Personalized drug screening of patient-derived tumor-like cell clusters based on specimens obtained from percutaneous transthoracic needle biopsy in patients with lung malignancy: a real-world study

Abstract

Background

Patient-derived xenografts and organoids were the most common patient-derived tumor models in vitro that were utilized in personalized drug screening, and the establishment rate and duration required to be improved. Patient-derived tumor-like cell clusters (PTCs) could be established within ten days for drug screening, with high establishment rate and accuracy in predicting clinical outcomes. This study aims to explore the accuracy of PTCs based on specimens obtained from percutaneous transthoracic needle biopsy (PTNB) in lung malignancy (LM) patients, and to investigate the predictors for the success of PTC culture.

Materials and methods

This retrospective cohort study included LM patients who underwent image-guided PTNB, and the specimens were used for PTC culture, which was followed by personalized drug screening of chemotherapy and molecular targeted therapy, and the accuracy was validated by previous or further treatments. The predictors of the success of PTC culture were identified by univariable and multivariable analyses.

Results

A total of 68 LM patients were enrolled, consisting of 57, 7, and 4 patients with non-small cell lung cancer, small cell lung cancer, and lung metastases, respectively. Pneumothorax was the predominant adverse event for PTNB, with an incidence rate of 20.6% (14/68). PTC models based on PTNB specimens were established successfully for 56 patients in 3.8 ± 2.3 days, with an 82.4% success rate. Five patients had not received treatments before or after PTC culture. PTC drug screening reveals 88.2% (45/51) overall consistency in predicting clinical outcomes. Necrotic area over half of the tumor (hazard ratio, 0.121; 95% confidence interval, 0.025–0.598; P = 0.010) was identified as the negative predictor for the success of PTC culture.

Conclusions

PTC culture based on PTNB specimens could be established in 82.4% of LM patients, with a high accuracy in predicting clinical outcomes. Excessive necrosis in the tumor may predict the failure of PTC culture. Image-guided PTNB targeting enhanced or fluorodeoxyglucose‌ avid regions on images might contribute to improving the success rate of PTC culture.