Effects of pulmonary function of whole lung irradiation for Wilm's tumour in children.

Abstract

The effect of whole lung irradiation on lung function was investigated in 48 children treated for Wilm's tumour with pulmonary metastases. Lung function tests were performed before irradiation and were repeated annually for as long as possible, the length of follow-up varying from two to 17 years. A reduction in both lung volume and in dynamic compliance was clearly observed. In some patients these changes occurred in the early post-irradiation months, but in most the decrease observed progressed over longer periods of time. Static pressure volume curves, bloodgases, and carbon monoxide transfer were normal. These findings make it unlikely that postirradiation pulmonary fibrosis was involved. Another explanation for the decreased lung volume and dynamic compliance might be failure of alveolar multiplication. Muscular injury is unlikely as the patients were able to produce normal transthoracic pressures. A failure of chest wall growth is also possible and would explain the progressive restrictive impairment but not the early lung function changes. It is suggested that the early effects detected in some patients were the result of lung injury and that later effects resulted from impaired chest wall growth.Although the effects of pulmonary irradiation on lung function have been extensively investigated in adults, reports on the effects on respiratory function of whole lung irradiation are relatively few and there have been no reports of detailed, repeated lung function tests after this type of irradiation.In contrast to adults, young children are in a period of rapid lung and skeletal growth and the effect of pulmonary irradiation might be a failure of alveolar development resulting from impaired cellular proliferation, thus decreasing the number of alveoli. The aim of this study was to detect the shortand long-term pulmonary function changes in young children who received whole lung irradiation at doses which were therapeutically efficient but close to tolerance and we have tried to characterise the physiopathological mechanisms of the changes observed. Actinomycin D which enhances the effects of irradiation, was administered consecutively.1

Pulmonary complications in survivors of childhood and adolescent cancer

“…5,6,19 Furthermore, increased occurrence of pulmonary abnormalities has been associated with dose-intensive protocols that include radiation therapy and/or high cumulative doses of chemotherapy in survivors of leukemia, 20 -22 rhabdomyosarcoma, 18 and Hodgkin disease [23][24][25] and in individuals who undergo bone marrow transplantation. 26,27 Based on self-reports, we identified a high incidence of significant pulmonary pathology, including lung fibrosis, pleurisy, and use of supplemental oxygen among childhood cancer survivors.…”

“…3,4 Early studies of children who were treated for Wilms tumor suggested that radiation treatment at an early age led to significant reductions both in lung volume and in dynamic compliance over time as well as decreased chest wall growth. 5,6 Two studies of individuals who were treated for Hodgkin disease and received radiation to the lung showed an increase in the subsequent risk of lung carcinoma, with the risk continuing to increase with time after the diagnosis; 7 the risk was increased further by exposure to alkylating agents. 8 Pulmonary toxicity due to chemotherapy, like that associated with radiotherapy, also follows a pattern of an early phase resulting in interstitial lung injury occurring up to several months after treatment and a late phase with pulmonary fibrosis as the most common sequela.…”

Pulmonary Outcomes in Survivors of Childhood Cancer

“…Table 3 lists the 22 reports published from January 1970 to June 2010 on radiation-induced pulmonary late effects among survivors of childhood cancer. Data from early studies on children treated for metastatic Wilms tumor demonstrate that irradiation of the thorax primarily affects the lung parenchyma and results in reduced lung volume, 13,14 impaired dynamic compliance, 14 and deformity of both the lung and chest wall. 12,14 The diffusing capacity of the lung for carbon monoxide (D lco ) may also be reduced.…”

“…Data from early studies on children treated for metastatic Wilms tumor demonstrate that irradiation of the thorax primarily affects the lung parenchyma and results in reduced lung volume, 13,14 impaired dynamic compliance, 14 and deformity of both the lung and chest wall. 12,14 The diffusing capacity of the lung for carbon monoxide (D lco ) may also be reduced. 12 In 1992, Attard-Montalto et al 20 described lung function in eight survivors of Wilms tumor (follow-up, 14.8 years) who had received whole-lung irradiation at 15.3 Ϯ 1.8 gray (Gy) in 10 to 14 daily fractions , and actinomycin, a radiomimetic chemotherapeutic agent.…”

Adverse Late Effects of Childhood Cancer and Its Treatment on Health and Performance

“…When symptomatic, it presents with dyspnea and a nonproductive cough (52, 88). Studies of children with cancer who received radiation show a significant reduction in lung function and dynamic lung compliance, likely owing to impaired cell proliferation and failed alveolar development (10,136,219). Pulmonary toxicity occurs after exposure to bleomycin, mitomycin-C, nitrosoureas such as BCNU (carmustine) and CCNU (lomustine), busulfan, and cyclophosphamide (54).…”