Background Radical pleurectomy (RP) for mesothelioma is often considered either technically infeasible or an operation limited to patients who would not tolerate a pneumonectomy. The purpose of this study was to review our experience using RP and intraoperative photodynamic therapy (PDT) for mesothelioma. Methods 38 patients (42–81 years) underwent RP-PDT. 35/38 (92%) patients also received systemic therapy. Standard statistical techniques were employed for analysis. Results 37/38 (97%) patients had Stage III/IV (AJCC) cancer and 7/38 (18%) patients had nonepithelial subtypes. Macroscopic complete resection was achieved in 37/38 (97%) patients. There was one postoperative mortality (stroke). At a median follow-up of 34.4 months, the median survival was 31.7 months for all 38 patients, 41.2 months for the 31/38 (82%) epithelial patients and 6.8 months for the 7/38 (18%) nonepithelial patients. The median progression free survivals were 9.6, 15.1 and 4.8 months, respectively. The median and progression free survivals for the 20/31 (64%) epithelial patients with N2 disease were 31.7 and 15.1 months, respectively. Conclusions It was possible to achieve a macroscopic complete resection utilizing lung-sparing surgery in 97% of these stage III/IV patients. The survival we observed with this approach was unusually long for the epithelial subtype patients but, interestingly, the progression free survival was not. The reason for this prolonged survival in spite of recurrence is not clear, but is potentially related to preservation of the lung and/or some PDT-induced effect. We conclude that the results of this lung-sparing approach are safe, encouraging and warrant further investigation.

Background The purpose of this study was to assess survival for patients with malignant pleural mesothelioma (MPM), epithelial subtype, utilizing extended pleurectomy-decortication combined with intraoperative photodynamic therapy (PDT) and adjuvant pemetrexed-based chemotherapy. Methods From 2005 to 2013, 90 patients underwent lung-sparing surgery and PDT for MPM. All patients had a preoperative diagnosis of epithelial subtype, of which 17 proved to have mixed histology. The remaining 73 patients with pure epithelial subtype are analyzed. All patients received lung-sparing surgery and PDT. 92% also received chemotherapy. The median follow up was 5.3 years for living patients. Results Macroscopic complete resection was achieved in all 73 patients. 30 and 90 day mortalities were 3% and 4%, respectively. For all 73 patients (89% AJCC Stage III/IV, 69% N2 disease and median tumor volume 550 ml) the median overall and disease free survivals were 3 years and 1.2 years, respectively. For the 19 patients without lymph node metastases (74% Stage III/IV, median tumor volume 325 ml) the median overall and disease free survivals were 7.3 years and 2.3 years, respectively. Conclusions This is a mature data set for MPM that demonstrates the ability to safely execute a complex treatment plan that included a surgical technique that consistently permitted achieving a macroscopic complete resection while preserving the lung. The role for lung-sparing surgery is unclear but this series demonstrates that it is an option, even in advanced cases. The overall survival of 7.3 years for the node negative subset of patients, still of advanced stage, is encouraging. Of particular interest is the overall survival being approximately triple the disease free survival, perhaps PDT-related. The impact of PDT is unclear, but hopefully will be established by an ongoing randomized trial.

New therapeutic strategies are needed for malignant pleural mesothelioma (MPM). We conducted a single-center, open-label, nonrandomized, pilot and feasibility trial using two intrapleural doses of an adenoviral vector encoding human IFN-a (Ad.IFN-a2b). Nine subjects were enrolled at two dose levels. The first three subjects had very high pleural and systemic IFN-a concentrations resulting in severe "flu-like" symptoms necessitating dose de-escalation. The next six patients had reduced (but still significant) pleural and serum IFN-a levels, but with tolerable symptoms. Repeated vector administration appeared to prolong IFN-a expression levels. Antitumor humoral immune responses against mesothelioma cell lines were seen in seven of the eight subjects evaluated. No clinical responses were seen in the four subjects with advanced disease. However, evidence of disease stability or tumor regression was seen in the remaining five patients, including one dramatic example of partial tumor regression at sites not in contiguity with vector infusion. These data show that Ad.IFN-a2b has potential therapeutic benefit in MPM and that it generates anti-tumor immune responses that may induce anatomic and/or metabolic reductions in distant tumor. Clinical trial registered with www.clinicaltrials.gov (NCT 01212367).

Our results indicate surgery and PDT can be performed safely with very good local control. The median survival of 21.7 months, calculated from the time of surgery and PDT is encouraging. Further evaluation of this therapy is warranted.