makes any physician a cancer survivorship expert."

National rollout has already begun, with over 20 institutions currently using the PFC. The tool is also now available to all COG institutions, and within the next year most COG sites expect to be using it, Dr. Poplack said. A "survivor portal" that will include tailored follow-up guidelines and information, and an array of social media tools, is nearly finished.

The PFC addresses the needs of AYA survivors who were diagnosed with pediatric and adolescent cancers prior to age 21. As clinical guidelines are developed for survivors of cancers that affect young adults in the older age range of the AYA population, they will likely be rolled into the PFC, Dr. Poplack said.

Carmen Phillips

Addressing Fertility Concerns for AYA Cancer Patients

Cancer treatments such as certain types of chemotherapy and radiation can pose a threat to fertility for both male and female AYAs with cancer. Although most young people will not be rendered infertile as a result of treatment, potential effects on fertility can be psychologically devastating, particularly if the effects are not acknowledged or addressed.

Indeed, the Science Task Force of the LIVESTRONG Young Adult Alliance recently identified issues regarding future fertility for AYA cancer patients as a high-priority research question for this population.

In particular, the task force focused on "the communication that does or doesn't go on between health care providers, primarily oncologists, and patients about fertility risks of cancer therapy and the opportunities for fertility preservation," said task force member Dr. Brad Zebrack of the University of Michigan. Those conversations should occur early on so that AYA patients can make informed decisions, yet physicians often do not initiate them.

In the clinic, researchers are testing strategies for preserving fertility for patients undergoing cancer treatment. Results of a randomized clinical trial published July 20 in JAMA showed that premenopausal women with early-stage breast cancer who took the synthetic gonadotropin-releasing hormone drug triptorelin during chemotherapy had lower rates of chemotherapy-induced early menopause than those who did not take the drug.

Twelve months after completing chemotherapy, the rate of early menopause was 25.9 percent among the 133 women in the chemotherapy-alone group and 8.9 percent among the 148 women in the chemotherapy plus triptorelin group.

For more information on fertility risk and fertility preservation for patients undergoing cancer therapy, read "Preserving Fertility While Battling Cancer" and watch the video, Cancer Research Now: Fertility Issues for Adolescents and Young Adults with Cancer

Elia Ben-Ari

Special Issue: Adolescents and Young Adult Cancer

AYAs Are Not Alone: Confronting Psychosocial Challenges of Cancer

High ropes course (Photo courtesy of Teen Impact) Teen Impact, a support program based at Children's Hospital Los Angeles, organizes annual 3-day psychosocial retreats that include a high-ropes course. Such activities help build self confidence, self esteem, and trust among peer group members. (Photo courtesy of Teen Impact)

When Huong Do was 23 years old and less than a year out of college, she found herself face-to-face with a medical diagnosis that few of her peers could understand or would ever have to confront: an aggressive large B-cell lymphoma. "The biggest thing at the beginning was that whenever I told somebody that I had cancer they treated it as a tragedy…and that made me very sad," said Do, now 34 and a biostatistician in New York. She found help at a weekly cancer support group run by Gilda's Club, now part of the Cancer Support Community.

"The thing about being with other people who have cancer is that this is life for all of us, so you find the humor in situations and can joke about things," Do explained. "And that made it more normal and let me move past feeling like it was a tragedy."

The desire for a sense of normalcy in the face of illness is typical of adolescents and young adults (AYAs) affected by cancer, who face myriad psychosocial challenges ranging from emotional to financial. These challenges occur in the context of a critical period in human development, when young people are becoming more independent, establishing relationships and careers, exploring their sexuality, and forming their own worldview.

Spurred by AYA cancer patients and survivors, health care providers have recently begun to recognize that AYA patients have unique and specific psychosocial needs. Getting support to meet those needs is critical for enabling AYAs to adapt and cope as they navigate the course of their illness and beyond.

And that support can come in many forms, from formal support groups to social events and adventure retreats that bring together AYA cancer patients and survivors.

Many Forms of Isolation

"When you're diagnosed with cancer, it really isolates you from your peers who are out there getting jobs, starting families," said Dr. Brad Zebrack of the University of Michigan School of Social Work, who is himself a Hodgkin lymphoma survivor.

