Loss of pulmonary function after carbon ion irradiation of the rat lung

Radiotherapy is a common and effective treatment for many cancers. For most cancers, however, normal tissues are inevitably co-irradiated. This may lead to severe toxicity. For tumours in e.g. the thoracic region, this limits treatment dose and efficacy. Therefore, development of particle therapy aimed at minimizing dose and volume to which the normal tissues are irradiated. Particles such as carbon ions lose most of their energy in the target volume resulting in a superior physical dose distribution compared to classically-used photons. In addition, the biological effect of particle dose differs from that of photon dose. To translate currently-applied photon therapy to equivalent particle therapy, these differences in biological effect need to be corrected for. The uncertainty in models predicting these differences is the main source of uncertainties in the prescribed dose of particle therapy [1]. The testing and development of these models requires e.g. data on the response of normal tissues to carbon ion irradiation. Therefore in the present project an established model of partial rat lung irradiation [2] was used to determine the response of the rat lung to carbon ions. The present report describes a first dose-finding study. Groups of 3 rats were irradiated on the whole lung or 50% of the lung with plateau or spread-out-Bragg peak carbon ions. As a measure of pulmonary function, respiratory rate was measured bi-weekly up to 28 weeks after irradiation. Early (4 – 12 weeks after irradiation) increases in breathing rate result predominantly from an acute inflammatory response [3]. At later time points (16 – 28 weeks after irradiation) increases are due to chronic inflammation and fibrosis. As a measure of the loss of pulmonary function the mean increase in respiratory rate in these time spans compared to the mean respiratory rate in 0 – 2 weeks is calculated. Both irradiation of the whole lung and 50% of the lung resulted in loss of pulmonary function in the early time span. Similar to observations after photon irradiation [4], this response was only followed by a fibrotic response after irradiation of 50% of the lung, where higher dose levels have been assessed Observations after irradiation of the whole lung with spread-out Bragg peak ions showed similar patterns in the overlapping dose range (figure 2). The dose range used for irradiation of 50% of the lung did not result in any significant response. Histological analysis of tissue of animals sacrificed at 8 weeks after irradiation is in progress. Based on these results more detailed dose-volumeresponse studies will be designed and performed to obtain the data required for the development of risk models for carbon ion irradiation of the lung to facilitate optimized application of carbon ions in thoracic radiotherapy.