Premature Aging in Young Cancer Survivors

Saro H. Armenian; Christopher J. Gibson; Russell C. Rockne; Kirsten K. Ness

Disclosures

J Natl Cancer Inst. 2019;111(3):226-232. 

In This Article

Abstract and Introduction

Abstract

Advances in early detection, treatment, and supportive care have resulted in an estimated 16 million cancer survivors who are alive in the United States today. Outcomes have notably improved for children with cancer as well as young adults with hematologic malignancies due, in part, to the intensification of cancer treatment, including the use of hematopoietic cell transplantation. Emerging evidence suggests that these cancer survivors are at risk for premature aging, manifesting as early onset of chronic health conditions and a higher risk of mortality compared with the general population. Although the pathophysiology of premature aging in these survivors has not been fully elucidated, emerging concepts in aging research could help shed light on this phenomenon. Longitudinal studies are needed to better characterize aging in these survivors, setting the stage for much-needed interventions to halt the trajectory of accelerated aging. These efforts will be enhanced through collaborations between translational researchers, clinical oncologists, primary care providers, geriatricians, patient caretakers, and other stakeholders committed to improving the lives of the growing population of survivors.

Introduction

Advances in early detection, treatment, and supportive care have contributed to a rapidly growing number of cancer survivors. It is estimated that there are currently 16 million cancer survivors alive in the United States today, a number that will exceed 18 million by the year 2022.[1,2] A majority (≥70%) are long-term cancer survivors (alive ≥5 years from diagnosis), and roughly 15% have lived 20 years or more after their diagnosis.[1–3] For children with cancer, 5-year overall survival now exceeds 80%, and it is projected that by the year 2020 there will be more than 500 000 survivors of childhood cancer living in the United States.[4–6] For patients who undergo hematopoietic cell transplantation (HCT), more than 70% who survive the first 2 years after HCT are expected to become long-term survivors,[7–9] which is remarkable considering many patients undergo HCT to treat refractory disease. Unfortunately, improvement in survival has not always resulted in improvement in other health-related outcomes.

Numerous studies, many conducted among elderly (≥65 years old) survivors and some in younger survivor cohorts, have described the high burden of chronic health conditions that develop after cancer treatment, with a well-documented phenotype of premature aging among older survivors[10–14] and a phenotype suggestive of premature aging among younger survivors.[15–18] In these survivors, there is a dose-dependent effect of treatment that interacts with a priori physiologic health to affect outcomes, whereby the more intensive the cancer-directed treatment or more vulnerable the physiologic state of the patient, the steeper the decline in health and quality of life.[4,10,19] For older cancer survivors, signs, symptoms, and markers of aging largely occur in a background of preexisting comorbidities, making it a challenge to disentangle the contributions of aging and cancer and its treatments on posttreatment health-related outcomes.

Unlike the elderly, children diagnosed with cancer or young adults who undergo HCT typically do not carry a high burden of comorbid health conditions at diagnosis. The implications of premature aging in these survivors are broad, impacting both the long-term quantity (lifespan) and quality (healthspan) of life after treatment. For example, some may develop treatment-related chronic health conditions before the age threshold for screenings in the general population (eg, breast cancer at age 40 years; colon cancer at age 50 years; loss of white matter integrity and development of associated cognitive loss not expected in a young adult),[20–25] highlighting the need for tailored risk-based screening for health conditions typically associated with aging. Although it is not clear that the trajectory of aging or associated biomarkers are different in cancer survivors treated during childhood, adolescence, or young adulthood when compared to cancer survivors treated in later decades, we speculate that there are differences given that cancer therapy in a younger population is delivered to a physiologic system that is extremely active (still developing) and that starts with less accumulated damage (eg, somatic mutations) and fewer chronic diseases. In this commentary, we provide an overview of aging and cancer survivorship with a focus on children, adolescents, and young adults, including those treated with HCT. We also examine how biomarkers can be utilized to understand and screen for premature aging, and we discuss strategies to mitigate adverse health-related outcomes.

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