High-dose-rate brachytherapy: dose escalation in three-dimensional miniorgans of the human bronchial wall (original) (raw)
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Changes in Expression of Injury After Irradiation of Increasing Volumes in Rat Lung
International Journal of Radiation Oncology*Biology*Physics, 2007
Purpose: To improve the cure rates of thoracic malignancies by radiation dose escalation, very accurate insight is required in the dose delivery parameters that maximally spare normal lung function. Radiation-induced lung complications are classically divided into an early pneumonitic and a late fibrotic phase. This study investigated the relative dose-volume sensitivity, underlying pathologic findings, and consequentiality of early to late pathologic features. Methods and Materials: We used high-precision, graded dose-volume lung irradiations and followed the time dependency of the morphologic sequelae in relation to overall respiratory function. Results: Two distinct pathologic lesions were identified in the early postirradiation period (6-12 weeks): vascular inflammation and parenchymal inflammation. Vascular inflammation occurred at single doses as low as 9 Gy. This translated into early respiratory dysfunction only when a large lung volume had been irradiated and was reversible with time. Parenchymal inflammation was seen after higher doses only (onset at 16 Gy), progressed into later fibrotic remodeling but did not translate into dysfunction at a 25% lung volume even after single doses up to 36 Gy. Conclusion: Our data imply that a low dose scattered over a large lung volume causes more early toxicity than an extreme dose confined to a small volume. Such findings are crucial for clinical treatment planning of dose escalations and choices for modern radiotherapy techniques.
Dose rate dependence of response of mouse lung to irradiation
British Journal of Radiology, 1985
The dose-rate dependence of lung damage in mice has been studied using LD 5 0 / 5 0 _ 1 8 0 as an index of the incidence of radiation pneumonitis. Mean lethal doses for 60 Co y radiation to the thorax delivered at 100, 25 and 6 cGy/min were 1403, 1923 and 2488 cGy respectively. There were statistically significant differences between values obtained at 6 and 25 cGy/min and between those obtained at 25 and lOOcGy/min. An isoeffect plot of this data on a log-log graph shows the sparing effect of dose rate reduction to be greater for the lung than for more rapidly responding systems (colony forming units of small intestine and Chinese hamster cells in culture).
International Journal of Radiation Oncology*Biology*Physics, 2008
To investigate whether irradiating small lung volumes with a large dose or irradiating large lung volumes with a small dose, given the same mean lung dose (MLD), has a different effect on pulmonary function in laboratory animals. WAG/Rij/MCW male rats were exposed to single fractions of 300 kVp X-rays. Four treatments, in decreasing order of irradiated lung volume, were administered: (1) whole lung irradiation, (2) right lung irradiation, (3) left lung irradiation, and (4) irradiation of a small lung volume with four narrow beams. The irradiation times were chosen to accumulate the same MLD of 10, 12.5, or 15 Gy with each irradiated lung volume. The development of radiation-induced lung injury for < or =20 weeks was evaluated as increased breathing frequency, mortality, and histopathologic changes in the irradiated and control rats. A significant elevation of respiratory rate, which correlated with the lung volume exposed to single small doses (> or =5 Gy), but not with the MLD, was observed. The survival of the rats in the whole-lung-irradiated group was MLD dependent, with all events occurring between 4.5 and 9 weeks after irradiation. No mortality was observed in the partial-volume irradiated rats. The lung volume irradiated to small doses might be the dominant factor influencing the loss of pulmonary function in the rat model of radiation-induced lung injury. Caution should be used when new radiotherapy techniques that result in irradiation of large volumes of normal tissue are used for the treatment of lung cancer and other tumors in the thorax.
