Clinical and Translational Medicine (Nov 2022)
Prognostic value of circulating tumour DNA during post‐radiotherapy surveillance in locally advanced esophageal squamous cell carcinoma
Abstract
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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