Introduction
Over the last few decades, improved antineoplastic therapies have resulted in significant improvements in cancer survival rates. For childhood and adolescent cancers, the 5-year survival has risen to over 85%1, creating a growing population of childhood cancer survivors (CCS). In 2015, over 360,000 CCS were living in the United States1.
Although treatment regimens, which can include radiation, chemotherapy, and surgery, are highly effective, they can also cause significant long-term morbidity and mortality as these young survivors age. Secondary malignancies and organ dysfunction can develop just a few years after the successful cure of the primary cancer2. By thirty years post- diagnosis, over 70% of CCS will suffer from a chronic health condition3.
While pulmonary dysfunction is the second leading cause of mortality in CCS4, it is also one of the most common morbidities of treatment, with a prevalence of 65.2% in adulthood5. The increase in prevalence of pulmonary morbidity over time may be due to lung injury occurring during a period of lung development, leaving a deficit in growth potential, thereby amplifying the natural decline in lung function with age6. Alternatively, lungs may be more susceptible to the toxic effects of radiation and immunosuppression during this growth phase leading to ongoing damage even after completion of treatment. Common pulmonary toxic therapies, including bleomycin, busulfan, lomustine, carmustine, and thoracic radiation have been shown to result in sequelae including pulmonary fibrosis, and interstitial pneumonitis7 which can result in progressive lung damage. Radiation can also cause hypoxia and oxidative stress, leading to long-term tissue damage, and chronic inflammation8,9.
Improved understanding of the early trajectory of pulmonary dysfunction in CCS can improve early detection and facilitate treatment to prevent or reduce associated morbidities, as well as improve decision-making surrounding the use and dosage of pulmonary toxic therapies in certain subpopulations during treatment.
In this retrospective cohort study, we sought to better understand the early trajectory of lung function and explore impacting factors in children who received pulmonary toxic cancer therapies. Through cross-sectional pediatric and adult studies, we know that lung function is altered in this population, but the onset and early trajectory of pulmonary function change is not well characterized.