Survival for Youths with Cancers Remains Stagnant

When adolescents and young adults develop cancer, clinicians contend with an entirely different set of considerations in treatment and follow-up, as illustrated in a joint presentation at the 15th Annual National Comprehensive Cancer Network (NCCN) meeting by Peter F. Coccia, MD, UNMC Eppley Cancer Center at the Nebraska Medical Center in Omaha; George D. Demetri, MD, Dana-Farber Cancer Institute, Boston, Massachusetts; and Nita Seibel, MD, National Cancer Institute, Bethesda, Maryland. In this “Overview of Adolescent/Young Adult (AYA) Oncology,” the speakers discussed the incidence of cancer in the AYA population, the most prevalent malignancies, and the challenges in treating these patients.

For purposes of the presentation, Coccia defined AYA patients as those aged 15 to 29 years. The overall rate of cancer, said Coccia, is low in children, with less than 1% of cases occurring in individuals aged <15 years and 2% in AYAs. Cancers more common in children include acute leukemia, lymphomas, neuroblastoma, and brain tumors. In patients aged 15 to 19 years, you begin to see cases of testicular and female genital tract cancer, and in those aged 20 to 29 years, the trend is toward more adult cancers. “The notion that childhood and adolescent cancer is primarily liquid malignancies and sarcomas holds very true,” Coccia said.

Unlike survival rates for adult and pediatric patients, which have improved in the past 20 years for many cancers, survival rates for AYA patients have largely stagnated, he said. Reasons for this include lack of clinical trial participation, biological differences in patients and in the disease, fewer resources, lack of healthcare coverage, and inconsistency in treatment by pediatric and adult oncologists. While less than 10% of cancer deaths occur in patients aged <25 years, thinking of it in terms of years of life affected, lost, or potentially gained shows how important it is to treat cancer effectively in this population, Coccia said.

Seibel said participation in clinical trials correlates directly with survival rates. More than 90% of children aged <15 years receive treatment at centers that participate in Children’s Oncology Group trials. Conversely, patients aged 20 to 29 years are most likely to receive care from a private practice, where different physicians take different approaches to therapy. Clinicians need to do more to refer the AYA population to clinical trials or a cancer center with multidisciplinary teams and more specialized services.

Seibel explained that pediatric oncologists have more experience than medical oncologists who see adults in treating acute lymphoblastic leukemia (ALL) and follow strict therapeutic protocols. She pointed to several studies in the United States and internationally that demonstrated patients in the AYA group with newly diagnosed ALL have better outcomes with a more intensive pediatric regimen and extended maintenance therapy. This is also true of patients with bone and soft-tissue sarcoma. Better outcomes with pediatric regimens might be explained by differences in the genetic composition of cancers in adult and pediatric populations.

Some of these biological differences might also contribute to the worse outcomes typically seen in AYA patients. Demetri, an expert in sarcoma, explained that “pediatric gastrointestinal tumor [GIST] is a totally different disease than adult GIST” and does not respond as well to drugs like imatinib, used to treat adult GIST. According to Demetri, a disproportionate number of younger patients have GIST with no KIT or PDGFRA mutations, which imatinib targets. “Memorial Sloan-Kettering Cancer Center started to tease this apart to see if there is a difference between wild type GIST in pediatric and adult patients…there are very big biological differences going on even though there’s no difference in mutation status,” Demetri said.

More research is needed to identify how cancers in AYA patients differ from cancers in the adult and pediatric populations. Demetri said, “I feel strongly that better understanding of the tumor biology is needed.” In addition, Demetri and Seibel agreed that investigators need to look at whether hormonal and pubertal changes affect disease progression and pharmacokinetics. “It’s not simply a matter of puberty,” Demetri noted. “Raging hormones could change things, but it’s not going to be as simple as that.”

Questions investigators need to answer include how kinase inhibitors affect plasma levels in the pediatric world, whether disease distribution might account for some of the disparity in outcomes, and how living alone affects treatment compliance for AYA patients. “Whether patients are emancipated adolescents or still under parental supervision can have a huge impact, particularly in compliance with oral medications,” said Seibel. She said they also need to look at cytogenetic markers and how they relate to prognosis in the AYA contingent.

All the presenters agreed that resolving these questions will require increasing AYA participation in clinical trials. Demetri also emphasized the importance of collaboration between investigators in different parts of the nation and the world to better understand how different cancers affect the pediatric and AYA populations. He explained that this is already being done with the NIH Pediatric and Wild-type GIST clinic, which includes “some of the biggest centers here and abroad, to track a very rare subset of a very rare disease in a very useful way.”