Feeling alone and lonely is common for AYA cancer patients and survivors, and this isolation can be physical as well as emotional. Because cancer is relatively rare in teens and young adults, they may encounter few if any other patients their age in hospitals and doctor's offices. Moreover, treatment may require hospitalization, sometimes far from home.

Emotional isolation can result from being unable to hang out with one's friends and missing school, work, and important social events such as school dances and graduations. A desire for normalcy may keep AYAs from sharing their cancer experience with their healthy peers, adding to the sense of isolation. And AYAs with cancer often undergo physical changes such as hair loss or even amputations that make them feel different from their peers.

Furthermore, the experience of having cancer may change young people in ways that make it difficult to relate to their friends without cancer.

"These young people witness events that others their age don't necessarily experience, such as illness, suffering, and death," said Dr. Lori Wiener, who heads the Psychosocial Support and Research Program in NCI's Pediatric Oncology Branch and works with AYA patients and survivors. "They grow in ways that their peers don't, and they may develop tremendous wisdom and a new perspective of what's important and what isn't," she said. Fear of one's own death can also contribute to feeling emotionally isolated.

All of this can add up to significant psychological distress. "Compared to older adults with cancer, young adults are more likely to be distressed and experience symptoms of depression and anxiety," said Dr. Zebrack. Such symptoms can be linked to being diagnosed with cancer at a time of life when many people feel invincible. "There's a likelihood that a 25-year-old has never even been to a funeral, let alone dealt with a life-threatening disease," he said.

Together, the emotional distress and isolation faced by AYAs may interfere with the development of their identity and sense of self, contribute to poor treatment adherence, and lead to other problems down the road.

Finding Help and Support

Lauren Sidorowicz (Photo by Diane Baker) Lauren Sidorowicz, age 26, is a long-time patient in NCI's Pediatric Oncology Branch, which follows patients through childhood, adolescence, and young adulthood and provides them and their families with psychosocial support services. (Photo by Diane Baker)

One key ingredient of effective support for AYAs is connecting with others who share the cancer experience. "The biggest part of finding people who have gone through the same experience as you is that you want to know that you're not alone, and it's not just you who's having a hard time with things and learning how to cope," said Do. Allowing AYA patients to continue living as normal a life as possible is also critical.

Growing awareness of the importance of age-appropriate psychosocial support, along with the advent of the Web, smart phones, and social media, have increased the number and variety of resources available for AYAs affected by cancer. These resources can provide an antidote to feelings of isolation and loneliness and help restore a sense of normalcy.

Some organizations provide financial help, career guidance, and other tangible support for AYA patients and survivors.

And, said Dr. Zebrack, who serves on the steering committee of the LIVESTRONG Young Adult Alliance, "A lot of these resources are being developed by young adults with cancer for young adults with cancer."

One such resource is the I'm Too Young for This! Cancer Foundation (i[2]y), founded in 2007 by Matthew Zachary, who was diagnosed with brain cancer during his senior year of college in 1995. "Back then, there were very few [psychosocial] resources for anybody, let alone a young adult," said Zachary. i[2]y takes an edgy, no-holds-barred approach to cancer support, with its annual OMG! Cancer Summit; the Stupid Cancer Show, a weekly online radio program; and local social events held around the country, including meetups, tweetups, boot camps, and barbecues.

"We build communities by way of giving these young adults what they've never had before," Zachary said. "You get to meet young adult survivors in a nonthreatening, nonclinical environment" at events that restore dignity, help AYAs feel normal, and empower survivors, he said. Zachary also sees i[2]y as an "event-marketing and PR umbrella for the entire [AYA cancer] movement," helping to connect patients and survivors with service organizations like Camp Mak-A-Dream and First Descents.

Other support organizations founded by AYA cancer survivors include Planet Cancer, one of the first online communities for young adults with cancer; Vital Options International; LIVESTRONG; and the Ulman Cancer Fund for Young Adults. (For links to more organizations, see NCI's AYA cancer Web portal.)

One of the earliest support programs created specifically for teens with cancer in the United States is Teen Impact, which was founded in 1988 by Dr. Aura Kuperberg and several colleagues at Children's Hospital Los Angeles. Dr. Kuperberg recognized the need for such a program while working with parents of young people with cancer and seeing firsthand the special needs of adolescents.

