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Updated: Jan 8, 2026
Patient-Derived Tumor Explants As a "Live" Preclinical Platform for Predicting Drug Resistance in Patients
Published on: February 7, 2021
Predictive Value of Patient-Derived Tumor Cell Cluster-Based Drug Sensitivity Assay in Advanced NSCLC
Yangchun Gu1,2, Leilei Yang3, Hua Zhang4
1Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital, Beijing, China.
Background:
Patient-derived tumor cell cluster (PTC)-based drug sensitivity assays show promise for enabling precision drug selection; however, their predictive value in advanced non-small cell lung cancer (NSCLC) requires further elucidation.
Methods:
To assess the concordance between PTC-based drug sensitivity and clinical outcomes, we conducted a single-center prospective cohort study at Peking University Third Hospital from August 2021 to August 2024. We enrolled 38 consecutive patients, from whom 44 fresh tumor specimens were obtained for PTC-based drug sensitivity assays and compared with paired clinical outcomes of chemotherapy and targeted therapy regimens. Concordance was assessed using the Kappa statistic and receiver operating characteristic curve analysis. A Cox proportional-hazard model was used to identify prognostic factors for progression-free survival (PFS).
Results:
We observed an 81.8% (36/44) concordance between the PTC killing rate (>0% vs 0%) and the best overall clinical response (disease controlled vs disease progression per RECIST v1.1) (Kappa = 0.484, area under the curve (AUC) = 0.740). The concordance with the local response of the biopsied lesions was even higher, at 87.5% (35/40) (Kappa = 0.593, AUC = 0.841). A PTC killing rate >0% was correlated with significantly longer PFS (8.6 vs 2.0 months, P < .001) and emerged as an independent predictor of PFS in multivariate analysis (hazard ratio (HR) 3.507, 95% confidence interval (CI) 1.289-9.536). Exploratory subgroup analysis revealed concordance rates of 73.7% (14/19) for malignant effusion-derived PTCs and 88.0% (22/25) for tumor tissue-derived PTCs; 95.2% (20/21) for first-line therapy and 69.6% (16/23) for later-line therapies; and 80.0% (12/15) for targeted therapy and 85.2% (23/27) for chemotherapy. Notably, the concordance rate reached 100% (14/14) in patients receiving chemotherapy plus immune checkpoint inhibitors.
Conclusions:
These findings validate the predictive value of the PTC-based drug sensitivity assay in guiding personalized treatment for patients with advanced NSCLC and support its clinical translation.
Registration:
Chinese Clinical Trial Registry, Registration No.: ChiCTR2100048791, https://www.chictr.org.cn/showproj.html?proj=129885.
