Cancer Communications (Dec 2023)

Residual circulating tumor DNA after adjuvant chemotherapy effectively predicts recurrence of stage II‐III gastric cancer

  • Shu‐Qiang Yuan,
  • Run‐Cong Nie,
  • You‐Sheng Huang,
  • Ying‐Bo Chen,
  • Si‐Yu Wang,
  • Xiao‐Wei Sun,
  • Yuan‐Fang Li,
  • Ze‐Kun Liu,
  • Yan‐Xing Chen,
  • Yi‐Chen Yao,
  • Yu Xu,
  • Hai‐Bo Qiu,
  • Yao Liang,
  • Wei Wang,
  • Ze‐Xian Liu,
  • Qi Zhao,
  • Rui‐Hua Xu,
  • Zhi‐Wei Zhou,
  • Feng Wang

DOI
https://doi.org/10.1002/cac2.12494
Journal volume & issue
Vol. 43, no. 12
pp. 1312 – 1325

Abstract

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Abstract Background Circulating tumor DNA (ctDNA) is a promising biomarker for predicting relapse in multiple solid cancers. However, the predictive value of ctDNA for disease recurrence remains indefinite in locoregional gastric cancer (GC). Here, we aimed to evaluate the predictive value of ctDNA in this context. Methods From 2016 to 2019, 100 patients with stage II/III resectable GC were recruited in this prospective cohort study (NCT02887612). Primary tumors were collected during surgical resection, and plasma samples were collected perioperatively and within 3 months after adjuvant chemotherapy (ACT). Somatic variants were captured via a targeted sequencing panel of 425 cancer‐related genes. The plasma was defined as ctDNA‐positive only if one or more variants detected in the plasma were presented in at least 2% of the primary tumors. Results Compared with ctDNA‐negative patients, patients with positive postoperative ctDNA had moderately higher risk of recurrence [hazard ratio (HR) = 2.74, 95% confidence interval (CI) = 1.37–5.48; P = 0.003], while patients with positive post‐ACT ctDNA showed remarkably higher risk (HR = 14.99, 95% CI = 3.08‐72.96; P < 0.001). Multivariate analyses indicated that both postoperative and post‐ACT ctDNA positivity were independent predictors of recurrence‐free survival (RFS). Moreover, post‐ACT ctDNA achieved better predictive performance (sensitivity, 77.8%; specificity, 90.6%) than both postoperative ctDNA and serial cancer antigen. A comprehensive model incorporating ctDNA for recurrence risk prediction showed a higher C‐index (0.78; 95% CI = 0.71–0.84) than the model without ctDNA (0.71; 95% CI = 0.64–0.79; P = 0.009). Conclusions Residual ctDNA after ACT effectively predicts high recurrence risk in stage II/III GC, and the combination of tissue‐based and circulating tumor features could achieve better risk prediction.

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