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

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