"The general goal is to help young people cope and adjust, but we do it through the power of peer support," with guidance from psychologists and social workers, Dr. Kuperberg said. "We provide 'clinical social therapy,' a unique model that combines therapy in a social package" in the form of 3-day retreats, dances, and other informal get-togethers that include formal discussion groups where young people can share their true feelings and "tell their story and not be judged or feel pitied," she said.

Teen Impact now serves preteens and young adults as well as teens and offers support groups for parents and siblings of patients.

Seeking Balance

OMG! Cancer Summit group photo (Photo courtesy of i[2]y) The I'm Too Young for This! Cancer Foundation (i[2]y), known for its edgy approach to cancer support for young adults, holds an annual OMG! Cancer Summit. (Photo courtesy of i[2]y.)

As more face-to-face and online support options become available for AYAs affected by cancer, it's important to recognize that one size does not fit all. "Like any psychosocial intervention for any cancer patient, the goal is targeted interventions," Dr. Zebrack said. "We need the research to know which interventions, or which support programs, are most relevant and most appropriate for which AYA subgroups."

In the meantime, Dr. Kuperberg said, "the increasing number of survivors, including survivors of childhood cancers who grow into adolescence and young adulthood, has created a demand for new and innovative programs that meet their specific needs."

But total immersion in the world of cancer support can be unhealthy, Dr. Wiener said. Her previous research with young people living with HIV showed that "those who are able to balance a life spent with people who really understand what they're going through with a life of 'normalcy' are the ones who do the best," and she believes the same applies to AYAs affected by cancer. These days, she noted, technologies such as texting and videoconferencing help AYA patients keep in touch regularly with friends and even continue their schooling.

Dr. Zebrack advises AYAs to "get tips from others who've been through what you're going through," and "use what seems to work for you and jettison what doesn't seem to be helpful." A major point, he said, is to "figure out how you can get involved in your own care, to not be a victim and just let things happen to you."

Helping other AYAs newly diagnosed with cancer also is empowering and helps young people adjust psychologically.

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

Video produced and edited by Sarah Curry

Room for Improvement

Physicians and nurses must also play a role in helping their AYA cancer patients cope with their illness. Indeed, Dr. Zebrack said, "There needs to be a little bit more understanding of theories of human development as they apply to teens and young adults."

For instance, providers should let AYA patients get involved in their own care and decision making, should not condescend when talking with these patients, and should be open and frank in addressing patient concerns such as fertility preservation and sexuality. Adjusting treatment schedules and appointment times to enable AYA patients to attend important social events is also helpful.

Zachary, too, sees room for improvement among providers. For that reason, he said, i[2]y "often targets young nurses, young social workers, young oncologists, residents, and fellows through our outreach, to let them know that this is about their generation."

"Training pertaining to the developmental needs of adolescents and young adults is still in its infancy and requires a lot of attention and research," Dr. Wiener said. "But the need for it has been recognized and heard."

Elia Ben-Ari

Forging Ahead with Psychosocial Research for AYAs

When it comes to research on psychosocial issues that affect AYA cancer patients and survivors, "we have done some important descriptive work in the past, and much more of that needs to continue. But more and more there's [also] intervention work going on," said Dr. Pamela Hinds, who directs the Department of Nursing Research and Quality Outcomes at Children's National Medical Center in Washington, DC.

One issue that Dr. Hinds and her colleagues are studying is fatigue and altered sleep during cancer treatment and survivorship. "Fatigue is almost a universal experience, and it can linger from the point of diagnosis for up to 15 years after treatment ends," said Dr. Hinds. "If a child or adolescent is fatigued to a high level, they are not able to participate in developmentally important activities such as socializing," she noted.

She and her colleagues found that physical activity can help fight fatigue in adolescents who are hospitalized for cancer therapy. They are also testing other interventions, such as ways to filter light and noise from patients' rooms.

In an ongoing study funded by the nonprofit HopeLab Foundation, Dr. Brad Zebrack of the University of Michigan and his colleagues have been following teens and young adults, ages 14 to 39, over a 2-year period. The researchers are assessing the teens' use of psychosocial support services while measuring their levels of distress and quality of life at four intervals over the course of the study, to see if there is any association between changes in distress levels and use of support services.

