Abstract 1056: Cancer avatars are sensitive diagnosticians of the pleural space

The identification of malignant cells in pleural fluid has critical prognostic and therapeutic implications but is frequently a diagnostic challenge. The first step in determining the cause of a suspected malignant pleural effusion, thoracentesis, has an unsatisfying low sensitivity (~60-70%). Patient-derived xenografts (PDX) retain the principal characteristics of the tumor of origin. However, there has been little progress in the application of these models to guide diagnostic and staging strategies. We assessed the feasibility, cellular yield and comparative diagnostic accuracy of pleural-derived xenografts in patients with effusions. An institutional review board-approved single-institution prospective registry of patients was used to identify patients undergoing diagnostic and/or therapeutic thoracentesis. Cells isolated from the pleural fluid of these patients were injected into NSG mice. A diagnosis of the cancer in the xenograft was confirmed by a staff pathologist with expertise in the correspondent cancer type. All of the cases that were clinically positive for tumor cells in the pleural space demonstrated tumor engraftment. Samples taken from patients with known benign etiologies did not result in tumor engraftment. The developed xenografts provided ample tissue that can be made available for extensive molecular testing, even in cases where the cytological samples consisted of very few cells. Critically, two of 10 cases resulted in engraftment of the tumor despite no evidence of malignant cells on cytological examination, indicating a 20% improvement in the statistical power of pleural-based xenografting for the detection of malignancy. Our study indicates that pleural-derived xenografts can enhance the sensitivity of malignant cell detection, reflecting the inherent limitations of cytological analyses of a few malignant cells. Moreover, the amplification of cellular material provides ample source material that can be used to satisfy the increasing demands for tissue-based molecular testing. To our knowledge, this is the first effort to effectively use patient-derived xenografts for the purpose of cancer staging and diagnosis. Citation Format: Gwendolyn B. Kuzmishin, Priyanka Gopal, Mohamed E. Abazeed. Cancer avatars are sensitive diagnosticians of the pleural space [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1056.