PurposeTo facilitate localization and resection of small lung nodules, we developed a prospective clinical trial (ClinicalTrials.gov number NCT01847209) for a novel surgical approach which combines placement of fiducials using intra‐operative C‐arm computed tomography (CT) guidance with standard thoracoscopic resection technique using image‐guided video‐assisted thoracoscopic surgery (iVATS).MethodsPretrial training was performed in a porcine model using C‐arm CT and needle guidance software. Methodology and workflow for iVATS was developed, and a multi‐modality team was trained. A prospective phase I‐II clinical trial was initiated with the goal of recruiting eligible patients with small peripheral pulmonary nodules. Intra‐operative C‐arm CT scan was utilized for guidance of percutaneous marking with two T‐bars (Kimberly‐Clark, Roswell, GA) followed by VATS resection of the tumor.ResultsTwenty‐five patients were enrolled; 23 underwent iVATS, one withdrew, and one lesion resolved. Size of lesions were: 0.6–1.8 cm, mean = 1.3 ± 0.38 cm.. All 23 patients underwent complete resection of their lesions. CT imaging of the resected specimens confirmed the removal of the T‐bars and the nodule. Average and total procedure radiation dose was in the acceptable low range (median = 1501 μGy*m2, range 665–16,326). There were no deaths, and all patients were discharged from the hospital (median length of stay = 4 days, range 2–12). Three patients had postoperative complications: one prolonged air‐leak, one pneumonia, and one ileus.ConclusionsA successful and safe step‐wise process has been established for iVATS, combining intra‐operative C‐arm CT scanning and thoracoscopic surgery in a hybrid operating room. J. Surg. Oncol. 2015 111:18–25. © 2015 The Authors. Journal of Surgical Oncology Published by Wiley Periodicals, Inc.

PD-L1 immunohistochemical staining does not always predict whether a cancer will respond to treatment with PD-1 inhibitors. We sought to characterize immune cell infiltrates and the expression of T-cell inhibitor markers in PD-L1-positive and PD-L1-negative malignant pleural mesothelioma samples. We developed a method for immune cell phenotyping using flow cytometry on solid tumors that have been dissociated into single-cell suspensions and applied this technique to analyze 43 resected malignant pleural mesothelioma specimens. Compared with PD-L1-negative tumors, PD-L1-positive tumors had significantly more infiltrating CD45 immune cells, a significantly higher proportion of infiltrating CD3 T cells, and a significantly higher percentage of CD3 cells displaying the activated HLA-DR/CD38 phenotype. PD-L1-positive tumors also had a significantly higher proportion of proliferating CD8 T cells, a higher fraction of FOXP3/CD4 Tregs, and increased expression of PD-1 and TIM-3 on CD4 and CD8 T cells. Double-positive PD-1/TIM-3 CD8 T cells were more commonly found on PD-L1-positive tumors. Compared with epithelioid tumors, sarcomatoid and biphasic mesothelioma samples were significantly more likely to be PD-L1 positive and showed more infiltration with CD3 T cells and PD-1/TIM-3 CD8 T cells. Immunologic phenotypes in mesothelioma differ based on PD-L1 status and histologic subtype. Successful incorporation of comprehensive immune profiling by flow cytometry into prospective clinical trials could refine our ability to predict which patients will respond to specific immune checkpoint blockade strategies. Cancer Immunol Res; 4(12); 1038-48. ©2016 AACR.

Objective: We developed a novel approach for localization and resection of lung nodules, using image-guided video-assisted thoracoscopic surgery (iVATS). We report our experience of translating iVATS into clinical care.Methods: Methodology and workflow for iVATS developed as part of the Phase I/II trial were used to train surgeons, radiologists, anesthesiologists, and radiology technologists. Radiation dose, time from induction to incision, placement of T-bar to incision and incision to closure, hospital stay, and complication rates were recorded.Results: Fifty patients underwent iVATS for resection of 54 nodules in a clinical hybrid operating room (OR) by six surgeons. Fifty-two (97%) nodules were successfully resected.Forty-two (84%) patients underwent wedge resection, four (7%) lobectomies, and two (4%) segmentectomy all with lymph node dissection. Median time from induction to incision was 89 minutes (range: 13-256 minutes); T-bar placement was 14 minutes (10-29 minutes); and incision to closure, 107 minutes (41-302 minutes). Average and total procedure radiation dose were: median = 6 mSieverts (range: 2.9-35 mSieverts). No deaths were reported and median length of stay was 3 days (range: 1-12 days).Conclusions: Translation of iVATS into clinical practice has been initiated using a safe step-wise process, combining intraoperative C-arm computed tomography scanning and thoracoscopic surgery in a hybrid OR. K E Y W O R D Sadvanced image-guided operating room, C-arm CT, fiducials, hybrid operating room, lung cancer, VATS