Meanwhile, in NCI's Pediatric Oncology Branch, Dr. Lori Wiener is developing an advanced care planning guide for AYA cancer patients who are facing the possibility of a terminal illness. She and her colleagues are also conducting an inpatient study aimed at "trying to take the isolation out of medically required isolation." (Patients often have to be medically isolated when they have an infection or when the risk of infection is high.) "We're trying to better understand the process and to develop interventions that can increase understanding and reduce loneliness, anxiety, and emotional isolation," Dr. Wiener explained.

In another effort to reduce isolation among hospitalized AYA cancer patients, Dr. Aura Kuperberg at Children's Hospital Los Angeles recently received a grant to enable live webcasting of Teen Impact's group sessions to patients who are confined to their hospital rooms. "Teens will be able to view the sessions from their computers and interact with members of the live group while lying in their hospital beds," said Dr. Kuperberg, who led a pilot project on a similar approach and plans to study the new program's effectiveness.

"This is a very exciting time for psychosocial interventions that are new and being studied, and interventions that are being incorporated into clinical practice," concluded Dr. Hinds.

Elia Ben-Ari

A Conversation With

A Conversation with Matthew Zachary: The Young Adult Cancer Movement

Matthew Zachary Matthew Zachary

In 1995, during his senior year of college, aspiring concert pianist Matthew Zachary was diagnosed with brain cancer and entered a cancer world geared toward the needs of children and older adults. A decade after emerging from the experience, he founded the I'm Too Young For This! Cancer Foundation (i[2]y), which serves as a "community of support" for young adults, survivors of childhood cancers, and caregivers. Through its Web site, cancer conferences, forums, and Stupid Cancer Radio Show, i[2]y has become one of the many voices championing the needs of young adults with cancer.

Why did you found the I'm Too Young For This! Cancer Foundation?

I founded i[2]y because I'm a young adult cancer survivor, and I did not want anyone to have to go through what I went through. I was diagnosed with brain cancer in 1995 when I was in college. So I went through all the same stuff that young adults experience—the isolation, the fear, the misunderstanding, the stigma, the "I'm just getting my life started, how could this happen to me? I'm not 80 years old."

What sets your organization apart?

We are a grassroots organization that's now evolving into a mainstream programmatic organization. We have paid attention to the fact that cancer is an extremely different type of experience when it happens to young adults. Before the young adult cancer movement, everyone thought about cancer in terms of little kids and everyone else. We've broken through that assumption. And, thanks to advances in research, there are now clinical and population studies to support the view that people between the ages of 18 and 40 are the most underserved age group in cancer.

We want young adults with cancer to be aware of all the resources that can help them get busy living. Our Web site serves as a portal for other young adult organizations that provide direct patient services specifically for this age group. People can discover these organizations because they visit our site, hear us speak, or listen to the radio show. We introduce them to an entire world they might otherwise not have known about.

What makes young adults with cancer unique?

For starters, we're not little kids and we're not older adults. We don't necessarily want to journal about our feelings or go to a support group. We want to go online, or go to a bar, or just feel like we're living our lives with people who [understand what we're going through]. The young-adult cancer movement was born out of sheer necessity.

What kind of feedback do you get?

We have scores of testimonials from people who have attended our events or just learned that we exist. One person said, "My doctor may have cured my cancer, but learning about your community has saved my life." A woman who attended our annual conference this year said, "I learned to keep fighting, to be my own advocate, and to never give up, no matter what the doctor says." She learned that by coming to the event.

It's incredibly powerful for a young adult with cancer to discover an entire community dedicated to their age group—people who are not their moms, not their grandmas, and who get it.

How does your group interact with doctors?

We recently received our first CME (Continuing Medical Education) certification, so we can now train and educate doctors on things like best practices, standards of care, patient communication, and patients' rights. The doctors who are in their 20s and 30s—the fellows—are the same age as the people we serve. These doctors come to our conferences simply because they want to understand what it's like to have cancer at their age. [That understanding] helps them become better providers.

Do you encounter doctors who are cancer survivors?

