At the Heart of Adolescent and Young Adult Cancer Survivorship.

The declaration of the war on cancer 45 years ago sharply focused basic and clinical research on improving therapies, advancing multi-institutional clinical trials through the cooperative group structure, furthering testing and the introduction of new agents, and improving supportive care for individuals diagnosed with a malignancy. These strides have increased the number of cancer survivors to more than 14 million in the United States today. The emergence of a population formerly treated for cancer has presented the medical community with a number of unforeseen, perhaps welcome, challenges of providing care to individuals treated for a life-threatening illness now returning to and requiring primary care surveillance and screening as would be recommended for any adult in the general community. Many issues are the focus of active research, such as concurrently providing oncologic and primary care, appropriate disease surveillance, appropriate screening for therapy-related late effects, and the need to provide psychologic and social support for patients returning to school, work, and family life. These challenges vary depending on the particular cancer diagnosis, therapies received, age at treatment, sex, and any individual patient’s particular social structure and support system. Furthermore, data yet to be fully investigated may illuminate genetic-related risks for particular adverse late outcomes Multidisciplinary research programs have developed in most academic centers to address these questions and ensure the ongoing health maintenance of cancer survivors. Following cancer survivors long term presents its own challenges, and to date most late outcomes research has come from survivors of pediatric cancers. Large cohort studies following childhood cancer survivors or registry-based analyses have elucidated the organ dysfunction, chronic health conditions, and neurocognitive impairments many of these children encounter later in life. Subset analyses from these larger cohorts have been used to draw conclusions about patients treated in the adolescent and young adult age ranges and occasionally to extrapolate to survivors of adult-onset cancers. Although the majority of adolescents and young adults enjoy good health, a diagnosis of cancer, as occurs annually for nearly 70,000 individuals age 15 to 39 years, presents unique challenges for treatment and long-term health. Diagnoses in this age group are heterogeneous, ranging from mostly leukemia, lymphoma, germ cell tumors, and thyroid cancers in those 15 to 24 years old to breast cancer, cervical cancer, and melanoma among those 25 to 39 years old. Recognizing the unmet needs of this age group, the National Cancer Institute and Livestrong Foundation convened the Adolescent and Young Adult Oncology Progress Review Group 10 years ago in an effort to focus research on this particular population. Although survival rates have lagged behind those of other age groups, improvements are beginning to be realized, and an increasing number of these young people are becoming longterm cancer survivors. The number of life-years saved has significant societal implications, making preservation of health and reduction of morbidity in this population of particular importance. Interrogating the large Kaiser Permanente Southern California database, Chao et al, in the article that accompanies this editorial, retrospectively analyzed the medical records of 5,673 adolescent and young adult cancer survivors, matching them to 57,617 controls without cancer, for cardiovascular outcomes, defined as the composite of coronary artery disease, congestive heart failure, and stroke. These investigators were able to focus their analysis on those diagnosed in the 15to 39-year-old age range, thus capturing the most common diagnoses within this age group. Just over half were survivors of breast cancer, thyroid carcinoma,melanoma, and testicular cancer, at amean age of 33 years, and only an average of 6 years from diagnosis. Limited by a lack of treatment data, the study was able to include a variety of significant covariates, including demographic, cardiovascular (diabetes, hypertension, dyslipidemia), and lifestyle (smoking, overweight/obesity) factors. Linking the electronic health record with clinical databases inclusive of International Classification of Diseases 9th and 10th revisions codes and Current Procedural Terminology 4th edition procedure codes, laboratory data, and medications across the health system allowed investigators to confirm these covariates. Adjusting for known risk factors, investigators identified an increased incidence rate ratio (IRR) for cardiovascular disease (IRR, 2.37; 95% CI, 1.93 to 2.93) among all adolescent and young adult cancer survivors as well as among breast (IRR, 3.63; 95% CI, 2.41 to 5.47), lymphoma (IRR, 2.79; 95% CI, 1.37 to 5.65), leukemia (IRR, 4.23; 95% CI, 1.73 to 10.31), and melanoma (IRR, 2.94; 95% CI, 1.45 to 5.99) survivors. Survivors of thyroid cancer did not have a significantly elevated IRR. The authors assessed selected diagnostic groups as the sample sizes allowed. Interestingly, apparently the number of events in the testicular cancer survivors, a group with known adverse cardiovascular outcomes, was not sufficient for assessment, perhaps as a result of the shorter follow-up.