[Risk factors for lung toxicity in pediatric cancer survivors]

Our objectives were to determine the prevalence of alterations in lung function among pediatric cancer survivors with known risk factors and to establish clinical and imaging correlations, as well as to establish follow-up criteria.

Cancer survivors diagnosed at the Pediatric Oncology Unit between 1971 and 1997 who fulfilled at least one of the following criteria were eligible: 1) primary lung or thoracic wall neoplasm; 2) lung metastasis at diagnosis or later, or; 3) irradiation of mediastinum and/or lung fields. Assessment included respiratory symptomatology questionnaire, physical examination, forced spirometry, static lung volumes, maximal static respiratory pressures, single breath CO diffusing capacity, pulse oximetry and imaging studies.

Thirty-five (14 females and 21 males) out of 41 survivors were assessed. Mean age at diagnosis, evaluation and follow-up were 9 (1-14), 18 (10-28) and 9 (3-27) years, respectively. The diagnoses included pleuropulmonary blastoma (1), chest wall Ewing's sarcoma (1), Hodgkin's disease (18), nephroblastoma (7), yolk-sac tumor (2), acute leukemia2), non-Hodgkin's lymphoma (1), rhabdomyosarcoma (1), coriocarcinoma of the ovary (1) and osteosarcoma (1). Thirteen patients presented lung metastasis at diagnosis or later. All were administered chemotherapy. Irradiated fields were the mediastinum (dose 20-56 Gy) in 20 cases, the lung (8-30 Gy) in 6 and the spine (24 Gy) in one. Eight underwent thoracotomy. Fourteen percent were dyspneic when walking at the same rate as a person of the same sex and age (grade 2). Twenty percent had a restrictive ventilatory disorder, but none were obstructive. The presence of dyspnea had sensitivity, specificity, positive predictive values and negative predictive value for the diagnosis of restrictive ventilatory disorder of 67%, 96%, 80% and 93%, respectively. Lung irradiation was associated with an increased risk for the development of restrictive disease. Excluding those who received lung irradiation, survivors under 6 years of age at diagnosis obtained lower spirometric values, lung volumes and DLCO values than survivors aged 6 years or older at diagnosis. There were no differences in pulmonary function values between survivors who received mediastinum irradiation and those who did not. The cumulative dose of cyclophosphamide significantly correlated with FVC, FEV1 and FRC. Pulse oximetry values were > or = 95% in all survivors. Maximal static respiratory pressures were within normal limits in all but one survivors whose other pulmonary function results were normal. Thirty-two percent (11 out of 34) had KCO (diffusing capacity adjusted to alveolar volume) values lower than 80% of reference values. Two survivors of nephroblastoma with pulmonary metastasis and who underwent lung irradiation had radiological signs of lung fibrosis.

Pediatric cancer survivors who were administered intensive chemotherapy and/or lung irradiation are eligible for follow-up of lung function. Those diagnosed before 6 years of age and/or with moderate dyspnea are at high risk of having pulmonary restrictive disease. Imaging studies (chest X-ray) have a low sensitivity that prevents their use as a screening method in the follow-up of cancer survivors.