Pressurized intrathoracic aerosol chemotherapy (PITAC) for malignant pleural mesothelioma- ex vivo evaluation of optimal treatment conditions and comparison with hyperthermic intrathoracic chemotherapy (HITOC)

Journal of Thoracic Disease 2026 May 31 [Link]

Katharina Flöthmann, Norman Zinne, Peter Braubach, Alina Meininger, Imke Becker, Nicole Ernst, Arjang Ruhparwar, Hayan Merhej, Patrick Zardo

Abstract

Background: Malignant pleural mesothelioma (MPM) is a rare but aggressive disease with poor prognosis and limited treatment options. Pressurized intrathoracic aerosol chemotherapy (PITAC) has emerged as a novel approach for intrathoracic drug delivery. The aim of this study was to investigate cisplatin penetration characteristics and to evaluate procedural parameters influencing drug penetration, including temperature, drug concentration and pleural barrier function, in an ex vivo model. In addition, PITAC was compared with hyperthermic intrathoracic chemotherapy (HITOC), a treatment modality applied in selected specialized centers as part of multimodal treatment concepts for MPM.

Methods: We investigated the penetration depth and intensity of aerosolized cisplatin generated using a high-pressure nebulizer in an ex vivo setting. Potential influencing factors, including temperature, cisplatin concentration and barrier function of the pleura, were gradually modified, as we sought to evaluate optimal procedural conditions. Finally, PITAC was compared with a previously standardized HITOC approach.

Results: A temperature of 42 ℃, a cisplatin concentration of 1 mg/mL, and prior removal of the pleura, improved the penetration depth and intensity of the chemotherapeutic agent. Under clinically relevant experimental conditions, aerosolized cisplatin application demonstrated greater tissue penetration compared to HITOC.

Conclusions: Our preclinical data suggest that PITAC may be a viable alternative to HITOC and warrants further clinical investigation.