Respiratory medicine · 2025
Cyclophosphamide is not associated with clinically relevant late pulmonary dysfunction in Dutch survivors of childhood cancer - The DCCSS-LATER 2 PULM sub-study.
СтатьяМногоцентровое исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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van Kalsbeek R J, Feijen E A M, Bresters D, Kremer L C M, Pluijm S M F, Asogwa O A, Dulmen-den Broeder E van, van den Heuvel-Eibrink M M, Janssens G O, Tissing W J, Loonen J J, Neggers S J C M M, van der Pal H J H, Ronckers C M, Teepen J C, de Vries A C H, Louwerens M, van der Heiden-van der Loo M, Prevaes S M P J, Versluys A B
Аннотация
BACKGROUND: Treatment for childhood cancer may increase the risk of long-term pulmonary complications and dysfunction. Pulmonary surveillance is recommended after established pulmonary toxic exposures, including bleomycin, busulfan, carmustine (BCNU), lomustine (CCNU), radiotherapy to a field exposing the lungs, and pulmonary surgery. However, the role of cyclophosphamide as a pulmonary toxic agent is debated.
AIM: To establish whether cyclophosphamide is associated with late pulmonary dysfunction among survivors of childhood cancer.
METHODS: In this multicenter Dutch Childhood Cancer Survivor Study (DCCSS)-LATER 2 PULM sub-study, we included 828 survivors with a median follow-up of 26.6 years, treated with cyclophosphamide and/or established pulmonary toxic treatment, or neither. Pulmonary function tests were used to measure the primary outcomes of diffusion impairment (diffusing capacity for carbon monoxide (DLCO) z-score), restriction (total lung capacity (TLC) z-score), and obstruction (forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) z-score). Secondary outcomes comprised chronic cough, recurrent respiratory tract infections, shortness of breath, and supplemental oxygen need.
RESULTS: Diffusion and restrictive abnormalities were highly prevalent among those treated with established pulmonary toxic treatment, with cyclophosphamide (41.0 % and 50.4 %, respectively) and without (34.3 % and 41.9 %, respectively), and occurred less frequently in survivors treated with cyclophosphamide only (12.9 % and 7.3 %, respectively) or in survivor controls (9.9 % and 12.4 %, respectively). In multivariable analyses, cyclophosphamide did not have a clinically relevant effect on the primary or secondary outcomes.
CONCLUSIONS: This study suggests that cyclophosphamide is not associated with clinically relevant pulmonary dysfunction in long-term childhood cancer survivors.
AIM: To establish whether cyclophosphamide is associated with late pulmonary dysfunction among survivors of childhood cancer.
METHODS: In this multicenter Dutch Childhood Cancer Survivor Study (DCCSS)-LATER 2 PULM sub-study, we included 828 survivors with a median follow-up of 26.6 years, treated with cyclophosphamide and/or established pulmonary toxic treatment, or neither. Pulmonary function tests were used to measure the primary outcomes of diffusion impairment (diffusing capacity for carbon monoxide (DLCO) z-score), restriction (total lung capacity (TLC) z-score), and obstruction (forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) z-score). Secondary outcomes comprised chronic cough, recurrent respiratory tract infections, shortness of breath, and supplemental oxygen need.
RESULTS: Diffusion and restrictive abnormalities were highly prevalent among those treated with established pulmonary toxic treatment, with cyclophosphamide (41.0 % and 50.4 %, respectively) and without (34.3 % and 41.9 %, respectively), and occurred less frequently in survivors treated with cyclophosphamide only (12.9 % and 7.3 %, respectively) or in survivor controls (9.9 % and 12.4 %, respectively). In multivariable analyses, cyclophosphamide did not have a clinically relevant effect on the primary or secondary outcomes.
CONCLUSIONS: This study suggests that cyclophosphamide is not associated with clinically relevant pulmonary dysfunction in long-term childhood cancer survivors.