Abstract 1741P
Background
The feasibility of tumor-derived lung cancer organoid (LCO) for therapeutic screening has been documented. Studies demonstrating the feasibility of LCO established from malignant effusion are limited. In this study, we investigated the potential of effusion for establishing LCO and the potential of LCO for therapeutic screening.
Methods
Malignant effusion specimens, obtained from 25 patients with metastatic non-small cell lung cancer (NSCLC), were processed for establishing LCO culture. Capture-based targeted sequencing was performed on LCOs and matched effusion samples. The response to osimertinib was preliminarily assessed on LCOs and in NSCLC patients.
Results
EGFR, TP53 and RB1 were the most frequently mutated genes in LCOs and effusion samples. LCOs had a comparable median maximum somatic allele frequency with matched effusion. Eleven matched LCOs and effusion samples had available tumor mutation burden (TMB). The comparable TMB was observed between LCO and effusion. Moreover, the positive correlation between LCO based-TMB and effusion based-TMB was observed. Next, the concordance of somatic alterations between LCO and matched effusion samples was analyzed. The by-variant sensitivity for all somatic alterations in LCOs was 70.1% with a specificity of 97.7%, when effusion samples served as a reference. Furthermore, the by-variant sensitivity for actionable alterations in LCOs achieved 82.1% with a specificity of 98.0%. Three patients achieved partial response to osimertinib and their matched LCOs were also sensitive to osimertinib. One patient achieved stable disease and the matched LCO was not sensitive to osimertinib. For another three patients with the best response of progressive disease to osimertinib, two matched LCO samples were refractory while the other was sensitive to osimertinib. Our work suggested that the response of cells from LCO to osimertinib might reflect the efficacy of osimertinib in a real-world cohort of patients.
Conclusions
Our study showed the establishment of LCO from effusion specimens was feasible and the malignant effusion-derived LCO might serve as an in vitro cancer model for therapeutic screening.
Clinical trial identification
Editorial acknowledgement
Hai-Wei Du, Jian-Xing Xiang, Lu-Ting Qiu, Ting Hou, Zhan-Ge Chen, and Yuan Li from Burning Rock Biotech for their valuable assistance in statistical analysis and abstract preparation.
Legal entity responsible for the study
Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences.
Funding
The High-level Hospital Construction Project (Grant No. DFJH201809 to JJ Yang).
Disclosure
Z-X. Chen: Financial Interests, Institutional, Full or part-time Employment: Accurate International Biotechnology. All other authors have declared no conflicts of interest.