Longitudinal Changes in Pulmonary Function After Treatment of Childhood Cancer: A Report from the St. Jude Lifetime Cohort Study.
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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.