Birgitta Versluijs

27 Pulmonary complications of childhood cancer treatment A thorough understanding of the complex pulmonary response to injury identifies po- tential targets for intervention, but no such therapy is currently being widely used in clinical practice. An important consideration is that the use of any protective agent in the context of cancer therapy might negatively influence the effect of radiation on the tumor. 9 Clinically radiation injury may result in radiation pneumonitis, an early inflammatory process within 2-4 months after radiation, associated with mild to severe dyspnoea and a non-productive cough. Radiation fibrosis occurs months to years after radiation. Patients may be asymptomatic or present with a varying degree of dyspnoea. Chronic respiratory failure may develop leading to pulmonary hypertension and cor pulmonale. Factors associated with radiation induced lung injury are dosimetric factors, co-admi- nistration of certain chemotherapeutic agents and patient factors like female gender and smoking habits. 8 Within the CCSS cohort there was a cumulative incidence of lung fibrosis at 20 years follow up of 3.5%. Chest radiation therapy was significantly associated with lung fibrosis (RR 4.3; 95% CI 2.9-6.6, p < 0.01), supplemental oxygen use (RR=1.8; 95% CI 1.5-2.2, p< 0.01), recurrent pneumonia (RR 2.2; 95% CI 1, 4-3.5, p< 0.01), and chronic cough (RR = 2.0; 95% CI 1.6-2.4, p< 0.01). There was an association with pulmotoxic chemo- therapy as well (nitrosureas, bleomycin, busulphan and cyclophosphamide), but weaker and mostly in combination with irradiation. This study also showed that the incidence of lung fibrosis, chronic cough and shortness of breath continued to increase up to 25 years from time of diagnosis (Figure 3). 6 A recent study looked at pulmonary outcomes in a cohort of 109 children at least 2 years after therapeutic irradiation of the lung. The cumulative incidence of any pulmonary condition was 70%, mostly pneumonia, chest wall deformity or interstitial lung disease. In multivariate analysis only mean lung irradiation dose (MLD) was associated with ad- verse long term pulmonary outcome (p=0.01), with the probability of having at least one pulmonary complication 5 years after radiation determined as follows: MLD 5 Gy: 53%, MLD 10 Gy: 64%, MLD 15 Gy: 75% and MLD 20 Gy: 84%. Thoracic surgery, age at expo- sure and bleomycin were not predictors in this model. 10 In several other small studies the effect of whole lung irradiation for lung metastases or mantle/involved field/mediastinal radiation for Hodgkin lymphoma was studied. 11–13 Radiation affected lung parenchyma resulted in reduced lung volume, impaired dyna- mic compliance and led to deformity of the chest wall in a dose dependent way. Despite abnormal PFTs in the majority of patients (40%-80%) only 5%-20% of patients were symptomatic. As irradiation damage seems to be dose dependent, one can suspect mild lung injury due to scattering after irradiation of other organs. This issue has not been widely studied so far. 2