They are few and far between, but they're out there. I can tell you that a significant percentage of young adults who get cancer change their entire career track because they then want to go into medicine. We're looking at a whole new group of medical professionals [who will emerge] in the next 10 years who have had cancer and want to give back. This is a sad blessing.

How old are you, and do you plan to continue your outreach efforts to other AYAs in the future?

I'm 37. I will be aging out of this demographic in about 3 years. But we're developing an alumni network that will carry on the legacy of the movement and build new leadership. As more people join the AYA age group, whether they are long-term childhood cancer survivors or they're people who just get cancer after age 18, they're going to need the alumni.

I look forward to 40, because I'll just be alive. And I can't wait to be an alumnus, an ambassador, a steward.

Are there any times you are able to forget your cancer experience?

Yes. If I'm with my wife and my kids and we're on vacation—and I'm not tied to my phone—I can revel in those moments.

But I've dedicated my whole life to a movement, and it can be hard to escape the world you build for yourself. My father once gave me a great quote: "I wish to have a job I love and never work again." That's my life.

Edward R. Winstead

Cancer Research Highlights

Breast Cancer Cells Found by Immunochemistry in Sentinel Nodes Not Associated with Survival

The detection of breast cancer cells in sentinel lymph nodes by immunochemistry—antibody-based techniques to detect cancer cells—in addition to standard tissue staining does not appear to help predict survival after treatment for breast cancer. These results, from the American College of Surgeons Oncology Group (ACOSOG) Z0010 study, were published online July 26 in JAMA.

ACOSOG researchers from 126 hospitals, led by Dr. Armando Giuliano of the John Wayne Cancer Institute in Santa Monica, CA, enrolled 5,119 women with early-stage breast cancer and identifiable sentinel lymph nodes in the prospective observational study between May 1999 and May 2003.

Most of the women had stage I, estrogen receptor-positive breast cancer. Ninety-one percent received whole-breast radiation, 83 percent received chemotherapy, and 68 percent received hormone therapy.

Standard tissue staining found cancer cells in the sentinel lymph nodes of almost one-quarter of the women. Of the remaining women, 85 percent were assessed using immunohistochemistry (IHC). In about 10 percent of those women, IHC found occult (initially undetected) metastases in the sentinel lymph nodes that standard tissue staining had failed to detect. However, the researchers did not see a statistically significant difference in overall survival between women who did and did not have IHC-detected cancer cells in their lymph nodes.

Using a similar test called immunocytochemistry, the researchers found occult metastases in the bone marrow of 104 (3 percent) of the 3,413 women who had samples that could be tested. The presence of these cancer cells was associated with decreased overall survival. However, when other factors, such as age and tumor size, were included in the analysis, the association between occult bone marrow metastases and overall survival disappeared. The small number of women with positive bone marrow findings may explain this absence of statistical significance, noted the authors.

The researchers also pointed out that most patients in the Z0010 trial received adjuvant systemic therapy, which is standard practice in the United States, independent of immunohistochemical findings. “Thus,” wrote the authors, “although the effect of untreated micrometastases is unknown, it is not relevant to current practice” because occult sentinel lymph node metastases treated with adjuvant systemic therapy do not affect survival.

Because IHC of the sentinel nodes did not help predict survival, and the incidence of occult bone marrow metastases was “too low to recommend incorporating bone marrow aspiration biopsy into routine practice” for patients with early-stage breast cancer, the authors concluded that routine immunochemical examination of sentinel nodes and bone marrow is “not clinically warranted” for these women.

“Many laboratories currently do immunohistochemistry to look for sentinel lymph node metastases, and this study does not support this expensive practice,” agreed Dr. Jo Anne Zujewski, head of Breast Cancer Therapeutics in NCI’s Division of Cancer Treatment and Diagnosis.

Radiation Plus Short-Term Hormone Therapy Improves Survival of Men with Early-Stage Prostate Cancer

In men with intermediate-risk, early stage prostate cancer, short-term treatment to lower male sex hormones given in combination with radiation therapy prolonged overall survival compared with radiation therapy alone, according to an NCI-supported clinical trial. The results of the study were published July 14 in the New England Journal of Medicine.

