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

BackgroundThe 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. MethodsTreatment-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 (T-0), week 4 of RT/CRT (T-1), 1-3 (T-2) and 3-6 months post-RT/CRT (T-3). ctDNA was analysed using next-generation sequencing of 474 cancer-relevant genes. ResultsA 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 T-1 (hazard ratio, HR: 3.60, 95% confidence interval, CI: 1.30-10.01) or T-2 (HR: 5.45, 95% CI: 1.72-17.26) indicated inferior progression-free survival (PFS). ctDNA clearance between T-0-T-1 (HR: 0.31, 95% CI: 0.08-1.13) or T-0-T-2 (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 T-1 was a potential indicator of high local recurrence risks (HR: 4.43, 95% CI: 1.31-15.04). ConclusionsctDNA 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.

Automated summary

In this study, ctDNA was identified as a robust biomarker for early detection of disease progression and prognosis stratification after RT/CRT 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.