Evaluation of the Effect of Changes in Dose Rate on Rat Lung Cells
Technology in Cancer Research & Treatment, 2014
The aim of this study is to evaluate the effect of dose rate (DR) on lung tissue. The rats included in the study were randomly grouped into 3 groups: Group (G) 1 was defined as control group, and in this group rats were sham irradiated. G2 was the group receiving a single dose of 12 Gy in DR of 300 monitor unit (MU)/min. G3 was the group receiving a single dose of 12 Gy in DR of 600 MU/min. Radiotherapy (RT) was applied under general anesthesia with 6-MV photon beams to both lungs. At the 6th and 16th week of the RT, animals from each group were killed for light and electron microscopy evaluation. We evaluated the scores of each group in the 6th and the 16th week and found that in G2, there were significant increases in the perivascular fibrosis (P ¼ .018), interstitial fibrosis (P ¼ .002), total inflammation (P ¼ .040), and total fibrosis (P ¼ .003) scores. In G3, we found statistically significant increases in perivascular fibrosis (P ¼ .001), interstitial fibrosis (P ¼ .002), and total fibrosis scores (P ¼ .029). There was no significant difference in the total inflammation score in G3 (P ¼ .225). When we compare G2 and G3 in the 6th week, we found significant increase in the interstitial thickening (P ¼ .039) and total inflammation (P ¼ .035) scores in G3.Dose rate per fraction may have an impact on normal tissue toxicity. The prominent effect of increased DR in lung tissue is fibrosis which should be kept in mind, especially in cases where higher doses per fraction are used.
International Journal of Radiation Oncology*Biology*Physics, 2000
Purpose: Recent observations have shown that there are regional variations in radiation response in mouse lung as measured by functional assays. Furthermore, there are both in-field and out-of-field effects in radiationinduced lung damage as observed by DNA assay in rats. The purpose of this work is: (a) to examine mice lethality data following partial volume lung irradiation to assess the possibility of directional or regional effects, (b) to evaluate the correlation between mice lethality data and DNA damage assayed by micronuclei production in rat lung, and (c) to re-interpret mice lethality considering the existence of directional effects in lung cellular response to partial volume irradiation. Methods and Materials: The lethality data for mice, generated at the M. D. Anderson Cancer Center, Houston, and micronuclei yield data for rats obtained at Princess Margaret Hospital, Toronto, were used. A radiobiological model that allows for out-of-field and in-field effects for lung cell damage and lung response was developed. This model is based on the observation of DNA damage in shielded parts of rat lung that was assumed relevant to cell lethality and consequently overall lung response. Results: While the experimental data indicated directional or regional volume effects, the applicability of dose and volume as sole predictors of lung response to radiation was found to be unreliable for lower lung (base) irradiation in mice. This conforms well to rat lung response where micronuclei were observed in shielded apical parts of lung following base irradiation. The radiobiological model, which was specifically developed to account for the lung response outside of primary irradiated volume, provides a good fit to mice lethality data, using parameters inferred from rat micronuclei data. Conclusion: Response to lung irradiation in rodents, in particular, elevated sensitivity to base irradiation, can be interpreted with a hypothesis of in-field and out-of-field effects for cellular response. If the existence of these effects for lung is subsequently proven in humans, it will require the incorporation of geometrical and directional information in normal tissue complication probability calculations for lung. These considerations are ignored in present approaches based only on conventional dose-volume histograms. © 2000 Elsevier Science Inc.
Journal of Radiation Research, 2005
Intensity-modulated radiation therapy/Radiosurgery/Fractionation/Dose per fraction/SLDR. In intensity-modulated radiation therapy (IMRT) and stereotactic irradiation using a linear accelerator, radiation is administered intermittently and one treatment session often requires 30 min or a longer time. The purpose of the present study was to investigate the effect of fractionation and dose per fraction on cell killing by irradiation in intermittent exposure. Murine EMT6 and SCCVII cells were used. The cells were irradiated to a total dose of 8 Gy in 2, 5, 10, 20 and 40 fractions over 15, 30 and 46 min. The cells were also given 8 Gy in a single fraction over 15, 30 and 46 min using lower dose rates (continuous prolonged radiation groups). As compared with the control group receiving a single dose of 8 Gy at 1.55 Gy/min, the cell surviving fraction generally increased in groups receiving fractionated or continuous prolonged radiation. There was a general trend for cell survival to increase with the fraction number up to 20 or 40 fractions in both cell lines. The effects of IMRT and linear accelerator radiosurgery given over 15 min or longer may be less than those of 1-or 2-fraction irradiation. There was a trend for radiation effect to decrease with fraction number.