Abstract

Both immune checkpoint inhibitors (ICIs) monotherapy and ICIs-chemo combination therapy have emerged as a treatment option for selected patients with advanced non-small-cell lung cancer (NSCLC). However, few serological biomarkers are available to monitor the treatment efficacy and predict the long-term prognosis. By quantitative determination of folate receptor-positive circulating tumor cell (FR+CTC), this study performed a dymanic monitoring study in NSCLC patients who underwent ICIs based therapy and investigated the correlation of CTC values to predict the prognosis. This study enrolled 38 advanced NSCLC patients with at least one measurable lesion and expected to receive ICIs treatment. Peripheral blood samples were collected before the treatment and after each cycle of ICIs treatment. FR+CTCs were enumerated by negative enrichment using immunomagnetic beads and ligand-targeted polymerase chain reaction methods. The correlation of FR+CTC baseline level and its dynamic changes with radiographic assessment and prognosis was evaluated. Of the 38 patients, 20 received first-line treatment, 9 received second-line treatment, and 9 received third-line treatment or above. CTCs were detected (≥8.7FU/3ml) in 78.9% of patients at baseline. There was no significant difference in baseline CTC values among first-line, second-line and third-line therapy patients. The CTC level decreased 18.65% after one or more cycles in the PR group, while increased 25.43% in the non-response (SD+PD) group. In the prognosis predicting study of first-line ICIs treatment subgroup, the patients treated harboring high baseline CTC level showed shorter median progression free survival time than those with low expression levels (cutoff CTC level=13; PFS: 6.83 vs. 16.30 months, P=0.0116). In sum, these data confirm the predictive significance of baseline CTCs in advanced NSCLC patients with first-line immune checkpoint inhibitors treatment. Further studies are needed to confirm whether the CTC value and its dynamic change correlated with radiological response.

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