Malignant effusion aspirate for use in constructing organoids model to assist individualized treatment of advanced non-small cell lung cancer.

Abstract

e20526 Background: Organoids derived from cancer patients are considered to represent the overall appearance of the original tumor in lung cancer. With the in-depth study of molecular mechanisms and the development of new drugs, the survival time of advanced non-small cell lung cancer has been greatly extended. However, when it comes to the back-end treatment, they often have limited amounts of fresh tissue samples or cannot complete puncture, which affects the successfully establishment of organoids. Some patients often have malignant pleural effusion (MPE) requiring repeated aspiration, so it is clinically easy to obtain. Our goal was to culture organoids from malignant effusion of advanced NSCLC patients (LCO), and explore and analyze the consistency of drug sensitivity with clinical practice. Methods: In this study, malignant pleural effusion specimens of 39 patients with NSCLC were collected and complete clinical information was obtained.The partially paired successfully modeled organoids and the original malignant effusion were sequenced by WES(N = 7) and RNA(N = 6) for genetic background consistency.All successfully cultured organoids were subjected to drug sensitivity test, and the drug sensitivity results were compared with the actual therapeutic effect of clinical patients. Results: We successfully established 34 LCOs with a success rate of 87.2% . LCOs retained the mutation spectrum of the matching primary tumor. TP53 and EGFR were the most frequently mutated genes, occurring in 83.3% (5 of 6) and 66.7% (4 of 6) of effusion samples. On average, LCOs retained an 93.2% overlap of the most frequently lung cancer gene mutational variants from the parental MPE samples.The gene expression in the paired LCOs and effusion samples were compared, demonstrating an average 80% overlap in gene expression between the LCOs and the matching effusion samples.The clinical outcomes of the 25 patients (27 rounds of treatment) and their LCOs pharmaco-phenotyping results are analyzed. Notably, 94.7% of the treatments, which include at least one drug that was tested to be sensitive or moderately responsive by LCOs, achieved partial response or stable disease. However, 62.5% of the treatments, which do not include any drug that was tested to be sensitive or moderately responsive by LCOs, developed progressive disease. Overall, the LCO pharmaco-phenotyping results are highly correlated with clinical outcomes, with 85.2% accuracy (95% CI, 67.5–94.1%), 85.7% sensitivity (95% CI, 62.6–96.2%), and 83.3% specificity (95% CI, 36.5–99.1%). Conclusions: The effusion and LCOs have high concordance of genomic profiling. Organoid culture from malignant effusions of lung cancer can be used as a platform for drug sensitivity testing. These LCOs may be helpful in individualized treatment of NSCLC.