Tumor Burden Monitoring with Circulating Tumor DNA During Treatment in Patients with Esophageal Squamous Cell Carcinoma

Yosuke Morimoto, Satoru Matsuda, Hirofumi Kawakubo, Kohei Nakamura, Ryota Kobayashi, Kazuhiko Hisaoka, Jun Okui, Masashi Takeuchi, Eriko Aimono, Kazumasa Fukuda, Rieko Nakamura, Hideyuki Saya, Hiroshi Nishihara, Yuko Kitagawa

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Background: To guide appropriate treatment strategy, an accurate tumor monitoring modality that reflects tumor burden during neoadjuvant treatment is required for esophageal squamous cell carcinoma (ESCC). We aimed to investigate the clinical utility of circulating tumor DNA (ctDNA) in plasma in patients who received neoadjuvant chemotherapy (NAC) followed by esophagectomy. Patients and Methods: Longitudinally collected plasma samples for ctDNA combined with genomic DNA from primary lesions were obtained from patients with histologically confirmed ESCC who underwent NAC followed by subtotal esophagectomy. Next-generation sequencing was performed to identify mutations from the plasma and the primary tumor. The relationships between changes in ctDNA and the pathological response and recurrence were assessed in patients with locally advanced ESCC. Results: In pretreatment samples from 13 patients, multiple concordant mutations in ctDNA and primary tumors were observed in 11 patients (85%), who were classified as ctDNA positive before treatment. The ctDNA positive rate after NAC correlated with the pathological response (responders, 25%; nonresponders, 100%; p = 0.007). The risk of recurrence increased significantly in patients with positive ctDNA after surgery in analysis of 16 patients; the 1-year recurrence-free survival rates were 90 and 0% in ctDNA-negative and ctDNA-positive groups, respectively (p = 0.0008). In two patients with postoperative recurrence, ctDNA was detected approximately 5.5 months earlier than the diagnosis using radiographical imaging. Conclusions: ctDNA is a promising biomarker for predicting pathological response and postoperative recurrence in ESCC. To demonstrate the external validity, we are currently preparing a multicenter prospective study.

Original languageEnglish
Pages (from-to)3747-3756
Number of pages10
JournalAnnals of Surgical Oncology
Volume30
Issue number6
DOIs
Publication statusPublished - 06-2023

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

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