Long-Term Pulmonary Function in Survivors of Childhood Cancer

Abstract

Purpose This study was undertaken to determine the magnitude of pulmonary dysfunction in childhood cancer survivors when compared with healthy controls and the extent (and predictors) of decline over time. Patients and Methods Survivors underwent baseline (t1) pulmonary function tests, followed by a second comprehensive evaluation (t2) after a median of 5 years (range, 1.0 to 10.3 years). Survivors were also compared with age- and sex-matched healthy controls at t2. Results Median age at cancer diagnosis was 16.5 years (range, 0.2 to 21.9 years), and time from diagnosis to t2 was 17.1 years (range, 6.3 to 40.1 years). Compared with odds for healthy controls, the odds of restrictive defects were increased 6.5-fold (odds ratio [OR], 6.5; 95% CI, 1.5 to 28.4; P < .01), and the odds of diffusion abnormalities were increased 5.2-fold (OR, 5.2; 95% CI, 1.8 to 15.5; P < .01). Among survivors, age younger than 16 years at diagnosis (OR, 3.0; 95% CI, 1.2 to 7.8; P = .02) and exposure to more than 20 Gy chest radiation (OR, 5.6; 95% CI, 1.5 to 21.0; P = .02, referent, no chest radiation) were associated with restrictive defects. Female sex (OR, 3.9; 95% CI, 1.7 to 9.5; P < .01) and chest radiation dose (referent: no chest radiation; ≤ 20 Gy: OR, 6.4; 95% CI, 1.7 to 24.4; P < .01; > 20 Gy: OR, 11.3; 95% CI, 2.6 to 49.5; P < .01) were associated with diffusion abnormalities. Among survivors with normal pulmonary function tests at t1, females and survivors treated with more than 20 Gy chest radiation demonstrated decline in diffusion function over time. Conclusion Childhood cancer survivors exposed to pulmonary-toxic therapy are significantly more likely to have restrictive and diffusion defects when compared with healthy controls. Diffusion capacity declines with time after exposure to pulmonary-toxic therapy, particularly among females and survivors treated with high-dose chest radiation. These individuals could benefit from subsequent monitoring.

Pulmonary Function after Treatment for Childhood Cancer. A Report from the St. Jude Lifetime Cohort Study (SJLIFE)

“…This difference may be related, in part, to the higher proportions of survivors with Hodgkin lymphoma and of those who had undergone pulmonary metastasectomy in the SJLIFE cohort than in the Dutch and North American studies (11,13). In contrast to restrictive pulmonary deficits, we observed a low prevalence of obstructive pulmonary deficits (0.8%; 5 of 606), similar to that previously reported (11,13).…”

“…The prevalence of restrictive pulmonary deficits in our cohort differs from previous investigations of pulmonary outcomes among childhood cancer survivors who underwent clinical assessments. We identified restrictive pulmonary impairment in 31.2% (186 of 597) of SJLIFE childhood cancer survivors, compared with 18.7% (28 of 150) of Dutch childhood cancer survivors (11) and 21.5% (26 of 121) of North American childhood cancer survivors (13). This difference may be related, in part, to the higher proportions of survivors with Hodgkin lymphoma and of those who had undergone pulmonary metastasectomy in the SJLIFE cohort than in the Dutch and North American studies (11,13).…”

“…We identified restrictive pulmonary impairment in 31.2% (186 of 597) of SJLIFE childhood cancer survivors, compared with 18.7% (28 of 150) of Dutch childhood cancer survivors (11) and 21.5% (26 of 121) of North American childhood cancer survivors (13). This difference may be related, in part, to the higher proportions of survivors with Hodgkin lymphoma and of those who had undergone pulmonary metastasectomy in the SJLIFE cohort than in the Dutch and North American studies (11,13). In contrast to restrictive pulmonary deficits, we observed a low prevalence of obstructive pulmonary deficits (0.8%; 5 of 606), similar to that previously reported (11,13).…”

“…The reported prevalence of pulmonary dysfunction among adult childhood cancer survivors has varied, depending on cohort composition, treatment diversity, time from exposure, and method of ascertainment (11)(12)(13). Studies of larger childhood cancer survivor cohorts have been limited by selfreported ascertainment of outcomes (14).…”

“…predicted less than 75% (13) or the combination of FEV 1 /FVC greater than or equal to the lower limit of normal (LLN) and FVC less than the LLN (34) were classified as restrictive lung defects. Obstructive lung defects were defined by either prebronchodilator FEV 1 /FVC less than 0.70 (35) or prebronchodilator FEV 1 /FVC less than the LLN (34).…”