Compared with advances achieved for younger children over the past 30 years, there has been a relative lack of progress in identifying more effective treatments for adolescent and young adult (AYA) cancer patients. Cancer survival rates for AYA patients, who are those diagnosed with cancer at ages 15 through 39, have seen little or no improvement for decades. This concern led NCI and the Lance Armstrong Foundation (LAF) in 2005-2006 to convene a Progress Review Group (PRG) to evaluate the issues behind this bleak trend.
Now a trans-NCI study of AYA patients, led by the Division of Cancer Control and Population Sciences, is under way in seven SEER registries with support from the LAF. The study will investigate patterns of care and outcomes for patients aged 15-39 with acute lymphoblastic leukemia (ALL), lymphoma, sarcoma, and germ cell cancers through a patient survey and medical record examination. The study will assess treatment, physician and facility characteristics, clinical trials participation, barriers to care, as well as the impact of cancer on physical symptoms, psychosocial experiences, financial issues, and quality of life.
Dr. Malcolm Smith of NCI's Cancer Therapy Evaluation Program also points to clinical trials for AYA patients with ALL. "Recent publications have reported that adolescents and young adults treated on pediatric clinical trials have had better outcomes than similarly aged AYA patients treated using adult protocols for ALL," he noted.
One of the trials cited by Dr. Smith is being conducted by the Dana-Farber Cancer Institute (DFCI) Consortium, which presented preliminary findings at the American Society of Hematology annual meeting last year. Current chemotherapy regimens in children with ALL produce event-free survival (EFS) rates of greater than 80 percent compared with EFS rates of 30-40 percent in adults with ALL. DFCI Consortium researchers reported that for patients aged 18-50 with ALL who were treated with an intensive pediatric regimen, the estimated 2-year EFS was 72.5 percent. Although the study requires longer follow up, the preliminary results suggest that intensive treatment strategies for young adults with ALL could represent a major therapeutic advance.
Another study to improve outcomes for young adults with ALL, CALGB-10403, is under way with the NCI-sponsored adult cooperative groups. The study adopts the treatment approach for ALL that is used by the Children's Oncology Group (COG). A retrospective analysis conducted as part of the trial compared outcomes of ALL patients aged 16-20 who were treated by either the CALGB Intergroup physicians or by pediatric COG specialists.
"What we found was that there was tremendous disparity in outcomes and that those AYA patients who were treated on pediatric regimens had significantly improved disease-free survival and overall survival," said Dr. Wendy Stock, associate professor at the University of Chicago Department of Medicine. "It was almost a 30 percentage point difference. That was very disappointing and it stimulated a lot of questions about why this might be."
The Intergroup retrospective analysis, which will be published in Blood, found key differences in both the dose intensity of the drugs used and in the treatment schedules adopted by pediatric versus adult cancer specialists. "In addition to differences in the protocol design and schedule, the outcome disparity also raises questions about protocol compliance and whether adult medical oncologists and the patients that they treat adhere to protocols as rigorously as the pediatric oncologists and their patients," Dr. Stock noted. "We hope to begin to gather specific data about treatment compliance in addition to exploring the feasibility of using this approach to improve outcomes of AYAs with ALL in the adult cooperative groups."