Longitudinal Changes in Pulmonary Function After Treatment of Childhood Cancer: A Report from the St. Jude Lifetime Cohort Study
Neel S Bhatt, Lu Xie, Kendrick Li, DeoKumar Srivastava, Gregory T Armstrong, Andrew M Davidoff, Stephanie B Dixon, Amar Gajjar, I-Chan Huang, Melissa M Hudson, Matthew J Krasin, Mary E (Beth) McCarville, Thomas E Merchant, Daniel A Mulrooney, Kirsten K Ness, Leslie L Robison, Saumini Srinivasan, Daniel M Green, Dennis C StokesAbstract
Rationale/ Objectives
Data on longitudinal changes in pulmonary function in long-term childhood cancer survivors remain limited. Using a well-characterized cohort of childhood cancer survivors, we analyzed these changes through serial PFT assessments among those exposed to pulmonary-toxic therapy, with available radiation dosimetry data.
Methods
In this single-institutional, hospital-based, retrospective cohort study, Z-scores for FEV1, TLC, and DLCOcorr were calculated, with Z-score ≤-1.65 being considered abnormal. Patient and treatment-related risk-factors for worsening or persistently abnormal Z-scores were assessed. Associations between Z-scores and changes in six-minute walk distance (6MWT), QOL, and persistence or new development of cardiopulmonary and fatigue-related symptoms were studied.
Results
Among 606 survivors at a median of 27.2 (range 11.3-54.0) years from diagnosis, abnormal FEV1, TLC, and DLCOcorr Z-scores were noted in 49.5%, 51.4%, and 38.0%, respectively. Among those with ≥2 PFT assessments (n = 480), all Z-scores declined, most pronounced at ≥ 30-years from diagnosis. Each 10% increase in lung tissue receiving ≥10 Gy radiation was associated with declining or persistently abnormal FEV1 at 5-years after first PFT (OR 1.18, 95%CI 1.03-1.35). Obesity was associated with declining FEV1 and TLC; Smoking status was associated with declining DLCOcorr Z-scores. Worsening or persistently abnormal Z-scores for FEV1, TLC, and DLCOcorr were associated with decline in 6MWT distance and self-reported physical function. Decline in Z-scores were associated with greater odds of persistent or newly developed shortness of breath with exercise. Decline in DLCOcorr was associated with chronic cough, faintness, and dizziness.
Conclusions
Pulmonary function declined over time in adult survivors of childhood cancer exposed to pulmonary-toxic therapy, with radiation exposure portending higher risk. Declines were associated with reduced exercise capacity and QOL and increased cardiopulmonary and fatigue-related symptoms. Our findings help identify survivors who may benefit from interventions to preserve pulmonary function.