Lasers in Surgery and Medicine 47:807–816 (2015) Treatment of Pleural Malignancies by Photo-Induction Combined to Systemic Chemotherapy: Proof of Concept on Rodent Lung Tumors and Feasibility Study on Porcine Chest Cavities Xingyu Wang, 1 Fabrizio Gronchi, 2 Michael Bensimon, 3 Thomas Mercier, 4 Laurent Arthur Decosterd, 4 Georges Wagni eres, 3 Elodie Debefve, 1 Hans-Beat Ris, 1Ã Igor Letovanec, 5 Solange Peters, 6 and Jean Yannis Perentes 1 1 Departement of Thoracic Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, VD, Switzerland 2 Department of Anesthesiology, Centre Hospitalier Universitaire Vaudois, Lausanne, VD, Switzerland 3 Central Environmental Laboratory, Swiss Federal Institute of Technology(EPFL), Lausanne, VD, Switzerland 4 Departement of Pharmacology, Centre Hospitalier Universitaire Vaudois, Lausanne, VD, Switzerland 5 Department of Pathology, University of Lausanne, Lausanne, VD, Switzerland 6 Departement of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, VD, Switzerland Background: Low-dose, Visudyne 1 -mediated photody- namic therapy (photo-induction) was shown to selectively enhance tumor vessel transport causing increased uptake of systemically administered chemotherapy in various tumor types grown on rodent lungs. The present experi- ments explore the efficacy of photo-induced vessel modu- lation combined to intravenous (IV) liposomal cisplatin (Lipoplatin 1 ) on rodent lung tumors and the feasibility/ toxicity of this approach in porcine chest cavities. Material and Methods: Three groups of Fischer rats underwent orthotopic sarcoma (n ¼ 14), mesothelioma (n ¼ 14), or adenocarcinoma (n ¼ 12) implantation on the left lung. Half of the animals of each group had photo- induction (0.0625 mg/kg Visudyne 1 , 10 J/cm 2 ) followed by IV administration of Lipoplatin 1 (5 mg/kg) and the other half received Lipoplatin 1 without photo-induction. Then, two groups of minipigs underwent intrapleural thoraco- scopic (VATS) photo-induction (0.0625 mg/kg Visudyne 1 ; 30 J/cm 2 hilum; 10 J/cm 2 apex/diaphragm) with in situ light dosimetry in combination with IV Lipoplatin 1 administration (5 mg/kg). Protocol I (n ¼ 6) received Lip- oplatin 1 immediately after light delivery and Protocol II (n ¼ 9) 90 minutes before light delivery. Three additional animals received Lipoplatin 1 and VATS pleural biopsies but no photo-induction (controls). Lipoplatin 1 concentra- tions were analyzed in blood and tissues before and at regular intervals after photo-induction using inductively coupled plasma mass spectrometry. Results: Photo-induction selectively increased Lipopla- tin 1 uptake in all orthotopic tumors. It significantly increased the ratio of tumor to lung Lipoplatin 1 concen- tration in sarcoma (P ¼ 0.0008) and adenocarcinoma (P ¼ 0.01) but not in mesothelioma, compared to IV drug application alone. In minipigs, intrapleural photo-induc- tion combined to systemic Lipoplatin 1 was well tolerated with no toxicity at 7 days for both treatment protocols. The pleural Lipoplatin 1 concentrations were not significantly different at 10 and 30 J/cm 2 locations but they were significantly higher in protocol I compared to II (2.37 Æ 0.7 vs. 1.37 Æ 0.7 ng/mg, P < 0.001). Conclusion: Visudyne 1 -mediated photo-induction selec- tively enhances the uptake of IV administered Lipoplatin 1 in rodent lung tumors. Intrapleural VATS photo-induction with identical treatment conditions combined to IV Lip- oplatin chemotherapy is feasible and well tolerated in a porcine model. Lasers Surg. Med. 47:807–816, 2015. ß 2015 Wiley Periodicals, Inc. Key words: adenocarcinoma; mesothelioma; sarcoma; rodent; minipig; lung; lipoplatin; chemotherapy; photo- dynamic therapy; visudyne INTRODUCTION Malignant pleural disease is a frequently observed clinical entity that has an important social, medical, and economic burden [1]. Current treatment is based on systemic cisplatin-based chemotherapy but success is limited due, in part, to the poor penetration of cytostatic agents into tumors. Recently, several studies have shown Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Xingyu Wang, Fabrizio Gronchi, Solange Peters, and Jean Yannis Perentes contributed to this work equally. Contract grant sponsor: Swiss National Foundation; Contract grant numbers: 3200030, 135197. Ã Correspondance to: Hans-Beat Ris, MD, Service de chirurgie thoracique, CHUV, rue du Bugnon 21, 1011 Lausanne. E-mail: hans-beat.ris@chuv.ch Accepted 13 September 2015 Published online 28 September 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/lsm.22422 ß 2015 Wiley Periodicals, Inc.