39 - Freie Mitteilung
Clinical works I
16. Mai 2019, 08:30 - 10:00, Bellavista 2, 6. OG
Evaluation of feasibility and toxicity of irradiation combined with cisplatin-fibrin administration after lung sparing surgery in an orthotopic immunocompetent rat model for malignant pleural mesothelioma
O. Lauk, M. Kirschner, M. Meerang, K. Furrer, I. Grgic, V. Orlowski, F. Tschanz, M. Pruschy, I. Opitz, Presenter: K. Furrer (Zurich)
To investigate new therapeutic treatment combinations for MPM, we performed lung-sparing surgery followed by cisplatin/fibrin application and hemithoracic irradiation in an immunocompetent rat model for malignant pleural mesothelioma (MPM).
F344 rat (n=3) were implanted sub-pleurally (parietal pleura) with 1 million rat mesothelioma cells (IL45-luciferase). Formed tumor nodules confirmed by bioluminescence (BL) were resected on day 9 after implantation. Three days later, CT-guided local irradiation of the former tumor region, resembling IMRT in human patients, was performed using an image-guided small animal radiotherapy platform (Precision X-Ray, X-Rad SmART) 225 kV unit with a dose rate of 3Gy/min with precise localization and a single high dose of 10Gy. Treatment scheme was as followed: i) Tumor resection followed by intracavitary cisplatin-fibrin application (male, n=1) ii) Tumor resection followed by 10Gy radiotherapy (male, n=1) iii) Tumor resection followed by intracavitary cisplatin-fibrin plus 10Gy radiotherapy (male, n=1).
We successfully treated 1 animal per group according to the methods above. The irradiation was performed after visualization of the tumor with BL-imaging to ensure an individual treatment plan. None of the animals, whether with radiotherapy alone or in combination with cisplatin/fibrin application, showed any signs of respiratory side effects. In addition, none had reduced pulmonary functions, measured by increased breathing or the appearance of blue or white colored ear/extremities/eyes assuming desaturation. Furthermore, neither significant body weight loss ≥ 15%, deterioration of body conditioning score nor of the activity score were observed in the immediate post-interventional phase. The survival for group i, ii and iii was 14 days, 11 days and 18 days, respectively.
Irradiation alone and in combination after cisplatin/fibrin application in rats is safe up to a dosage of 10Gy. The desired radio-sensitizing effect by intracavitary cisplatin will be further evaluated in the same animal model as already planned in a dose adjustment phase.