Correlation of drug susceptibility testing on short term cultures of CTCs positively with clinical outcomes in non-small cell lung cancer.

Abstract

e21177 Background: Enumeration of circulating tumor cells (CTCs) is rapidly emerging as a minimally invasive and reliable technique for monitoring disease progression and patient’s response to treatment. However, its utility beyond enumeration in clinical management of cancer remains scarcely explored. Being biologically similar to both primary and secondary tumors, CTCs may help in identification of most efficacious therapies. In this study, we propose a method for short term culture of CTCs thereby allowing to evaluate the drug susceptibility testing in individual patients. Methods: We obtained peripheral blood samples from 20 advanced stage lung cancer patients undergoing treatment at Kidwai Memorial Institute of Oncology, Bangalore, India. These blood samples were processed and cultured on ellipsoidal microwells maintained at hypoxic conditions (1% O2). The CTC clusters were seeded onto 96 well plates coated with Matrigel and treated with the same drug regimen as the respective patients. The viability of the cells was measured using CellTitre-Glo. Results: Of the 20 samples, tight cluster formation was observed in four samples and drug susceptibility testing was performed. Based on clinical treatment received, we treated CTCs with combination of pemetrexed and carboplatin at respective Cmax concentrations of 5.68 and 3.68 µg/ml. The combination drug treatment resulted in decreased viability of CTCs to 30.7%. Notably, the CT scan images demonstrated significant reduction of pleural effusion in patient following treatment with carboplatin and pemetrexed, thus correlating with our in vitro drug susceptibility finding. Conclusions: In this proof of concept study, we demonstrate the feasibility of utilizing in vitro drug susceptibility testing on CTCs as an approach to guide patient specific chemotherapeutic treatment approaches, thus opening avenues for personalized treatments.