Response of pig lung to irradiation with accelerated 12 C-ions

Abstract

The response of pig lungs to irradiation with 12C-ions was assessed in two experiments to validate the procedures for heavy ion therapy planning at the Gesellschaft für Schwerionenforschung (GSI) and to explore their range of applicability. In both experiments, the target volume (spread-out Bragg peak, SOBP) was planned to be a 4 cm long cylinder with a diameter of 4 cm. Doses in the SOBP were prescribed to be equivalent to 5x4 Gy, 5x5.5 Gy and 5x7 Gy of x-rays in the first experiment, and to 5 fractions of 7 Gy and 9 Gy in the second experiment. The lung response in the first experiment was less than expected on the basis of earlier experiments with photons. Pneumonitis reaction and chronic fibrotic changes were observed outside the prescribed high-dose region. In the second experiment, the effects were more pronounced than had been expected on the basis of the first experiment. Changes were most intense in the high-dose region, but were also seen throughout the lung along the beam channel. Moreover, significant skin reactions were observed at the beam entrance site in all animals and - less pronounced - at the beam exit site in 3 of the 6 animals. In conclusion, the complex irradiation geometry of the pig lung, the changes of body weight between the two experiments, and insufficient accounting for a change in the relative biological effectiveness (RBE) computation led to substantial deviations of the observed reactions from expectations, the reasons for which could be identified in a subsequent analysis. The less pronounced lung reaction in the first experiment was due to an overestimation of RBE in a preliminary version of the algorithm for its determination. The extension of the fibrotic reaction resulted from the smear-out of the high-dose region due to density variations in tissue structures, respiratory movement, and limited positioning accuracy. The skin reactions at the entrance port reflect the different treatment geometry in the two experiments. The one unexplained observation is the mild skin reaction that was observed in the second experiment at the beam exit site.

Rapid calculation of biological effects in ion radiotherapy

“…Endpoints are cell survival (CHO), erythema (skin), late effects (pig lung) and tumour control (chordoma), respectively. Experiments with cell cultures as well as clinical experience have shown that the ion radiation response of these tissues, in vitro and in vivo, is in good or at least reasonable agreement with the classical model predictions (Schulz-Ertner et al 2004, Krämer et al 2003, Dörr et al 1999, Zacharias et al 1997. The deviations between classical and low-dose method are below 5% for all four tissues at therapeutical doses of up to 10 GyE per fraction.…”

“…lung) indicate a steep decrease of f with decreasing particle energy. The other radiobiological parameters listed in table 1 are those used for the experimental design and verification of in vivo skin and lung irradiation (Dörr et al 1999, Zacharias et al 1997 and in vitro irradiation of CHO-K1 cells (Krämer et al 2003). Parameters for chordoma are estimated based on the tumour growth characteristics according to the clinical data reported by Battermann et al (1981).…”

LGM2605 Reduces Space Radiation-Induced NLRP3 Inflammasome Activation and Damage in In Vitro Lung Vascular Networks

“…Little is known about the lung’s response to GCR and SPE exposures whose high linear energy transfer (LET) components penetrate deeply into exposed tissues and produce secondary radiations. There are important, but limited, studies addressing radiation to the lung [63,72,73,74,75,76]. In contrast, there are extensive studies on the effects of high-dose terrestrial, low LET radiation such as gamma- and X-rays on various tissues, including the lung.…”

RBE and related modeling in carbon-ion therapy

“…Although quite a large number of RBE measurements have been performed in vivo, only a very few dedicated experiments have been performed to benchmark predictions of clinically applied RBE models. The first in vivo experiment to validate the procedures for carbon ion treatment planning at the Helmholtz Centre for Heavy Ion Research (GSI) in pig lungs as a model for normal tissue effects revealed the problems associated with dose planning when complex moving structures are included in the beam channel (Dörr et al 1999).…”