The trial, which was conducted by the Radiation Therapy Oncology Group (RTOG) at 212 centers in the United States and Canada, enrolled nearly 2,000 patients with localized nonmetastatic prostate cancer and with serum prostate-specific antigen (PSA) levels of less than 20 ng/ml. Patients were randomly assigned to treatment with radiation therapy alone or radiation therapy plus short-term (4 months) androgen deprivation therapy (STADT) using drugs that drastically lowered their natural production of testosterone.

The researchers reported a statistically significant improvement in overall survival after 10 years for participants who received STADT plus radiation compared with those who received radiation therapy alone (62 percent versus 57 percent overall survival).

Men who received radiation therapy plus STADT were also less likely than men who received radiation therapy alone to die of prostate cancer (4 percent versus 8 percent). Benefits of the combined treatment were limited mainly to patients with intermediate-risk disease and were not seen for men with low-risk prostate cancer, the researchers said. (Men with intermediate-risk disease have higher Gleason scores, PSA, and clinical stage values than men with low-risk disease.)

The study included nearly 400 black men, who have a higher prostate cancer risk than white men. Benefits from the addition of STADT were similar in white and black men for 10-year overall survival, prostate cancer-specific mortality, and biochemical failure (i.e., a rise in PSA levels after initially lowered levels due to androgen deprivation therapy).  

“This study has important significance for clinical care,” said lead author Dr. Christopher U. Jones, of Radiological Associates of Sacramento, CA. “We now have strong scientific evidence about which patients with early-stage prostate cancer benefit from STADT” added to conventional radiation therapy. But the authors also note that new radiotherapy techniques now make it possible to use higher doses of radiation than were used in this study. A successor RTOG study will investigate the value of adding STADT in men with intermediate-risk disease treated with these new radiation methods.  

In Hodgkin Lymphoma Study, Side Effects Distinguish Treatments

A clinical trial has shown that two strategies for treating advanced Hodgkin lymphoma are nearly equal in their long-term effectiveness, but one is associated with more severe side effects, including a greater risk of treatment-related deaths, infertility, and second cancers. The findings appeared in the July 21 New England Journal of Medicine.

In the study, researchers in Italy compared outcomes in patients randomly assigned to receive one of two multidrug chemotherapy regimens, known as BEACOPP and ABVD, as well as additional therapy for patients in either group who needed it. (Patients who had residual disease after initial therapy or who had a complete response and then relapsed were treated with high-dose salvage chemotherapy with autologous hematopoietic stem-cell transplantation.)  

Dr. Alessandro Gianni of the Milan Cancer Institute and his colleagues found that the 7-year rate of freedom from first progression was 85 percent with BEACOPP versus 73 percent with ABVD. However, the 7-year survival rate for patients in the BEACOPP group was 89 percent, compared with 84 percent for the ABVD group. The difference was not statistically significant. Thus, after salvage therapy, the overall survival outcomes in the two groups were similar, and the ABVD regimen had a clear advantage in terms of side effects.

In the absence of a survival benefit, “patients should be informed of the trade-off involved in choosing between two initial therapies,” the study authors wrote. They noted that the BEACOPP therapy exposes patients who would have been cured by ABVD (i.e., the majority of patients) to an unnecessarily high risk of severe toxic effects, whereas the use of ABVD means that a small proportion (one of eight in this study) of patients will need high-dose salvage treatment, with its associated severe toxic side effects.

Three-quarters of the patients in the ABVD group who responded to treatment were spared infertility, the risk of leukemia, and other toxic effects of the more intense BEACOPP treatment, noted Dr. Joseph Connors, clinical director of the Center for Lymphoid Cancer at the British Columbia Cancer Agency and author of an accompanying editorial. Many patients with this disease are young adults who will have to live with the toxic side effects of their treatments for the rest of their lives.

“This study shows that you cure just as many people with either strategy,” said Dr. Connors. The findings reaffirm what many clinicians are doing, which is to use ABVD as the primary regimen, he noted.

Nonetheless, Dr. Connors continued, deciding which regimen to use has been an open question for the field, and the new study “clarifies the issue substantially.” The ABVD regimen has been used for several decades, and German researchers developed the more intensive BEACOPP regimen during the 1990s.

The new findings also establish an important principle, Dr. Connors added. “For diseases like this one that can often be cured, the proper way to compare outcomes of treatments is to look at overall management strategy as opposed to simply looking at the outcome of the primary therapy,” he said. “You need to look at the whole package.”

