R.J. van Kalsbeek , E.A.M. Feijen , D. Bresters , L.C.M. Kremer , S.M.F. Pluijm , O.A. Asogwa , E.van Dulmen-den Broeder , M.M. van den Heuvel-Eibrink , G.O. Janssens , W.J. Tissing , J.J. Loonen , S.J.C.M.M. Neggers , H.J.H. van der Pal , C.M. Ronckers , J.C. Teepen , A.C.H. de Vries , M. Louwerens , M. van der Heiden-van der Loo , S.M.P.J. Prevaes , A.B. Versluys
{"title":"在DCCSS-LATER 2 PULM亚研究中，环磷酰胺与荷兰儿童癌症幸存者临床相关的晚期肺功能障碍无关。","authors":"R.J. van Kalsbeek , E.A.M. Feijen , D. Bresters , L.C.M. Kremer , S.M.F. Pluijm , O.A. Asogwa , E.van Dulmen-den Broeder , M.M. van den Heuvel-Eibrink , G.O. Janssens , W.J. Tissing , J.J. Loonen , S.J.C.M.M. Neggers , H.J.H. van der Pal , C.M. Ronckers , J.C. Teepen , A.C.H. de Vries , M. Louwerens , M. van der Heiden-van der Loo , S.M.P.J. Prevaes , A.B. Versluys","doi":"10.1016/j.rmed.2025.107948","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Aim</h3><div>To establish whether cyclophosphamide is associated with late pulmonary dysfunction among survivors of childhood cancer.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>This study suggests that cyclophosphamide is not associated with clinically relevant pulmonary dysfunction in long-term childhood cancer survivors.</div></div>","PeriodicalId":21057,"journal":{"name":"Respiratory medicine","volume":"237 ","pages":"Article 107948"},"PeriodicalIF":3.5000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cyclophosphamide is not associated with clinically relevant late pulmonary dysfunction in Dutch survivors of childhood cancer – The DCCSS-LATER 2 PULM sub-study\",\"authors\":\"R.J. van Kalsbeek , E.A.M. Feijen , D. Bresters , L.C.M. Kremer , S.M.F. Pluijm , O.A. Asogwa , E.van Dulmen-den Broeder , M.M. van den Heuvel-Eibrink , G.O. Janssens , W.J. Tissing , J.J. Loonen , S.J.C.M.M. Neggers , H.J.H. van der Pal , C.M. Ronckers , J.C. Teepen , A.C.H. de Vries , M. Louwerens , M. van der Heiden-van der Loo , S.M.P.J. Prevaes , A.B. Versluys\",\"doi\":\"10.1016/j.rmed.2025.107948\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>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.</div></div><div><h3>Aim</h3><div>To establish whether cyclophosphamide is associated with late pulmonary dysfunction among survivors of childhood cancer.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>This study suggests that cyclophosphamide is not associated with clinically relevant pulmonary dysfunction in long-term childhood cancer survivors.</div></div>\",\"PeriodicalId\":21057,\"journal\":{\"name\":\"Respiratory medicine\",\"volume\":\"237 \",\"pages\":\"Article 107948\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Respiratory medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0954611125000101\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Respiratory medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0954611125000101","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Cyclophosphamide is not associated with clinically relevant late pulmonary dysfunction in Dutch survivors of childhood cancer – The DCCSS-LATER 2 PULM sub-study
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.
期刊介绍：
Respiratory Medicine is an internationally-renowned journal devoted to the rapid publication of clinically-relevant respiratory medicine research. It combines cutting-edge original research with state-of-the-art reviews dealing with all aspects of respiratory diseases and therapeutic interventions. Topics include adult and paediatric medicine, epidemiology, immunology and cell biology, physiology, occupational disorders, and the role of allergens and pollutants.
Respiratory Medicine is increasingly the journal of choice for publication of phased trial work, commenting on effectiveness, dosage and methods of action.
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