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Detection of circulating tumour DNA after neoadjuvant chemoradiotherapy in patients with locally advanced oesophageal cancer
Author(s) -
Eyck Ben M,
Jansen Maurice PHM,
Noordman Bo Jan,
Atmodimedjo Peggy N,
Wilk Berend J,
Martens John WM,
Helmijr Jean A,
Beaufort Corine M,
Mostert Bianca,
Doukas Michail,
Wijnhoven Bas PL,
Lagarde Sjoerd M,
Lanschot J Jan B,
Dinjens Winand NM
Publication year - 2023
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.6016
Subject(s) - medicine , chemoradiotherapy , biopsy , liquid biopsy , digital polymerase chain reaction , oncology , minimal residual disease , polymerase chain reaction , gastroenterology , cancer , pathology , gene , biology , leukemia , biochemistry
Active surveillance instead of standard surgery after neoadjuvant chemoradiotherapy (nCRT) has been proposed for patients with oesophageal cancer. Circulating tumour DNA (ctDNA) may be used to facilitate selection of patients for surgery. We show that detection of ctDNA after nCRT seems highly suggestive of major residual disease. Tumour biopsies and blood samples were taken before, and 6 and 12 weeks after, nCRT. Biopsies were analysed with regular targeted next‐generation sequencing (NGS). Circulating cell‐free DNA (cfDNA) was analysed using targeted NGS with unique molecular identifiers and digital polymerase chain reaction. cfDNA mutations matching pre‐treatment biopsy mutations confirmed the presence of ctDNA. In total, 31 patients were included, of whom 24 had a biopsy mutation that was potentially detectable in cfDNA (77%). Pre‐treatment ctDNA was detected in nine of 24 patients (38%), four of whom had incurable disease progression before surgery. Pre‐treatment ctDNA detection had a sensitivity of 47% (95% CI 24–71) (8/17), specificity of 85% (95% CI 42–99) (6/7), positive predictive value (PPV) of 89% (95% CI 51–99) (8/9), and negative predictive value (NPV) of 40% (95% CI 17–67) (6/15) for detecting major residual disease (>10% residue in the resection specimen or progression before surgery). After nCRT, ctDNA was detected in three patients, two of whom had disease progression. Post‐nCRT ctDNA detection had a sensitivity of 21% (95% CI 6–51) (3/14), specificity of 100% (95% CI 56–100) (7/7), PPV of 100% (95% CI 31–100) (3/3), and NPV of 39% (95% CI 18–64) (7/18) for detecting major residual disease. The addition of ctDNA to the current set of diagnostics did not lead to more patients being clinically identified with residual disease. These results indicate that pre‐treatment and post‐nCRT ctDNA detection may be useful in identifying patients at high risk of disease progression. The addition of ctDNA analysis to the current set of diagnostic modalities may not improve detection of residual disease after nCRT. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.