FDA Update

Advisory Panel Recommends Accelerated Approval for Brentuximab

A Food and Drug Administration (FDA) advisory committee has unanimously voted in favor of granting accelerated approval of the drug brentuximab vedotin (Adcetris) for some patients with Hodgkin lymphoma and anaplastic large cell lymphoma (ALCL). The FDA must decide by August 30 whether to grant accelerated approval for brentuximab for these two indications. The agency is not bound by the committee's recommendations.

The FDA's accelerated approval process makes available potentially beneficial therapeutic options for serious diseases with an unmet medical need. Larger confirmatory trials are then required to validate the findings from the earlier trials and transition the drug to a regular approval.

The votes from the FDA's Oncologic Drugs Advisory Committee were based on the results of two single-arm phase II trials that tested brentuximab in patients with Hodgkin lymphoma who had relapsed after an autologous stem cell transplant and in patients with relapsed or refractory ALCL, respectively. In both cases, there are few proven treatments for these patients. Results from the trials were presented in December at the American Society of Hematology annual meeting.

Brentuximab is an antibody-drug conjugate, an antibody that is chemically linked to a drug. The antibody component of brentuximab targets the CD30 protein, which is expressed on the surface of most Hodgkin lymphoma and ALCL cells but very few noncancer cells; the linked drug is the chemotherapy agent MMAE.

In the 102-patient Hodgkin lymphoma trial, three-quarters of patients had substantial tumor shrinkage (objective response) and one-third of patients had their tumors eradicated (complete response). In the 58-patient ALCL trial, 86 percent of patients had an objective response and just over half had a complete response.

Seattle Genetics, which developed brentuximab, had sought a regular approval for the drug. But because "a clear understanding of a risk-to-benefit evaluation may not be optimal from single-arm trials," the FDA recommended that the drug move forward initially under the accelerated approval process, explained Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research.

Despite the unanimous vote in favor of accelerated approval, the FDA and several committee members said that a phase III clinical trial being conducted in patients with Hodgkin lymphoma, called ATHERA, was not properly designed to be an adequate confirmatory trial and that at least one other trial would be necessary to eventually gain regular approval.

"There is no question that this drug works," said ODAC Chair Dr. Wyndham Wilson of NCI's Center for Cancer Research. But, among other concerns, he added that because of the way the ATHERA trial was designed it will probably not identify those who are most likely to benefit from the drug, including those who might be cured by its use.

The FDA and Seattle Genetics, which developed and manufactures brentuximab, will further discuss the appropriate design of confirmatory trials to support regular approval of brentuximab for Hodgkin lymphoma and ALCL, according to an FDA spokesperson.

"We are committed to working with the FDA on the ATHERA trial and other clinical trials as part of a confirmatory study package to support regular approval," said Seattle Genetics CEO Dr. Clay Siegall during a conference call with investment analysts.

Carmen Phillips


NCI Director to Hold Town Hall Meeting

NCI Director Dr. Harold Varmus will host a Town Hall Meeting with staff July 27 at the Lipsett Amphitheater on the NIH campus in Bethesda, MD.

The event is open to the public and can be viewed live starting at 11:00 a.m. ET. An archived videocast of the meeting will be available a few days later.

For a biography of Dr. Varmus as well as other information and video presentations, please visit the NCI Director’s Page.

NCI Translational Science Meeting Sessions to Be Videocast

NCI Translational Science Meeting tile

The NCI Translational Science Meeting 2011: From Molecular Information to Cancer Medicine will be held on July 28 and 29 in Washington, DC. This year's meeting will explore the convergence of molecular information ("omics" technology) and clinical care, with the goal of accelerating early translational cancer research to speed therapeutic benefits to patients.

The meeting is by invitation only, but morning sessions will be videocast live and archived at Sessions that will be videocast include:

Thursday, July 28, 2011, from 8:00 a.m. to 12:30 p.m. ET

  • Opening Plenary Session
  • Galvanizing Examples: Session I
  • Welcome by NCI Director

Friday, July 29, 2011, from 8:00 a.m. to 12:00 noon ET

  • Opening Plenary Session
  • Galvanizing Examples: Session II

For more details on these sessions, please visit the meeting Web site.

