Pulmonary Radiation Injury: Identification of Risk Factors Associated with Regional Hypersensitivity

Abstract

Effective radiation treatment of thoracic tumors is often limited by radiosensitivity of surrounding tissues. Several experimental studies have suggested variations in radiosensitivity of different pulmonary regions. Mice and rat studies in part contradict each other and urge for a more detailed analysis. This study was designed to obtain a more comprehensive insight in radiation injury development, expression, and its regional heterogeneity in lung. The latter is obviously highly critical for optimization of radiotherapy treatment plans and may shed light on the mechanisms of lung dysfunction after irradiation. Six different but volume-equal regions in rat lung were irradiated. Whereas the severity of damage, as seen in histologic analysis, was comparable in all regions, the degree of lung dysfunction, measured as breathing rates, largely varied. During the pneumonitic phase (early : 6-12 weeks), the most sensitive regions contained a substantial part of alveolar lung parenchyma. Also, a trend for hypersensitivity was observed when the heart lay in the irradiation field. In the fibrotic phase (late: 34-38 weeks), lung parenchyma and heartencompassing regions were the most sensitive. No impact of the heart was observed during the intermediate phase (16-28 weeks). The severity of respiratory dysfunction after partial thoracic irradiation is likely governed by an interaction between pulmonary and cardiac functional deficits. As a repercussion, more severe acute and delayed toxicity should be expected after combined lung and heart irradiation. This should be considered in the process of radiotherapy treatment planning of thoracic malignancies. (Cancer Res 2005; 65(9): 3568-76)

Limiting the risk of cardiac toxicity with esophageal-sparing intensity modulated radiotherapy for locally advanced lung cancers

“…Cardiac irradiation is associated with pulmonary dysfunction (20,21). Additionally, the benefit received by reducing the amount of irradiated lung is enhanced by reducing the dose received by the heart (22).…”

Structural and functional alterations in the rat lung following whole thoracic irradiation with moderate doses: Injury and recovery

“…Respiratory frequency is a well validated marker of radiation induced lung damage in rodents (Van Eerde et al 2001, Novakova-Jiresova et al 2005). In our experiments rats immobilized in a plexiglas jig were placed in a transparent, airtight box.…”

Analysis of normal tissue complication probability of the lung using a reliability model

“…Travis and colleagues [11 Á13] have in particular contributed to the investigation of the nature of the volume effect in lung and the tolerance doses by their experiments in mouse lung, and they have demonstrated a spatial heterogeneity in the radiosensitivity of the mouse lung. A pronounced variation in radiation sensitivity throughout the lung was demonstrated also in rats by Novakova-Jiresova and colleagues [14]. There may be different explanations for the observed volume effects; a spatial heterogeneity in FSU distribution, a spatial heterogeneity in radiation sensitivity of the individual FSUs, and lastly, a spatial heterogeneity in tissue architecture.…”

“…However, Khan et al [20] ruled out the possibility that irradiation of parts of the abdomen (inferior to the lung) might be responsible for the out-of-field damage in rat lung. Novakova-Jiresova et al [14] observed higher frequency of lung complications in the apex of rat lung as compared to the lung base using a functional endpoint. However, they failed to identify corresponding variations in histo-pathological damage.…”