Intracavitary cisplatin-fibrin followed by irradiation improved tumor control compared to the single treatments in a mesothelioma rat modelCentral MessagePerspective
Michaela B. Kirschner, PhD,
Mayura Meerang, PhD,
Vanessa Orlowski,
Katarzyna Furrer, MD,
Fabienne Tschanz, PhD,
Ivo Grgic, PhD,
Virginia Cecconi, PhD,
Maries van den Broek, PhD,
Matthias Guckenberger, MD,
Martin Pruschy, MD,
Olivia Lauk, MD,
Isabelle Opitz, MD
Affiliations
Michaela B. Kirschner, PhD
Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
Mayura Meerang, PhD
Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
Vanessa Orlowski
Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
Katarzyna Furrer, MD
Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
Fabienne Tschanz, PhD
Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland
Ivo Grgic, PhD
Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland
Virginia Cecconi, PhD
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland
Maries van den Broek, PhD
Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland
Matthias Guckenberger, MD
Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland
Martin Pruschy, MD
Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland
Olivia Lauk, MD
Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
Isabelle Opitz, MD
Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland; Address for reprints: Isabelle Opitz, MD, Department of Thoracic Surgery, University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.
Objective: To test the safety and efficacy of combination treatment for pleural mesothelioma (PM) with intracavitary cisplatin-fibrin (cis-fib) plus hemithoracic irradiation (IR) applied after lung-sparing surgery in an orthotopic immunocompetent rat model. Methods: We randomized male F344 rats into 5 groups: cis-fib (n = 9), 10 Gy IR (n = 6), 20 Gy IR (n = 9), cis-fib+10 Gy IR (n = 6), and cis-fib+20 Gy IR (n = 9). Subpleural tumor implantation was performed on day 0 with 1 million syngeneic rat mesothelioma cells (IL45-luciferase). Tumors were resected on day 9, followed by treatment with intracavitary cis-fib or vehicle control (NaCl-fib). On day 12, computed tomography–guided local irradiation in a single high dose of the former tumor region was applied. Results: We observed only short-term side effects related to 20 Gy radiotherapy. Compared to 20 Gy, 10 Gy IR did not show an impact on tumor growth. At 3 days after treatment with 20 Gy IR (day 15 of the experiment), we detected significantly smaller tumors in the cis-fib+IR group compared to IR alone (mean tumor growth, 252% vs 539%; P = .04). On day 21, there was a significant difference in tumor growth between cis-fib–treated and cis-fib+IR– treated tumors (mean tumor growth, 2295% vs 660%; P = .01). Conclusions: Localized treatment after tumor resection in PM aims to improve local tumor control. Irradiation applied in combination with intracavitary cis-fib in rats is safe up to a dosage of 20 Gy and shows an additive effect on tumor growth delay compared to the single treatments.
