Early dynamics of circulating tumor DNA predict chemotherapy responses for patients with esophageal cancer

Abstract

We investigated whether early circulating tumor DNA (ctDNA) changes, measured using digital PCR (dPCR), can predict later chemotherapy responses in esophageal squamous cell cancer (ESCC). We compared the dynamics of ctDNA and tumor volumes during chemotherapy in 42 ESCC. The accuracy of predictions of later chemotherapy responses were evaluated by the ratio of the variant allele frequency (VAF) of ctDNA (post-/pre-ctDNA) and the total tumor volume (post-/pre-volume) before and after an initial chemotherapy cycle using a receiver-operating characteristic curve analysis. Total positive and negative objective responses (ORs) were defined as either >50% or ≤50% reductions, respectively, in the total tumor volume at the end of first-line chemotherapy. Mutation screening of 43 tumors from 42 patients revealed 96 mutations. The pretreatment dPCR-ctDNA data were informative in 38 patients, using 70 selected mutations (1–3 per patient). The areas under the curve (AUCs) for the post-/pre-volume and post-/pre-ctDNA levels used in predicting the total OR were 0.85 and 0.88, respectively. The optimal cutoff value of post-/pre-ctDNA was 0.13. In 20 patients with post-/pre-volume ≥50%, the total OR could be predicted by the post-/pre-ctDNA with high accuracy; the AUC by post-/pre-ctDNA was higher than that by post-/pre-volume (0.85 vs 0.76, respectively). Patients with low post-/pre-ctDNA (n = 18) had a significantly better overall survival rate than those with high post-/pre-ctDNA (n = 20; P = 0.03). Early ctDNA changes after an initial cycle of chemotherapy predict later responses to treatment with high accuracy in ESCC patients.

Impact of sensitive circulating tumor DNA monitoring on CT scan intervals during postoperative colorectal cancer surveillance

“…31 We previously demonstrated that, in contrast to next-generation sequencing (NGS), frequent ctDNA monitoring by dPCR enabled early relapse prediction, treatment efficacy evaluation, and disease-free corroboration in the management of gastrointestinal cancers, including CRC. [32][33][34][35] Here, we examined results of ctDNA assays from over 1,500 plasma samples and found that ctDNA monitoring by dPCR can provide early relapse detection and disease-free corroboration at molecular level during postoperative CRC surveillance as compared to conventional CTS and CEA monitoring.…”

“…The dPCR assay for quantitative monitoring of ctDNA levels was performed as described previously. [32][33][34][35] Briefly, specific primers and probes labeled for wild-type and mutant alleles were specifically designed for each mutation identified in a primary tumor, using Hypercool Primer & Probe™ technology (Nihon Gene Research Laboratories, Sendai, Japan). For frequently recurring missense mutations, commercially available primer/probe sets were used (Thermo Fisher Scientific, Waltham, MA and Quantdetect, Inc, Tokyo, Japan).…”

“…31 We previously demonstrated that, in contrast to next-generation sequencing (NGS), frequent ctDNA monitoring by dPCR enabled early relapse prediction, treatment efficacy evaluation, and disease-free corroboration in the management of gastrointestinal cancers, including CRC. 32–35…”

Liquid biopsy in lung cancer: significance in diagnostics, prediction, and treatment monitoring

“…CTC analysis can theoretically provide more comprehensive and representative information regarding tumor deposition; however, it also has many clinical limitations. Because the content of CTCs in peripheral blood is very low, further exploration is needed in order to learn how to effectively reduce background cells, efficiently enrich CTCs, and improve the accuracy of CTC detection [ 17 ]. CTCs are generally tumor cells that fall off from the primary focus, metastasis, or surgery and enter the peripheral blood.…”

“…ctDNA, small nucleic acids released by apoptotic or necrotic tumor cells, is a type of cfDNA and encodes the genes of tumor cells [ 23 ]. Most ctDNA fragments are double-stranded fragments with a length of 160–200 base pairs, which is roughly the same as the length of nucleosomes [ 17 ]. The amount of ctDNA entering the blood is affected by many factors, such as tumor location, size, metastasis, vascular infiltration, tumor status, and stage.…”