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 Koukourakis; Erasmia Xanthopoulou; Ioannis M Koukourakis; Sotirios P Fortis; Nikolaos Kesesidis; Christos Kakouratos; Ioannis Karakasiliotis; Constantin N Baxevanis

doi:10.3390/curroncol30100643

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

Curr Oncol. 2023 Sep 29;30(10):8902-8915. doi: 10.3390/curroncol30100643.

Authors

Michael I Koukourakis¹, Erasmia Xanthopoulou¹, Ioannis M Koukourakis², Sotirios P Fortis³, Nikolaos Kesesidis⁴, Christos Kakouratos¹, Ioannis Karakasiliotis⁴, Constantin N Baxevanis³

Affiliations

¹ Department of Radiotherapy-Oncology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
² Radiation Oncology Unit, 1st Department of Radiology, Aretaieion University Hospital, 11528 Athens, Greece.
³ Cancer Immunology and Immunotherapy Center, Cancer Research Center, Saint Savas Cancer Hospital, 11522 Athens, Greece.
⁴ Laboratory of Biology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece.

Abstract

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.

Keywords: NGS; TP53; ctDNA; gene mutations; head neck cancer; radiotherapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chemoradiotherapy
Circulating Tumor DNA* / genetics
Head and Neck Neoplasms* / drug therapy
Head and Neck Neoplasms* / genetics
High-Throughput Nucleotide Sequencing
Humans
Mutation
Neoplasm Recurrence, Local / genetics

Substances

Circulating Tumor DNA

Grants and funding

This research has been co-financed by the European Regional Development Fund of the European Union and Greek National Funds through the Operational Program Competitiveness, Entrepreneurship, and Innovation, under the call RESEARCH–CREATE–INNOVATE (project code: T2EDK-03266, project acronym, and title: “BIOKAKETRA—Identification of genomic and transcriptomic prognostic bio-signatures in head and neck cancer”).