P70.04 Results From a Patient Avatar Program Utilizing Murine Xenografts and Organoids After Neoadjuvant Therapy for Operable NSCLC

Abstract

Patient-derived xenografts (PDX) and organoids (PDO) are well described methods of propagating patient tumors. While propagation of such models are well established in treatment naïve patients after surgical resection, little is known of the prognostic utility of such methods in the context of patients who have undergone neoadjuvant therapy with conventional therapy (chemotherapy +/- radiation), immune checkpoint blockade (ICB) or tyrosine kinase inhibitor (TKI) for patients with operable non-small cell lung cancer (NSCLC). This study aims to evaluate PDX and PDO propagation rates after surgical resection from patients treated with a variety of conventional and emerging ICB neoadjuvant treatment regimens, as well as correlation with extent of pathological response. All trials of PDX and PDO implantation performed at the McGill University, Goodman Cancer Research Centre since 2017 from samples of lung cancer patients treated at the Montreal General Hospital were reviewed. After intraoperative specimen evaluation by a clinical pathologist, tumor pieces of 5 mm3 were taken for live banking PDX and PDO procedures. A retrospective chart review was then performed to obtain patient demographic and treatment data. A total of 80 PDX implantation and 28 PDO culture trials were performed, with respective take rates of 25% and 82%. Overall, 35/80 PDX trials (20 chemotherapy only, 2 chemotherapy +/- ICB, 2 chemoradiation, 10 ICB, and 1 TKI) and 23/28 PDO trials (11 chemotherapy only, 3 chemotherapy +/- ICB, 1 chemoradiation, 7 ICB, and 1 TKI) were from patients who received neoadjuvant treatment. In these patients, our take rates were 17% for PDX and 78% for PDO. 5 neoadjuvant-treated patients had a major pathological response (MPR) and 2 patients, a pathological complete response (pCR). Of those with MPR, 1/5 sample was successfully propagated in PDXs, and another 1/5 sample failed to propagate in PDXs, but grew organoids. Interestingly, 0/10 patients who received neoadjuvant ICB grew in PDXs versus 3/10 where PDOs were successfully propagated. PDX and PDO models offer tangible opportunities to create living patient avatars. Our study suggests that PDX and PDO propagation is possible after a variety of neoadjuvant treatment regimens, though we were unable to propagate PDX from ICB-treated patients. Furthermore, MPR did not preclude subsequent tumor propagation in PDX or PDO. The clinical relevance of these findings and biology underlying our findings remains to be further explored.