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.