Liquid Biopsy Serial Monitoring of Treatment Responses and Relapse in Advanced Esophageal Squamous Cell Carcinoma

Abstract

(1) Background: Early predictive markers to track treatment responses are needed for advanced esophageal squamous cell carcinoma (ESCC) patients. We examined the prognostication and risk stratification role of liquid biopsy serial monitoring for this deadly cancer. (2) Methods: Circulating tumor cells (CTCs) and plasma cell-free DNA (cfDNA) were isolated from 60 ESCC patients treated by chemotherapy (CT) at five serial timepoints: baseline (CTC1/cfDNA1), CT pre-cycle III (CTC2/cfDNA2), CT post-cycle IV, end of CT and relapse. (3) Results: In 45/57 ESCC patients with evaluable CTC counts at CT pre-cycle III, positive CTC2 (≥3 CTCs) is independently associated with response at interim reassessment and progression-free survival (PFS) in multivariate analysis. In 42/57 ESCC patients with changes of CTC1/CTC2 and cfDNA1/cfDNA2, patients categorized into four risk groups based on the number of favorable and unfavorable changes of CTC1/CTC2 and cfDNA1/cfDNA2, were independently associated with overall survival (OS) by multivariate analysis. (4) Conclusions: CTC counts at pre-cycle III are independently associated with response at interim reassessment and PFS. Combined changes of CTC counts and cfDNA levels from baseline to pre-cycle III are independently associated with OS. Longitudinal liquid biopsy serial monitoring provides complementary information for prediction and prognosis for CT responses in advanced ESCC.

The Diagnostic and Prognostic Value of a Liquid Biopsy for Esophageal Cancer: A Systematic Review and Meta-Analysis

“…The simplest technique of ccfDNA quantification is concentration reading with a fluorometer. Ko demonstrated that increasing ccfDNA concentration levels during two cycles of chemotherapy can predict early disease progression and poor outcomes [ 75 ]. On the other hand, the quantification of total ccfDNA presents a risk for the contamination of non-specific ccfDNA from normal tissue, which causes poor sensitivity and specificity for the diagnosis or prediction of cancer-related outcomes.…”

“…Eleven studies were enrolled for OS analysis, with a total of 854 EC patients [ 13 , 25 , 26 , 27 , 29 , 32 , 54 , 75 , 82 , 83 , 84 , 85 ]. In this cohort, the average age was 63.6 years (61.5–66) and the median CTC positivity rate was 46.4% (18.0–79.7).…”

“…A total of ten studies were enrolled for the PFS analysis of 1712 EC patients [ 8 , 39 , 40 , 42 , 47 , 49 , 51 , 52 , 54 , 55 , 75 , 89 , 90 , 92 , 93 , 94 ]. In this cohort, the average age was 62.3 years (58.9–66), and the median CTC positive rate was 35.5% (16.8–54.2).…”

“…Next, the derived sensitivity and 1-specificity values from each report (a total of thirty-two molecules from 22 studies [ 49 , 50 , 54 , 56 , 57 , 58 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 72 , 75 , 78 , 79 , 80 , 95 , 96 , 97 ]) were plotted ( Figure 4 c). The logarithmic regression curve, with 95% CIs, was constructed to evaluate the heterogeneity of each diagnostic value, and three molecules (lncSNHG1 [ 63 ], miR-216a [ 67 ], and a combination of miRNAs (miR16-5p, miR197-5p, and miR92a-3p) [ 58 ]) were considered as favorable candidates for the early detection of ECs.…”

Hallmark microRNA signature in liquid biopsy identifies hepatocellular carcinoma and differentiates it from liver metastasis

“…Our group has previously conducted technical validation and established clinical utilities of circulating tumor cells in colorectal, lung, breast, gastric, liver, prostate, esophageal, and nasopharyngeal cancers [27][28][29]. The clinical application of combining miRNA, circulating tumor cell [27][28][29], and bioinformatics technology [30,31] merits further exploration. To sum up, we discovered circulating microRNA signatures for identifying HCC and demonstrated the promising performance of the liquid biopsy assay for HCC identification and differential diagnosis.…”