Pulmonary defects common among childhood cancer survivors
Survivors of pediatric cancers who underwent pulmonary-compromising therapies demonstrated a significant risk for long-term pulmonary complications, according to study results.
Females and patients who underwent high-dose chest radiation faced a particularly increased risk for diffusion capacity declines over time and may benefit from subsequent monitoring, according to the researchers.
“Five-year survivors have a nearly ninefold excess risk of dying as a result of pulmonary compromise when compared with age- and sex-matched individuals without a history of cancer,” Saro H. Armenian, DO, of the City of Hope National Medical Center in Duarte, California, and colleagues wrote. “The cumulative incidence of pulmonary disease increases with time from diagnosis, suggesting that childhood cancer survivors increasingly face pulmonary morbidity as they age.”
Saro H. Armenian
Armenian and colleagues evaluated data from 121 survivors of pediatric cancer (median age at diagnosis, 16.5 years; median age at examination, 32.3 years). The primary diagnoses of population included Hodgkin’s lymphoma (33.9%), acute lymphoblastic leukemia (16.5%) and acute myeloid leukemia (14.1%). Common forms of treatment included chest radiation plus pulmonary-toxic chemotherapy (48%) and hematopoietic stem cell transplantation (52.9%).
Researchers compared data from the survivors with a cohort of 43 healthy control participants who were well-matched regarding age, sex, BMI, employment, smoking history and heart disease status. A greater proportion of the control cohort was non-Hispanic white (51.2% vs. 37.2%; P < .01) and had health insurance (93% vs. 71.9%; P < .01).
Cancer survivors underwent a baseline pulmonary function test and subsequently completed a modified question version of the Medical Research Council dyspnea questionnaire after a median of 5 years (range, 1-10.3).
Survivors who answered “yes” to two or more questions at the second evaluation were determined to have symptomatic pulmonary disease. Researchers compared the survivor and control cohorts at the time of the second evaluation.
Overall, survivors of pediatric cancer were significantly more likely to experience restrictive defects (OR = 6.5; 95% CI, 1.5-28.4) and diffusion abnormalities (OR = 5.2; 95% CI, 1.8-15.5) compared to the control cohort.
Symptomatic disease was more prevalent among cancer survivors (21.5% vs. 4.7%; P < .01); however, there was no significant difference in the incidence of obstructive lung disease between the two cohorts (4.1% vs. 0%).
Restrictive defects were significantly more common among survivors aged 16 years or younger at time of diagnosis (OR = 3; 95% CI, 1.2-7.8) and those treated with more than 20 Gy of chest radiation compared with no chest radiation (OR = 5.6; 95% CI, 1.5-21).
Diffusion abnormalities were significantly associated with female sex (OR = 3.9; 95% CI, 1.7-9.5) and chest radiation dose (≤ 20 Gy: OR = 6.4; 95% CI, 1.7-24.4; > 20 Gy: OR = 11.3; 95% CI, 2.6-49.5). Researchers noted that among survivors with normal baseline pulmonary function tests, women (P = .02) and survivors who received more than 20 Gy doses of chest radiation (P ˂ .01) demonstrated significant declines in diffusion function over time.
The researchers acknowledged that survivors included in the analysis were those judged to be at risk based on the Children’s Oncology Group Long-Term Follow Up Guidelines, and thus, patients who underwent treatment regimens not associated with pulmonary toxicity were not included. The researchers also were unable to obtain specific information on radiation dosimetry.
“These findings may facilitate the development of targeted screening approaches for patients at high risk for progressive pulmonary disease such as diffusion capacity abnormality, setting the stage for the development of therapeutic or lifestyle interventions to improve pulmonary function in survivors at highest risk for symptomatic respiratory comorbidities,” Armenian and colleagues concluded. – by Cameron Kelsall
Disclosure: One researcher reports research funding from Merck, Sharp & Dohme.