Statistical Analysis
Descriptive statistics were summarized for the primary and secondary
outcomes as well as demographics, therapeutic exposures,
hospitalizations and other clinical variables. These summary measures
were compared at baseline for the overall study cohort, at various time
periods both before and after treatment completion, and for females and
males separately. Mean and standard deviation (SD) or median and
interquartile range (IQR) were used for continuous outcomes. Binary
outcomes were summarized using frequency and percentages.
Given the retrospective nature of the study, lung function testing was
performed at variable time points in coordination with treatments or
follow up clinic visits. Therefore, data was summarized in monthly
intervals, to allow comparability of the measurements across patients
and to allow formal longitudinal investigation of the trajectories for
the various outcomes considered. Hence, for each child, the mean outcome
values across all visits within a given month were used as the monthly
value of the outcome.
The visit date for the last recorded cancer treatment (radiation or
chemotherapy) was defined as time zero. Data was summarized into
intervals before and after treatment completion, with the post-treatment
time-period further subdivided into within one year (immediate effect),
between one year and four years (short term effect) and after four years
(long term effect). These periods were defined after careful
consideration of the distribution of the primary and secondary outcomes
and the corresponding time trajectories.
Exploratory analyses were done to investigate lung function trajectories
over time for all three pulmonary function outcomes (FEV1, TLC and
DLCOadj), and to evaluate similarities and differences
in lung function trajectories before and after cancer treatment.
Specifically, lung function trajectory was stratified by sex to
determine if there were any differences between groups. To determine the
potential additive pulmonary toxic effects, sensitivity analyses were
performed to explore differences in lung function trajectories among a
subgroup of children who received both chemotherapy and radiation
therapy.
All analysis was performed using the R statistical software
package14.