Prediction of Pathologic Complete Response in Esophageal Squamous Cell Carcinoma Using Preoperative Serum Small Ribonucleic Acid Obtained After Neoadjuvant Chemoradiotherapy

Ann Surg Oncol. 2025 Jan;32(1):570-580. doi: 10.1245/s10434-024-16247-z. Epub 2024 Oct 17.

Abstract

Background: The authors hypothesized that small ribonucleic acid (sRNA) obtained from blood samples after neoadjuvant therapy from patients treated with neoadjuvant chemoradiation therapy (NACRT) could serve as a novel biomarker for predicting pathologic complete response (pCR).

Methods: This study included 99 patients treated with esophagectomy after NACRT between March 2010 and October 2021 whose blood samples were collected between the end of NACRT and surgery. Next-generation sequencing (NGS) was used to analyze sRNAs from the blood samples. A predictive model for pCR comprising micro-RNA isoforms (isomiR), transfer RNA (tRNA)-derived sRNAs (tsRNAs), and clinical factors was constructed using cross-validation.

Results: Of the 99 patients, pCR was diagnosed for 30 and non-pCR for 69 of the patients. Among sRNAs, the isomiRs of let-7b and miR-93 and the tsRNA group derived from tRNA-Gly-CCC/GCC were identified as predictive factors. The clinical factors included a decrease in the maximum standardized uptake value (SUVmax) at the primary site, clinical complete response post-NACRT, preoperative biopsy, and post-NACRT carcinoembryonic antigen levels. The combined predictive model for pCR (C-PM) was established using the three sRNAs and four clinical factors. The area under the curve for the C-PM was 0.84, which was a significant factor in the multivariate analysis (odds ratio, 89.41; 95 % confidence interval 8.1-987.5; p < 0.001).

Conclusions: Pathologic complete response after NACRT can be predicted by a predictive model constructed from preoperative clinical factors obtained via minimally invasive procedures and sRNA identified by NGS. Preoperative pCR prediction may influence treatment decision-making after NACRT.

Keywords: Esophagus; Neoadjuvant chemoradiation therapy; Pathological complete response; Serum small RNA; Squamous cell carcinoma.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor* / blood
  • Chemoradiotherapy
  • Chemoradiotherapy, Adjuvant
  • Esophageal Neoplasms* / blood
  • Esophageal Neoplasms* / pathology
  • Esophageal Neoplasms* / therapy
  • Esophageal Squamous Cell Carcinoma / blood
  • Esophageal Squamous Cell Carcinoma / pathology
  • Esophageal Squamous Cell Carcinoma / therapy
  • Esophagectomy*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • MicroRNAs / blood
  • Middle Aged
  • Neoadjuvant Therapy*
  • Pathologic Complete Response
  • Prognosis
  • Retrospective Studies
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • MicroRNAs