32P - Patient derived circulating tumor cell clusters for personalized chemotherapy

Background

The enumeration of circulating tumor cells (CTCs) serves as a surrogate marker for prognosis and assessing the response to chemotherapy. CTCs can manifest as single cells or clusters and the presence of clusters is associated with metastatic disease. Therefore, isolation and characterization of CTC clusters is an important strategy for monitoring disease progression. We explored the utility of drug susceptibility testing on CTC clusters for predicting clinical outcomes.

Methods

We devised a short-term culture protocol to culture CTC clusters isolated from the nucleated blood cells of cancer patients. From a cohort of 100 individuals diagnosed with solid malignancies, 10 ml blood specimens were subjected to RBC lysis and cultured under hypoxic conditions utilizing pre-casted microwell plates. The resulting clusters were categorized according to their compactness as very tight, tight, or loose. Furthermore, the expression profiles of cytokeratins and CD45 within these clusters were examined. Subsequently, the cells derived from these clusters were subjected to drug susceptibility testing against various FDA-approved chemotherapeutic agents. The in vitro drug response data were then correlated with clinical outcomes.

Results

Our study unveiled the presence of CTC clusters demonstrating diverse compactness levels across distinct cancer types. These clusters displayed varying cytokeratin expression profiles, underscoring inherent heterogeneity within them. Remarkably, the compactness of CTC clusters showed a significant correlation with survival outcomes. Additionally, our findings underscore the effectiveness of utilizing in vitro drug susceptibility testing on CTC clusters as an insightful approach for assessing patient responses to chemotherapeutic agents.

Conclusions

Our comprehensive evaluation elucidated the pivotal role of CTC cluster analysis as a promising tool for precisely determining treatment efficacy and predicting favorable patient outcomes.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.