Thai Princess Signs Agreement with NCI

H.R.H. Princess Chulabhorn Mahidol and NCI Director Dr. Harold Varmus sign a Natural Products Collaboration Agreement H.R.H. Princess Chulabhorn Mahidol and NCI Director Dr. Harold Varmus (seated) sign a Natural Products Collaboration Agreement, while Khuning Laxanachantom Laohaphan, Dr. Somsak Ruchirawat, and NCI's Dr. David Newman (left to right) look on.

Her Royal Highness Princess Chulabhorn Mahidol of Thailand visited NIH on July 21 and signed a Natural Product Collaboration Agreement with the Developmental Therapeutics Program (DTP) in NCI's Division of Cancer Treatment and Diagnosis.

H.R.H. Princess Chulabhorn, who has a Ph.D. in organic chemistry and has taught courses in natural products chemistry, is the founder and president of the Chulabhorn Research Institute (CRI), whose mission focuses on global collaboration and the application of translational discoveries to improve the quality of life for the people of Thailand.

DTP studies natural products and synthetic compounds to find disease-fighting compounds and is interested in investigating plant, terrestrial, and marine species native to Thailand that may have properties useful for treating cancer.

The agreement formalizes ongoing collaborations and the sharing of knowledge, expertise, and technology between NCI and CRI.

NCI's Early Detection Research Network Wins NASA Award

The National Aeronautics and Space Administration (NASA) has awarded NCI's Early Detection Research Network (EDRN) Informatics Team the NASA Honors Award for Group Achievement for the innovative and pioneering use of NASA data system technologies to promote data and specimen sharing among cancer biomarker researchers. 

The award will be presented to EDRN teams from NASA's Jet Propulsion Laboratory, NCI, Dartmouth, and the EDRN Data Management and Coordinating Center at Fred Hutchinson Cancer Research Center.

Under the leadership of Dr. Sudhir Srivastava, chief of NCI's Cancer Biomarkers Research Group in the Division of Cancer Prevention, the EDRN Informatics Team pioneered and deployed a highly distributed national data system to implement cancer biomarker data analysis and research. This project is a flagship example of successful technology infusion and transfer between agencies.

The informatics platform has enabled EDRN science teams to share and integrate diverse datasets and software platforms for complex biomarker research, including discovery and validation of cancer biomarkers.

Author and Oncologist Siddhartha Mukherjee Speaks at NIH

Pulitzer Prize-winning author Dr. Siddhartha Mukherjee delivered a special lecture titled "Constructing a History of Cancer" at the NIH main campus on June 15. The lecture was based on his book, The Emperor of All Maladies: A Biography of Cancer, which won the 2011 Pulitzer Prize for general nonfiction.

Dr. Mukherjee is an assistant professor in the Division of Hematology/Oncology at the Columbia University Medical Center. His lab focuses on the biology of hematopoiesis and leukemia. He has published a number of articles in Nature, the New England Journal of Medicine, the New York Times, and The New Republic.

View an excerpt of the presentation below, or view the full, hour-long lecture online.

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

Latest Issue of CCR Connections Released

CCR Connections

A new issue of the NCI's Center for Cancer Research (CCR) news magazine, CCR Connections, is available online. 

The latest issue demonstrates that research advances come from tackling difficult questions by means of long-term investment and persistence. CCR-led research advances are highlighted, including a mouse model developed by CCR researchers to study the origins of metastatic prostate cancer and an anticancer target called heat shock protein 90.

Other articles include a look at the role that chromatin plays in gene regulation. This issue also includes a profile of CCR's Dr. Christina Annunziata, who has studied the NFkappaB pathway in several different cancers since she was a graduate student; and summaries of several recent CCR scientific publications and staff awards.

CCR Connections is published semiannually. Please send requests for print or online subscriptions to

Special Issue: Adolescents and Young Adult Cancer

Cancer Research Now: Adolescent and Young Adult Cancers

Cancer researchers, advocates, and a cancer survivor introduce the topic of adolescent and young adult (AYA) cancers. AYAs with cancers have received relatively little attention compared with children and older adults with cancer.

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

Video produced and edited by Sarah Curry