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    ABSTRACT: To assess the impact of increasing experience with intensity-modulated radiation therapy (IMRT) after extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM). The records of all patients who received IMRT following EPP at Duke University Medical Center between 2005 and 2010 were reviewed. Target volumes included the preoperative extent of the pleural space, chest wall incisions, involved nodal stations, and a boost to close/positive surgical margins if applicable. Patients were typically treated with 9-11 beams with gantry angles, collimator rotations, and beam apertures manually fixed to avoid the contalateral lung and to optimize target coverage. Toxicity was graded retrospectively using National Cancer Institute common toxicity criteria version 4.0. Target coverage and contralateral lung irradiation were evaluated over time by using linear regression. Local control, disease-free survival, and overall survival rates were estimated using the Kaplan-Meier method. Thirty patients received IMRT following EPP; 21 patients also received systemic chemotherapy. Median follow-up was 15 months. The median dose prescribed to the entire ipsilateral hemithorax was 45 Gy (range, 40-50.4 Gy) with a boost of 8-25 Gy in 9 patients. Median survival was 23.2 months. Two-year local control, disease-free survival, and overall survival rates were 47%, 34%, and 50%, respectively. Increasing experience planning MPM cases was associated with improved coverage of planning target volumes (P=.04). Similarly, mean lung dose (P<.01) and lung V5 (volume receiving 5 Gy or more; P<.01) values decreased with increasing experience. Lung toxicity developed after IMRT in 4 (13%) patients at a median of 2.2 months after RT (three grade 3-4 and one grade 5). Lung toxicity developed in 4 of the initial 15 patients vs none of the last 15 patients treated. With increasing experience, target volume coverage improved and dose to the contralateral lung decreased. Rates of pulmonary toxicity were relatively low. However, both local and distant control rates remained suboptimal.
    International journal of radiation oncology, biology, physics 05/2012; 83(1):362-8. DOI:10.1016/j.ijrobp.2011.11.057 · 4.26 Impact Factor
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    ABSTRACT: We report two autopsy cases of primary pulmonary adenocarcinoma associated with unusual pleural spread. Both patients had confirmed history of asbestos exposure. In the first patient the tumor was localized in one pulmonary lobe with marked infiltration into pleura, chest wall and diaphragm. In the second patient the entire right lung was covered by irregularly thickened tumor. Both tumors were mainly located in the extrapulmonary area and the intrapulmonary portions represented only minor components. Histologically, tumor cells demonstrated glandular and papillary growth patterns associated with focal hobnail-like features. Immunohistochemical evaluation revealed diffuse and marked immunoreactivity of TTF-1, CEA, CD15 and MOC31 in both cases, while calretinin, CK5/6, vimentin, thrombomodulin and HBME-1 were broadly positive in one case. D2-40 was not detected in either case. Examination using electron microscopy revealed the presence of sparse and short microvilli in tumor cells. All of the above findings are consistent with adenocarcinoma of the lung. Primary adenocarcinoma with a characteristic pleural extention grossly resembling malignant mesothelioma has been previously reported in the literature as pseudomesotheliomatous adenocarcinoma. This is the first report of pseudomesotheliomatous adenocarcinoma displaying variable immunoprofile with a diagnosis using electron microscopical examination. Additionally, we performed quantitative analysis of asbestos bodies in pseudomesotheliomatous adenocarcinoma.
    Pathology International 10/2012; 62(10-10):709-15. DOI:10.1111/j.1440-1827.2012.02860.x · 1.69 Impact Factor
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    ABSTRACT: Mesothelioma is a rare form of cancer that affects the membranous lining of the chest (pleura) and, less commonly, the lining of the abdomen and heart. The disease carries a poor prognosis and is typically associated with exposure to asbestos, a mineral that has been widely used due to its fire resistance and insulating properties. The standard non-surgical treatment for malignant pleural mesothelioma (MPM) is polychemotherapy combining cisplatin/carboplatin and a second agent with a different mechanism of action. This review outlines the use of clinically approved platinum-drugs and the design of metal-drug candidates for the treatment of MPM.
    Inorganica Chimica Acta 12/2012; 393(In Press, Corrected Proof). DOI:10.1016/j.ica.2012.06.005 · 2.05 Impact Factor
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