Patient Derived Xenograft Engraftment of Lung Adenocarcinoma is Associated with Preoperative Radiological Findings.

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Abstract Submission 

Hiroyuki Ogawa (1), Takamasa Koga (1), Nicholas Bernards (1), Alexander Gregor (1), Yuki Sata (1), Shinsuke Kitazawa (1), Yoshihisa Hiraishi (1), Tsukasa Ishiwata (1), Masato Aragaki (1), Fumi Yokote (1), Andrew Effat (1), Kate Kazlovich (1), Nhu-An Pham (2), Ming-Sound Tsao (2), Kazuhiro Yasufuku (1)

(1) Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, (2) Princess Margaret Cancer Center, University Health Network, Toronto, Ontario

Hiroyuki Ogawa    -  Contact Me
Division of Thoracic Surgery, Toronto General Hospital, University Health Network

Takamasa Koga    -  Contact Me
Division of Thoracic Surgery, Toronto General Hospital, University Health Network

Nicholas Bernards    -  Contact Me
Division of Thoracic Surgery, Toronto General Hospital, University Health Network

Alexander Gregor    -  Contact Me
Division of Thoracic Surgery, Toronto General Hospital, University Health Network

Yuki Sata    -  Contact Me
Division of Thoracic Surgery, Toronto General Hospital, University Health Network

Shinsuke Kitazawa    -  Contact Me
Division of Thoracic Surgery, Toronto General Hospital, University Health Network

Yoshihisa Hiraishi    -  Contact Me
Division of Thoracic Surgery, Toronto General Hospital, University Health Network

Tsukasa Ishiwata    -  Contact Me
Division of Thoracic Surgery, Toronto General Hospital, University Health Network

Masato Aragaki    -  Contact Me
Division of Thoracic Surgery, Toronto General Hospital, University Health Network

Fumi Yokote    -  Contact Me
Division of Thoracic Surgery, Toronto General Hospital, University Health Network

Andrew Effat    -  Contact Me
Division of Thoracic Surgery, Toronto General Hospital, University Health Network

Kate Kazlovich    -  Contact Me
Division of Thoracic Surgery, Toronto General Hospital, University Health Network

Nhu-An Pham    -  Contact Me
Princess Margaret Cancer Center, University Health Network

Ming-Sound Tsao    -  Contact Me
Princess Margaret Cancer Center, University Health Network

*Kazuhiro Yasufuku    -  Contact Me
Division of Thoracic Surgery, Toronto General Hospital, University Health Network

Hiroyuki Ogawa    -  Contact Me
Latner Thoracic Research Laboratories, university health network

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.

Basic and Translational Research