A Novel Prospective Study Assessing the Combination of Photodynamic Therapy and Proton Radiation Therapy: Safety and Outcomes When Treating Malignant Pleural Mesothelioma

Malignant pleural mesothelioma remains difficult to treat, with high failure rates despite optimal therapy. We present a novel prospective trial combining proton therapy ( PT ) and photodynamic therapy ( PDT ) and the largest‐ever mesothelioma PT experience ( n  =   10). PDT photosensitizers included porfimer sodium (2 mg·kg −1 ; 24 h drug‐light interval) or 2‐[1‐hexyloxyethyl]‐2‐devinyl pyropheophorbide‐a ( HPPH ) (4 mg·m −2 ;48 h) with wavelengths of 630 nm to 60J·cm −2 and 665 nm to 15‐45J·cm −2 , respectively. With a median age of 69 years, patients were predominantly male (90%) with epithelioid histology (100%) and stage III ‐ IV disease (100%). PT was delivered to a median of 55.0 CGE /1.8‐2.0 CGE (range 50–75 CGE ) adjuvantly ( n  =   8) or as salvage therapy ( n  =   2) following extended pleurectomy/decortication ( ePD )/ PDT . Two‐year local control was 90%, with distant and regional failure rates of 50% and 30%, respectively. All patients received chemotherapy, and four received immunotherapy. Surgical complications included atrial fibrillation ( n  =   3), pneumonia ( n  =   2), and deep vein thrombosis ( n  =   2). Median survival from PT completion was 19.5 months (30.3 months from diagnosis), and 1‐ and 2‐year survival rates were 58% and 29%. No patient experienced CTCAE v4 grade ≥2 acute or late toxicity. Our prolonged survival in very advanced‐stage patients compares favorably to survival for PT without PDT and photon therapy with PDT , suggesting possible spatial or systemic cooperativity and immune effect.