Sebastian Bickelhaupt, Presenter: Nothing to Disclose

Peter Peschke PhD, Abstract Co-Author: Nothing to Disclose

Juergen Debus MD, PhD, Abstract Co-Author: Nothing to Disclose

Peter Ernst Huber MD, PhD, Abstract Co-Author: Nothing to Disclose

Particle radiotherapy including Carbon ion irradiation is of increasing interest for tumor treatments yet its side effects are barely investigated, especially for radiosensitive organs such as the lung. We investigated the pulmonary toxicity of carbon ion irradiation in mice lungs and the correlation of computed tomography imaging in correlation to the Radiation Therapy Oncology Group (RTOG) scores and histopathology.

All animal procedures were IRB/GRB approved. Thoraces of female C57BL/6 mice were irradiated with a single dose of 11Gy Carbon ions (C12) , non-irradiated animals served as controls. Computed tomography monitoring using a SOMATOM multi-slice CT scanner(Siemens) (120kV,100mAS,whole thoracic,0.5-mm slice-thickness, acquisition time 0.5 s) was performed every 2/4 weeks in a longitudinal manner until week 24. Hounsfield Units (HU) with 3D-intrapulmonal homogeneity analyses and pulmonary changes according to the radiological RTOG (Radiation Therapy Oncology Group) scores were measured and correlated. Further lung histology and morphometric analyses were performed and integrated into the analysis. Statistics were calculated using Student´s-t-test, Spearmans correlation coefficient and log-rank tests.

Lung density in mice progressively increased after 12 weeks until 22 weeks after irradiation from about -480 HU (SEM+-4.25) to -300 HU (SEM+-26.0) in a homogenous pattern with no significant (p>0.05) difference between the intrapulmonal lung regions. Similarly RTOG scores increased from mean 0 to 2.96 (SEM+-0.25) in week 22, both measurement tools indicated significant (p<0.05) pulmonary changes to controls 16 weeks after irradiation. A high correlation was found between the RTOG Scores and the HU measurements (p=0.0046, r=-0.89). All findings showed a high correlation to the histopathological examinations presenting lung remodeling indicative of fibrosis that was lethal in all irradiated animals at week 24.

Carbon ion irradiation induced lethal pulmonary toxicity in a homogenous pattern with computed tomography monitoring showing a high correlation between the Hounsfield Units increase and the RTOG scores. Both methods seem appropriate for monitoring carbon ion radiotherapy induced pulmonary toxicity.

Hounsfield values and the RTOG scores are a valuable tool for preclinical studies as a translational approach in monitoring pulmonary toxicity after irradiation.

Bickelhaupt, S, Peschke, P, Debus, J, Huber, P, Longitudinal Computed Tomography Monitoring of Carbon-Ion Radiation Induced Pulmonary Fibrosis in Mice in Correlation to the Radiation Therapy Oncology Group (RTOG) Classification.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14002862.html