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Next-Generation Sequencing Analysis of Mutations in Circulating Tumor DNA from the Plasma of Patients with Head-Neck Cancer Undergoing Chemo-Radiotherapy Using a Pan-Cancer Cell-Free Assay.

Michael I KoukourakisErasmia XanthopoulouIoannis M KoukourakisSotirios P FortisNikolaos KesesidisChristos KakouratosIoannis KarakasiliotisConstantin N Baxevanis
Published in: Current oncology (Toronto, Ont.) (2023)
Using next-generation sequencing (NGS), we investigated DNA mutations in the plasma tumor cell-free circulating DNA (ctDNA) of 38 patients with inoperable squamous cell head neck cancer (SCHNC) before and after the completion of chemoradiotherapy (CRT). Baseline mutations of the TP53 were recorded in 10/38 (26.3%) and persisted in 4/10 patients after CRT. ΤP53 mutations were further detected post CRT in 7/38 additional patients with undetectable mutations at baseline (overall rate 44.7%). Furthermore, 4/38 patients exhibited baseline mutations of the EGFR , AR , FGFR3 , and FBXW3, and four new gene mutations were detected after CRT ( MTOR , EGFR3 , ALK , and SF3B1) . Τ4 stage was related with a significantly higher rate of mutations ( TP53 and overall). Mutations were observed in 8/30 (26.6%) responders (complete/partial response) vs. in 6/8 (75%) of the rest of the patients ( p = 0.03). Significant poorer LRFS was noted for patients with mutations detected before and after CRT ( p = 0.02). Patients who had detectable mutations either before or after CRT had significantly worse DMFS ( p = 0.04 overall, and p = 0.02 for TP53 mutations). It was concluded that assessment of mutations before and after the end of CRT is essential to characterize patients with a high risk of locoregional recurrence or metastatic progression.
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