105. Patient Derived Xenograft Engraftment of Lung Adenocarcinoma is Associated with Preoperative Radiological Findings
Presented During: Translational Research for the Near Future
University of California San Diego
La Jolla, CA
United States - Contact Me
Mark Onaitis is Professor of Surgery and the Sheri Kelts Chair in Cardiothoracic Surgery at the University of California, San Diego.
Latner Thoracic Research Laboratories, University Health Network
Toronto, ON
Canada - Contact Me
Dr. Ogawa is a Thoracic Surgeon from Japan who graduated from Kobe University School of Medicine in 2008. He researched lung cancer stem cells at the department of iPS cell application at Kobe University from 2013 to 2017. He is currently working on the clinical application of lung cancer organoid model.
Sunday, May 7, 2023: 8:15 AM - 8:30 AM
Los Angeles Convention Center
Room: 408B
Abstract
Objective: Patient derived xenografts (PDXs) are patient tumors engrafted into immunodeficient mice. PDXs are useful for preclinical drug efficacy studies as they preserve many molecular and histological features of patient tumors. However, the engraftment rates of lung adenocarcinoma range from 20-40%, and this low engraftment rate limits the utility of PDX as models of clinical cancer.
Strong associations between CT imaging of lung nodules such as solid, part-solid, and ground grass opacity (GGO) and patient prognosis has been reported for non-small cell lung cancer (NSCLC). We hypothesized that radiological findings may predict PDX engraftments.
Methods: Fresh tumor tissues from surgical resections were implanted and grown in the subcutaneous pocket of NOD SCID gamma (NSG) mice; subsequent passages were grown in NOD SCID mice. FDG-PET and CT images were reviewed. The pulmonary nodules were classified into three categories such as solid / part-solid / GGO nodules. The data on total tumor size, solid tumor size, consolidation-tumor ratio (CTR), and maximum standardized uptake value (SUV max) were obtained from patient clinical records. We evaluated whether these radiological findings correlated with the PDXs engraftment.
Results: A total of 254 resected primary lung adenocarcinomas were implanted into NSG mice between 2006 and 2012. Engraftment was successful in 58 cases (22.8%). Among them, stable engraftment, which could be passaged serially at least 3 times was observed in 43 cases (16.9%), and unstable engraftment, which could not be passaged ≥3 times was observed in 15 cases (5.9%). There were 190 (74.8%) solid, 62 (24.4%) part-solid, and 2 (0.8%) GGO nodules. Stable engraftment rates from solid, part-solid, and GGO nodules were 22.1% (42 /190 cases), 1.6% (1 /62 cases), and 0% (0 /2 cases), respectively (Figure A). Tumor size (total and solid tumor size), CTR and SUVmax were also strongly associated with the PDXs stable engraftment (Figure B-E).
Conclusions: Large solid lung adenocarcinomas with high CTR and high SUVmax were more strongly associated with stable PDX engraftment. It may be cost-effective to avoid part-solid and GGO nodules for establishing PDXs in lung adenocarcinoma cases due to the low engraftment rate.
Strong associations between CT imaging of lung nodules such as solid, part-solid, and ground grass opacity (GGO) and patient prognosis has been reported for non-small cell lung cancer (NSCLC). We hypothesized that radiological findings may predict PDX engraftments.
Methods: Fresh tumor tissues from surgical resections were implanted and grown in the subcutaneous pocket of NOD SCID gamma (NSG) mice; subsequent passages were grown in NOD SCID mice. FDG-PET and CT images were reviewed. The pulmonary nodules were classified into three categories such as solid / part-solid / GGO nodules. The data on total tumor size, solid tumor size, consolidation-tumor ratio (CTR), and maximum standardized uptake value (SUV max) were obtained from patient clinical records. We evaluated whether these radiological findings correlated with the PDXs engraftment.
Results: A total of 254 resected primary lung adenocarcinomas were implanted into NSG mice between 2006 and 2012. Engraftment was successful in 58 cases (22.8%). Among them, stable engraftment, which could be passaged serially at least 3 times was observed in 43 cases (16.9%), and unstable engraftment, which could not be passaged ≥3 times was observed in 15 cases (5.9%). There were 190 (74.8%) solid, 62 (24.4%) part-solid, and 2 (0.8%) GGO nodules. Stable engraftment rates from solid, part-solid, and GGO nodules were 22.1% (42 /190 cases), 1.6% (1 /62 cases), and 0% (0 /2 cases), respectively (Figure A). Tumor size (total and solid tumor size), CTR and SUVmax were also strongly associated with the PDXs stable engraftment (Figure B-E).
Conclusions: Large solid lung adenocarcinomas with high CTR and high SUVmax were more strongly associated with stable PDX engraftment. It may be cost-effective to avoid part-solid and GGO nodules for establishing PDXs in lung adenocarcinoma cases due to the low engraftment rate.
Presentation Duration
7 minute presentation; 7 minute discussion