AYA CANCER BIOLOGY AND TRENDS

Publication Details

Adolescents and young adults are more susceptible to certain types of cancers, including leukemia, lymphoma, melanoma, and cancers of the central nervous system, germ cells, connective tissue, and thyroid. This group of cancers differs from the cancers that commonly afflict children or older adults. Consequently, “pediatric oncologists and adult-treating physicians and medical oncologists are not as familiar with this group of cancers as they are with the other cancers that affect their patients,” said Archie Bleyer, clinical research professor at the Knight Cancer Institute of the Oregon Health & Science University (OHSU) (see Figure 1). Brandon Hayes-Lattin, associate professor of medicine, hematology, and medical oncology and the medical director of the Adolescent and Young Adult Oncology Program at OHSU Knight Cancer Institute, said that AYAs are also more likely to be diagnosed with different subtypes of cancers than other groups, which affects what treatments are most likely to be effective for them. For example, one study found that AYAs are more likely to be diagnosed with melanomas that have BRAF2 mutations and thus are more likely to respond to BRAF inhibitor drugs (Menzies et al., 2012). Similarly, AYAs diagnosed with acute lymphoblastic leukemia (ALL) tend to have genetic defects in their tumors that are associated with better prognosis. “This might explain why younger people, even if given the same therapy [as older adults] tend to do better,” he said. However, he also presented data showing that AYA patients who received a pediatric treatment regimen for ALL had a 63 percent event-free survival at 7 years versus 34 percent with the adult treatment regimen (Stock et al., 2008). He added that a recent meta analysis found that patients under the age of 35 with a matched sibling had significantly better survival with an allogeneic bone marrow transplant (Gupta et al., 2013).

FIGURE 1. (A) Relative frequency of the common types of cancers in adolescents and young adults, aged 15–39, 1992–2002, and (B) the prevalence of cancer histology by age.

FIGURE 1

(A) Relative frequency of the common types of cancers in adolescents and young adults, aged 15–39, 1992–2002, and (B) the prevalence of cancer histology by age. The cancers that peak in incidence within each age range are listed in each triangle. (more...)

BOX 1Suggestions Made by Individual Workshop Participants

Address the care needs of Adolescent and Young Adult (AYA) patients diagnosed with cancer

  • Provide a clearinghouse for programs focused on AYA patients with cancer
  • Implement care models that promote timely referral, timely initiation of treatment, and attention to treatment-protocol adherence
  • Establish multidisciplinary care teams with training in the unique needs and developmental stages of AYA patients
  • Integrate information about palliative care into new patient orientation packets and programs and incorporate proactive palliative care across the cancer care continuum
  • Discuss fertility at the time of diagnosis and have in place an established referral mechanism for fertility preservation
  • Design stress-management programs for cancer patients
  • Design lifestyle intervention programs to match the developmental stage and interests of AYA patients
  • Provide guidance on how to maintain effective access to health care and insurance, including follow-up cancer care, survivorship care, and routine primary care

Improve cancer survivorship care for AYA patients

  • Develop new models for transitioning AYAs into survivorship care and provide tiered care to AYA cancer survivors based on their particular long-term risks and psychosocial needs
  • Develop evidence-based guidelines for surveillance of cancer recurrence and screening for new cancers
  • Use an exposure-based approach to risk-reduction strategies for late effects and secondary cancers among AYA cancer survivors
  • Increase efforts to identify patients with genetic syndromes that predispose AYAs to cancer and to implement evidence-based risk-reduction strategies for those patients
  • Foster more collaboration between oncologists and primary care providers
  • Consider fertility preservation post treatment if desired

Improve training, education, and research

  • Provide more specialty training programs and fellowships and continuing medical education programs focused on the care of AYA patients and establish standards for training
  • Address research gaps in psychosocial care, late treatment effects, fertility, lifestyle interventions, access to care, and socioeconomic consequences of cancer diagnosis (such as education, employment, and career)
  • Measure patient outcomes following psychosocial care to ensure that care is informed by evidence
  • Foster more collaboration among various organizations, institutions, and federal agencies
  • Educate the AYA population about new options to obtain and maintain health insurance through the Affordable Care Act (ACA)
  • Use existing data to better understand the patterns of health care utilization and unique burdens of AYA cancer survivors, particularly in relation to the impact of the ACA
  • Develop and leverage online resources to communicate with AYA patients and to facilitate research
  • Tailor communications about research for the AYA population

Bleyer noted that the incidence of melanoma, cervical cancer, and lung cancer has declined among AYAs during the past 10 years, probably due to prevention efforts, including anti-smoking and pro-sunscreen campaigns, restrictions on indoor tanning devices, and use of human papillomavirus (HPV) vaccines. Bleyer said that although the incidence of most of the cancers that AYAs are prone to develop has declined or has not increased in the past 10 years, some types of cancer have become more common in this age group, including kidney, thyroid, breast, colorectal, and testicular cancer and ALL. He said that the increase in colorectal cancer incidence might be due to an increase in HPV-associated rectal cancer combined with an increased likelihood of detection now that colonoscopies are being applied more widely.

He added that although the incidence of both kidney and thyroid cancer has substantially increased among AYAs, this is likely due to increased detection by ultrasound and other diagnostic imaging. “Both are examples of overdiagnosis in which our diagnostic testing has become so advanced and widely available that we are now detecting indolent lesions of epithelial origin (IDLE) that do not need to be fixed. We are diagnosing more than we need to, and we are subsequently overtreating,” Bleyer said.

A new finding of uncertain significance is the proportion of cancer in AYAs that is not considered malignant, such as ductal carcinoma in situ (DCIS) of the breast and low-grade brain tumors (gliomas, craniopharyngioma, meningioma). Data from the Surveillance, Epidemiology and End Results (SEER) program indicate that about 15 percent of AYA cancers—one in every six to seven patients—are reported as non-malignant, the highest proportion of all age groups. Some of these non-malignant cancers are nonetheless lethal. “We need to look into this problem,” Bleyer said.

Melissa Hudson, director of cancer survivorship and division coleader for the cancer prevention and control program at St. Jude Children's Research Hospital, showed that survival improved for those diagnosed with cancer in their 20s in the period 1993–1998 compared to those diagnosed during 1975–1980 (Veal et al., 2010). Survival decreased during the same time span for those diagnosed in their 30s.

More recent trends in cancer incidence, survival, and mortality among AYA patients are currently being assessed. The NCI held a meeting in September 2013, to examine current science and research gaps in AYA oncology. The workshop utilized five working groups that reviewed the available data on the epidemiology (incidence, survival, mortality) of select AYA cancers, as well as evidence related to basic biology, clinical trial enrollment, models of care, and health-related quality of life/symptom management for this population.

Footnotes

2

Human homolog B of v-raf (rapidly accelerated fibrosarcoma viral oncogene).