Franz J Hilke1, Francesc Muyas2, Jakob Admard3, Beate Kootz3, Dominik Nann4, Stefan Welz5, Olaf Rieß6, Daniel Zips5, Stephan Ossowski6, Christopher Schroeder7, Kerstin Clasen8. 1. Institute of Medical Genetics and Applied Genomics, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany; Charité - Universitätsmedizin Berlin, Department of Dermatology, Venereology and Allergology, Germany. 2. Institute of Medical Genetics and Applied Genomics, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany; Universitat Pompeu Fabra (UPF), Barcelona, Spain. 3. Institute of Medical Genetics and Applied Genomics, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany. 4. Institute of Pathology and Neuropathology, Comprehensive Cancer Center and University Hospital Tübingen, Germany. 5. Department of Radiation Oncology, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) partner site Tübingen, Germany. 6. Institute of Medical Genetics and Applied Genomics, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany; DFG NGS Competence Center Tübingen (NCCT), University of Tübingen, Germany. 7. Institute of Medical Genetics and Applied Genomics, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany. Electronic address: Christopher.schroeder@med.uni-tuebingen.de. 8. Department of Radiation Oncology, Medical Faculty and University Hospital, Eberhard Karls University Tübingen, Germany.
Abstract
PURPOSE: Definitive radiochemotherapy (RCTX) with curative intent is one of the standard treatment options in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Despite this intensive therapy protocol, disease recurrence remains an issue. Therefore, we tested the predictive capacity of liquid biopsies as a novel biomarker during RCTX in patients with HNSCC. MATERIAL AND METHODS: We sequenced the tumour samples of 20 patients with locally advanced HNSCC to identify driver mutations. Subsequently, we performed a longitudinal analysis of circulating tumour DNA (ctDNA) dynamics during RCTX. Deep sequencing and UMI-based error suppression for the identification of driver mutations and HPV levels in the plasma enabled treatment-response monitoring prior, during and after RCTX. RESULTS: In 85% of all patients ctDNA was detectable, showing a significant correlation with the gross tumour volume (p-value 0.032). Additionally, the tumour allele fraction in the plasma was negatively correlated with the course of treatment (p-value <0.05). If ctDNA was detectable at the first follow-up, disease recurrence was seen later on. Circulating HPV DNA (cvDNA) could be detected in three patients at high levels, showing a similar dynamic behaviour to the ctDNA throughout treatment, and disappeared after treatment. CONCLUSIONS: Monitoring RCTX treatment-response using liquid biopsy in patients with locally advanced HNSCC is feasible. CtDNA can be seen as a surrogate marker of disease burden, tightly correlating with the gross tumour volume prior to the treatment start. The observed kinetic of ctDNA and cvDNA showed a negative correlation with time and treatment dosage in most patients.
PURPOSE: Definitive radiochemotherapy (RCTX) with curative intent is one of the standard treatment options in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Despite this intensive therapy protocol, disease recurrence remains an issue. Therefore, we tested the predictive capacity of liquid biopsies as a novel biomarker during RCTX in patients with HNSCC. MATERIAL AND METHODS: We sequenced the tumour samples of 20 patients with locally advanced HNSCC to identify driver mutations. Subsequently, we performed a longitudinal analysis of circulating tumour DNA (ctDNA) dynamics during RCTX. Deep sequencing and UMI-based error suppression for the identification of driver mutations and HPV levels in the plasma enabled treatment-response monitoring prior, during and after RCTX. RESULTS: In 85% of all patients ctDNA was detectable, showing a significant correlation with the gross tumour volume (p-value 0.032). Additionally, the tumour allele fraction in the plasma was negatively correlated with the course of treatment (p-value <0.05). If ctDNA was detectable at the first follow-up, disease recurrence was seen later on. Circulating HPV DNA (cvDNA) could be detected in three patients at high levels, showing a similar dynamic behaviour to the ctDNA throughout treatment, and disappeared after treatment. CONCLUSIONS: Monitoring RCTX treatment-response using liquid biopsy in patients with locally advanced HNSCC is feasible. CtDNA can be seen as a surrogate marker of disease burden, tightly correlating with the gross tumour volume prior to the treatment start. The observed kinetic of ctDNA and cvDNA showed a negative correlation with time and treatment dosage in most patients.
Authors: Sarah M Dermody; Catherine T Haring; Chandan Bhambhani; Muneesh Tewari; J Chad Brenner; Paul L Swiecicki Journal: Curr Treat Options Oncol Date: 2021-02-08
Authors: Kyrillus S Shohdy; Dario M Villamar; Yen Cao; Janson Trieu; Kristin S Price; Rebecca Nagy; Scott T Tagawa; Ana M Molina; Cora N Sternberg; David M Nanus; Juan Miguel Mosquera; Olivier Elemento; Guru P Sonpavde; Petros Grivas; Nicholas J Vogelzang; Bishoy Morris Faltas Journal: Br J Cancer Date: 2022-01-19 Impact factor: 7.640
Authors: Vasudha Mishra; Alka Singh; Xiangying Chen; Ari J Rosenberg; Alexander T Pearson; Alex Zhavoronkov; Peter A Savage; Mark W Lingen; Nishant Agrawal; Evgeny Izumchenko Journal: Br J Cancer Date: 2021-12-07 Impact factor: 7.640
Authors: Franciele H Knebel; Louise J Barber; Alice Newey; Dimitrios Kleftogiannis; Andrew Woolston; Beatrice Griffiths; Kerry Fenwick; Fabiana Bettoni; Maurício Fernando Silva Almeida Ribeiro; Leonardo da Fonseca; Frederico Costa; Fernanda Cunha Capareli; Paulo M Hoff; Jorge Sabbaga; Anamaria A Camargo; Marco Gerlinger Journal: Cancers (Basel) Date: 2020-12-11 Impact factor: 6.639