For example, the biology of AML is known to change with age, Dr. Dwyer and her colleagues said, explaining that a recent European study showed that in 5,564 patients with de novo AML, the frequency of favorable cytogenetics was low in infants, increased in children and young adults, and decreased again in middle age and older age (Cancer. 2016 Dec 15;122[24]:3821-30).
“Normal karyotype increases in prevalence from 13.7% in infants to approximately 25% in children, 44% in AYAs, and 50% in adults. Most unfavorable cytogenetic abnormalities are rare across all age groups, though complex cytogenetics are relatively more frequent in infants, decrease in frequency in AYAs, and then increase in frequency beyond AYA,” Dr. Dwyer and her colleagues wrote, noting that it also is becoming more apparent that age influences the presence of AML-related molecular abnormalities.
The authors argue that recognition of age-related differences in disease biology “will provide the best opportunity to improve the clinical outcomes that have been static for decades.”
Dr. Boissel and Dr. Baruchel also note that the “black hole” of understanding of ALL biology in AYAs that characterized the last 15 years has been “nearly brought to light and revealed a continuum between childhood and adult ALL.”
One example of this involves data from the NOPHO-ALL-2008 trial, showing that the proportion of patients with intrachromosomal amplification of the long arm of chromosome 21 (iAMP21), which is a rare event occurring in about 2% of children with ALL, is more frequent in older children and adolescents and is associated with higher relapse risk that is only partially diminished by intensified treatment.
In NOPHO-2008, iAMP21 occurred in 1.5% of patients aged 1-9 years, 5.8% of those aged 10-17 years, and 12% of those aged 17-45 years. The authors provided numerous other examples of such age-related differences in disease biology and concluded that “risk stratification based on recent biology findings and sequential [minimum residual disease] evaluations should now be implemented, as well as new therapeutic options including immunotherapy and targeted therapies, at best within the setting of integrated pediatric and AYA protocols.”
Psychosocial factors
The “financial toxicity” mentioned by Dr. Hanna – the high cost of care, lost work time, and delays in reaching educational and career goals, for example – is a major factor that must be addressed in this population, but there are also many others.
“Cancer is a non-normative event for AYAs. It is extremely disruptive to them physically, psychologically, and vocationally ... and this poses significant challenges,” John M. Salsman, PhD, director of clinical research in AYA oncology at Wake Forest University, Winston-Salem, N.C., said in an interview.
These patients not only have 5-year survival rates that haven’t improved in tandem with those in pediatric and adult populations over the last 3 decades, but in addition to the financial toxicity and strain, they also have higher rates of depression and anxiety, including fear of recurrence, he added.
Courtesy Wake Forest University
Dr. John M. Salsman
“Quality of life is incredibly important, and these things need to be addressed because of the developmental changes AYAs are navigating; there are issues of positive body image, family and career decisions ... These are challenging for anyone, and when you throw a cancer diagnosis into the mix they become disproportionately so,” he said.
In a 2014 study, he and his colleagues found that AYAs with cancer had poorer physical and emotional quality of life when compared with matched controls, but better social quality of life. The latter finding was surprising, and highlights the “critical importance” of the social dimension in AYAs’ lives.
“Patient after patient will say ‘I found out who my real friends are,’ ” Dr. Salsman said. “There’s this refinement and deepening of the social network among some posttreatment survivors.”
Dr. Salsman and his colleagues are using those findings to develop interventions that can maximize self care in posttreatment survivorship – a time when AYAs may feel they have a new lease on life and may be more motivated to adhere to recommendations and take care of themselves.
A randomized controlled pilot study incorporating social media apps and other technologies to build on the positive social components of their lives in promoting physical activity interventions, for example, is underway.
Another intervention targets emotional well-being via web-based tools to increase positive affect. A proof-of-concept study showed that the approach is feasible and well received, and efforts are underway to plan a larger-scale randomized controlled trial, he said.
Dr. Salsman also praised the PRISM (Promoting Resilience in Stress Management) tool developed by researchers at Seattle Children’s Hospital.
PRISM was created to help AYAs with cancer and other illnesses learn coping skills to manage stress after their diagnosis, and to boost quality of life beyond treatment. A digital app has also been developed to be used in conjunction with the program.