Survival, Chemotherapy and Chemosensitivity Predicted by CTC Cultured In Vitro of SCLC Patients

Abstract

PurposeThe prognosis for small cell lung cancer (SCLC) patients receiving later-line treatment is very poor and there is still no standard treatments after the second-line setting. Analyzing the susceptibility of chemotherapeutic drugs with circulating tumor cells (CTCs) cultured in vitro may contribute to optimize the therapeutic regimen. However, so far CTCs have been barely used for studying their chemosensitivity due to the lack of technology to obtain wholly intact and viable CTCs.MethodsBased on a retrospective study of the therapeutic response of 99 patients with unresectable SCLC, the CTC count in 14 SCLC patients was detected before and after chemotherapy to evaluate its role as a potential marker of response. Furthermore, the drug susceptibility of CTCs cultured in vitro obtained from ClearCell FX® System was tested and the therapy response was evaluated.ResultsAll of the 99 patients received the first-line chemotherapy and the objective response rate (ORR) was 74.7%. A total of 36 patients received the second-line therapy and the average duration was 2.6 months, and only 11 cases out of them received the third-line therapy but no one responded. The change of CTC counts was identified to be correlated with therapy response. However all the five SCLC patients who were administered with the drugs according to the drug susceptibility test of CTCs for two cycles underwent progression of disease.ConclusionThe results showed that the responses of chemotherapy are very poor in later lines and the drug susceptibility test using CTCs primary cultured in vitro may not benefit the improvement of therapeutic regimen of SCLC patients.

Assessment of Different Circulating Tumor Cell Platforms for Uveal Melanoma: Potential Impact for Future Routine Clinical Practice

“…Patient-derived xenografts (PDX) from previously isolated CTCs have been reported with the Vortex (VTX-1) [ 72 ], ISET [ 61 ] and Cellsearch [ 67 ] platforms. The chemosensitivity of previously isolated CTCs has been reported in vitro with the ClearCell FX device [ 73 ]. Inertial focusing technologies (e.g., with the Vortex (VTX-1) and ClearCell FX) are known to exert little mechanical stress on CTCs and are thought to yield a higher rate of viable CTCs compared to other technologies [ 24 ].…”

“…Using a single UM cell line allowed a direct comparison to be made and the experimental conditions to be standardized, thus limiting variability due to the cells and experimental conditions. Only one study has compared ctDNA levels with the CTC count using the Cellsearch platform [ 73 ]. In other solid malignancies, only a few studies have directly compared various CTC isolation techniques [ 29 ].…”

Circulating tumour cells in patients with lung cancer universally indicate poor prognosis

“…Although indicators for poor prognosis, CTCs may serve as a source of tumour DNA/RNA for next-generation sequencing-based therapeutic prediction [65] and even enable blood-derived tumour cell lines for ex vivo testing of targeted treatments predicted in silico [7].…”

“…The persistence of CTCs after completion of treatment (even more so after curative treatment such as surgical resection) strongly predicts early recurrence and poor survival [ 63 , 64 ]. Although indicators for poor prognosis, CTCs may serve as a source of tumour DNA/RNA for next-generation sequencing-based therapeutic prediction [ 65 ] and even enable blood-derived tumour cell lines for ex vivo testing of targeted treatments predicted in silico [ 7 ].…”

A novel nomogram predicting cancer-specific survival in small cell lung cancer patients with brain metastasis

“…Lung cancer is one of the most common malignancies as well as the leading cause of cancer-related death among both men and women in the United States (US), which can be categorized into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) ( 1 ). SCLC accounts for approximately 15% of all the lung cancer ( 2 ). Each year, SCLC comprises an estimated 250,000 new cases and more than 200,000 deaths all over the world ( 3 ).…”