Clinical and Translational Medicine (Nov 2022)

Prognostic value of circulating tumour DNA during post‐radiotherapy surveillance in locally advanced esophageal squamous cell carcinoma

  • Xin Wang,
  • Nuo Yu,
  • Guowei Cheng,
  • Tao Zhang,
  • Jianyang Wang,
  • Lei Deng,
  • Jiao Li,
  • Xiaotian Zhao,
  • Yang Xu,
  • Peng Yang,
  • Na Bai,
  • Yin Li,
  • Nan Bi

DOI
https://doi.org/10.1002/ctm2.1116
Journal volume & issue
Vol. 12, no. 11
pp. n/a – n/a

Abstract

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Abstract Background The potential of circulating tumour DNA (ctDNA) as a reliable biomarker for relapse/metastasis early detection and prognosis in esophageal squamous cell carcinoma (ESCC) after radiotherapy/chemoradiotherapy (RT/CRT) initiation requires comprehensive investigation. Methods Treatment‐naive locally advanced ESCC patients with available baseline plasma samples were prospectively enrolled from November 2018 to January 2020. RT/CRT was delivered with a simultaneous integrated boost of radiation dose. Serial plasma samples were collected at baseline (T0), week 4 of RT/CRT (T1), 1‐3 (T2) and 3‐6 months post‐RT/CRT (T3). ctDNA was analysed using next‐generation sequencing of 474 cancer‐relevant genes. Results A total of 128 plasma samples from 40 eligible patients were analysed (median age: 64 [range: 40‐78], 88% males, 95% stage III/IV), and the median follow‐up time was 20.6 months (range: 12.2‐33.3). During the post‐RT/CRT surveillance including 36 patients, radiological progression was observed in 16 patients, and 69% (11/16) had detectable post‐RT/CRT ctDNA prior to radiological progression, with a median lead time of 4.4 months compared with radiological imaging. ctDNA positivity at T1 (hazard ratio, HR: 3.60, 95% confidence interval, CI: 1.30‐10.01) or T2 (HR: 5.45, 95% CI: 1.72‐17.26) indicated inferior progression‐free survival (PFS). ctDNA clearance between T0‐T1 (HR: 0.31, 95% CI: 0.08‐1.13) or T0‐T2 (HR: 0.11; 95% CI: 0.02‐0.61) was associated with relatively favourable PFS. Similar results were obtained when focusing on patients without esophagectomy after RT/CRT. Notably, detectable ctDNA at T1 was a potential indicator of high local recurrence risks (HR: 4.43, 95% CI: 1.31‐15.04). Conclusions ctDNA was identified as a robust biomarker for early detection of disease progression and post‐RT/CRT prognosis stratification in ESCC. Detectable ctDNA at week 4 of RT/CRT might indicate higher local recurrence risks, implying the potential clinical utility of ctDNA tests in guiding post‐RT/CRT treatments for locoregional control in ESCC.

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