Pulmonary function impairment measured by pulmonary function tests in long-term survivors of childhood cancer
- Renée L Mulder1,
- Nienke M Thönissen2,3,
- Helena J H van der Pal1,4,
- Paul Bresser2,3,
- Wessel Hanselaar5,
- Caro C E Koning6,
- Foppe Oldenburger6,
- Hugo A Heij7,
- Huib N Caron1,
- Leontien C M Kremer1
- 1Department of Paediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands
- 2Department of Pulmonology, Academic Medical Center, Amsterdam, The Netherlands
- 3Department of Respiratory Medicine, OLVG Hospital, Amsterdam, The Netherlands
- 4Department of Medical Oncology, Academic Medical Center, Amsterdam, The Netherlands
- 5Department of Pulmonology, St Franciscus Hospital, Rotterdam, The Netherlands
- 6Department of Radiation Oncology, Academic Medical Center, Amsterdam, The Netherlands
- 7Department of Paediatric Surgery, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands
- Correspondence to Renée L Mulder, Department of Paediatric Oncology, F8-207, Emma Children's Hospital/Academic Medical Center, PO Box 22660, 1100 DD Amsterdam, The Netherlands;
Contributors RLM collected data, wrote the statistical analysis plan, cleaned and analysed the data, and drafted and revised the paper. NMT designed the study protocol, collected data, and drafted and revised the paper. HvdP designed the study protocol, collected data, wrote the statistical analysis plan, contributed to the interpretation of the results and revised the paper. PB and LCMK designed the study protocol, wrote the statistical analysis plan, contributed to the interpretation of the results and revised the paper. WH designed the study protocol, collected data and revised the paper. CCEK, FO, HAH and HNC contributed to the interpretation of the results and revised the paper.
- Received 21 December 2010
- Accepted 30 June 2011
- Published Online First 29 July 2011
Background Childhood cancer survivors (CCSs) have an increased risk of morbidity and mortality. The prevalence and risk factors of pulmonary function impairment were investigated in a large cohort of CCSs treated with potentially pulmotoxic therapy with a minimal follow-up of 5 years after diagnosis.
Methods The study cohort consisted of all adult 5-year CCSs who were treated with bleomycin, pulmonary radiotherapy and/or pulmonary surgery in the Emma Children's Hospital/Academic Medical Center between 1966 and 1996. Pulmonary function tests were performed to diagnose obstructive and restrictive pulmonary function impairment, and diffusion capacity impairment.
Results The study population consisted of 220 out of 248 eligible CCSs, of whom 193 (87.7%) had performed a pulmonary function test at a median follow-up of 18 years after diagnosis. 85 (44.0%) out of 193 CCSs developed a pulmonary function impairment. Pulmonary function impairments occurred in all treatment groups. Most prevalent were restrictive pulmonary function impairment (17.6%) and a decreased carbon monoxide diffusion capacity (39.9%). Multivariate logistic regression models showed that, compared with bleomycin treatment only, treatment with radiotherapy, radiotherapy combined with bleomycin and radiotherapy combined with surgery were associated with the highest risk of pulmonary function impairment.
Conclusions The prevalence of pulmonary function impairment in long-term adult CCSs who received potentially pulmotoxic therapy is high. Bleomycin, pulmonary radiotherapy and pulmonary surgery are all associated with pulmonary function impairment. Pulmonary radiotherapy, especially in combination with bleomycin or surgery, is the most important risk factor. This emphasises the need for adequate counselling and follow-up for this patient population.
- Clinical epidemiology
- drug-induced lung lisease
- lung cancer
- lung cancer chemotherapy
- pulmonary embolism
RLM and NMT contributed equally to this work.
Funding This study was supported by the Foundation of Paediatric Cancer Research (SKK), Amsterdam, The Netherlands. The sponsor had no involvement in the design and execution of the study, in writing the manuscript and in the decision to submit it for publication.
Competing interests None.
Ethics approval The EKZ/AMC institutional review board reviewed and approved the collection of data used for the analyses presented.
Provenance and peer review Not commissioned; externally peer reviewed.