Abstract
Circulating tumor DNA (ctDNA) has emerged as a candidate biomarker for cancer screening. However, studies on the usefulness of ctDNA for postoperative recurrence monitoring are limited. The present study monitored ctDNA in postoperative blood by employing cancer-specific rearrangements. Personalized cancer-specific rearrangements in 25 gastric cancers were analyzed by whole-genome sequencing (WGS) and were employed for ctDNA monitoring with blood up to 12 months after surgery. Personalized cancer-specific rearrangements were identified in 19 samples. The median lead time, which is the median duration between a positive ctDNA detection and recurrence, was 4.05 months. The presence of postoperative ctDNA prior to clinical recurrence was significantly correlated with cancer recurrence within 12 months of surgery (P = 0.029); in contrast, no correlation was found between cancer recurrence and the presence of preoperative ctDNA, suggesting the clinical usefulness of postoperative ctDNA monitoring for cancer recurrence in gastric cancer patients. However, the clinical application of ctDNA can be limited by the presence of ctDNA non-shedders (42.1%, 8/19) and by inconsistent postoperative ctDNA positivity.
Highlights
The standard methodologies for monitoring cancer recurrence in patients with gastric cancer after surgical resection are radiographic imaging and peritoneal cytologic examination[1,2], but these methods lack the sensitivity required for detecting micrometastatic tumors
By analyzing the Circulating tumor DNA (ctDNA) levels in postoperative blood with personalized cancer-specific rearrangements instead of mutations, we confirmed the presence of ctDNA at a median lead time of 4.05 months and found that postoperative ctDNA positivity prior to clinical recurrence was significantly correlated with cancer recurrence within 12 months of radical surgery (P = 0.029)
Our study confirmed the clinical usefulness of ctDNA monitoring for cancer recurrence in gastric cancer patients after curative surgical resection
Summary
The standard methodologies for monitoring cancer recurrence in patients with gastric cancer after surgical resection are radiographic imaging and peritoneal cytologic examination[1,2], but these methods lack the sensitivity required for detecting micrometastatic tumors. The main aims of the present retrospective study were as follows: (1) to conduct a feasibility test for the detection of low-level postoperative ctDNA in serially collected blood samples in the early phases of clinical recurrence in gastric cancer patients who had undergone surgical resection of the primary tumor, and (2) to evaluate the usefulness of postoperative ctDNA for monitoring cancer recurrence. For these purposes, we retrospectively and preferentially enrolled patients with recurrence and available serial plasma samples obtained up to 12 months after curative surgical resection as well as available frozen primary tumor samples. Personalized cancer-specific rearrangements after analyzing the rearranged sequences from whole-genome sequencing (WGS) in gastric cancers were employed to monitor ctDNA in serially collected plasma samples
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