Evaluating the radiosensitivity of the oral microbiome to predict radiation-induced mucositis in head and neck cancer patients: A prospective trial

Background: Predicting the occurrence and/or severity of oral mucositis (OM) before commencing radiotherapy (RT) remains very difficult. The aim of this prospective trial was to investigate whether the ex-vivo radiation sensitivity of oral keratinocytes from head and neck (H&N) cancer patients c...

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Main Authors: Andreas R. Thomsen, Elsa Beatriz Monroy Ordonez, Michael Henke, Benedikt Luka, Jörg Sahlmann, Henning Schäfer, Vivek Verma, Nadine Schlueter, Anca-Ligia Grosu, Tanja Sprave
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Language:English
Published: Elsevier 2025-03-01
Series:Clinical and Translational Radiation Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405630825000059
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author Andreas R. Thomsen
Elsa Beatriz Monroy Ordonez
Michael Henke
Benedikt Luka
Jörg Sahlmann
Henning Schäfer
Vivek Verma
Nadine Schlueter
Anca-Ligia Grosu
Tanja Sprave
author_facet Andreas R. Thomsen
Elsa Beatriz Monroy Ordonez
Michael Henke
Benedikt Luka
Jörg Sahlmann
Henning Schäfer
Vivek Verma
Nadine Schlueter
Anca-Ligia Grosu
Tanja Sprave
author_sort Andreas R. Thomsen
collection DOAJ
description Background: Predicting the occurrence and/or severity of oral mucositis (OM) before commencing radiotherapy (RT) remains very difficult. The aim of this prospective trial was to investigate whether the ex-vivo radiation sensitivity of oral keratinocytes from head and neck (H&N) cancer patients correlates with severe OM. Methods: Oral microbiopsies of healthy gingival mucosa were collected from 63H&N cancer patients undergoing (chemo)RT, of which 58 samples were useable. Keratinocytes from these microbiopsies underwent ex-vivo proliferation, irradiation, and subsequently the cell spreading assay. Tubes with the cell suspension were placed within the irradiation chamber of a 137Cs Gammacell 40 Exactor (Best Theratronics, Canada) and exposed to 0, 2, 4, 6, or 8 Gy at a dose rate of 0.63 Gy min−1. Cell suspension was then immediately pipetted into custom-made polydimethylsiloxane (PDMS) rings.The effect of demographic and clinical parameters on the cell spreading assay were also analyzed. Systematic clinical recording of OM was conducted twice a week by a specially trained examiner. Results: Most patients had node-positive disease and cancer of the oropharynx or oral cavity. The vast majority of patients received adjuvant RT and concurrent chemotherapy. Overall, 34 (58.6 %) participants developed grade 3 OM after a median dose of 32 Gy. No patient experienced a grade ≥ 4 event. There was a correlation between the cell spreading assay area and grade 3 OM (p < 0.05), equivalent to approximately 0.5 Gy dose. Demographic and clinical parameters had no significant impact on the cell spreading assay (p > 0.05 for all). Conclusions: It is necessary to establish reliable predictors of severe OM before treatment in H&N cancer to allow early management of treatment-related sequelae. This prospective trial illustrates that the intrinsic ex-vivo radiosensitivity of oral keratinocytes could be correlated with RT-induced OM in patients with H&N cancer. This novel predictor requires validation in larger prospective cohorts.
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spelling doaj-art-894ee49273044d51ba93f4e0184c6cfe2025-01-30T05:14:30ZengElsevierClinical and Translational Radiation Oncology2405-63082025-03-0151100915Evaluating the radiosensitivity of the oral microbiome to predict radiation-induced mucositis in head and neck cancer patients: A prospective trialAndreas R. Thomsen0Elsa Beatriz Monroy Ordonez1Michael Henke2Benedikt Luka3Jörg Sahlmann4Henning Schäfer5Vivek Verma6Nadine Schlueter7Anca-Ligia Grosu8Tanja Sprave9Department of Radiation Oncology, University Hospital of Freiburg, Robert-Koch-Strasse 3, 79106 Freiburg, Germany; German Cancer Consortium (DKTK) Partner Site Freiburg, German Cancer Research Center, Germany; Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Radiation Oncology, University Hospital of Freiburg, Robert-Koch-Strasse 3, 79106 Freiburg, Germany; German Cancer Consortium (DKTK) Partner Site Freiburg, German Cancer Research Center, Germany; Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Radiation Oncology, University Hospital of Freiburg, Robert-Koch-Strasse 3, 79106 Freiburg, Germany; German Cancer Consortium (DKTK) Partner Site Freiburg, German Cancer Research Center, Germany; Faculty of Medicine, University of Freiburg, Freiburg, GermanyHannover Medical School (MHH), Department of Conservative Dentistry, Periodontology and Preventive Dentistry, Hannover, GermanyInstitute for Medical Biometry and Statistics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Radiation Oncology, University Hospital of Freiburg, Robert-Koch-Strasse 3, 79106 Freiburg, Germany; German Cancer Consortium (DKTK) Partner Site Freiburg, German Cancer Research Center, Germany; Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USAHannover Medical School (MHH), Department of Conservative Dentistry, Periodontology and Preventive Dentistry, Hannover, GermanyDepartment of Radiation Oncology, University Hospital of Freiburg, Robert-Koch-Strasse 3, 79106 Freiburg, Germany; German Cancer Consortium (DKTK) Partner Site Freiburg, German Cancer Research Center, Germany; Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Radiation Oncology, University Hospital of Freiburg, Robert-Koch-Strasse 3, 79106 Freiburg, Germany; German Cancer Consortium (DKTK) Partner Site Freiburg, German Cancer Research Center, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany; Corresponding author at: University of Freiburg, Department of Radiation Oncology, Robert-Koch Strasse 3, 79106 Freiburg, Germany.Background: Predicting the occurrence and/or severity of oral mucositis (OM) before commencing radiotherapy (RT) remains very difficult. The aim of this prospective trial was to investigate whether the ex-vivo radiation sensitivity of oral keratinocytes from head and neck (H&N) cancer patients correlates with severe OM. Methods: Oral microbiopsies of healthy gingival mucosa were collected from 63H&N cancer patients undergoing (chemo)RT, of which 58 samples were useable. Keratinocytes from these microbiopsies underwent ex-vivo proliferation, irradiation, and subsequently the cell spreading assay. Tubes with the cell suspension were placed within the irradiation chamber of a 137Cs Gammacell 40 Exactor (Best Theratronics, Canada) and exposed to 0, 2, 4, 6, or 8 Gy at a dose rate of 0.63 Gy min−1. Cell suspension was then immediately pipetted into custom-made polydimethylsiloxane (PDMS) rings.The effect of demographic and clinical parameters on the cell spreading assay were also analyzed. Systematic clinical recording of OM was conducted twice a week by a specially trained examiner. Results: Most patients had node-positive disease and cancer of the oropharynx or oral cavity. The vast majority of patients received adjuvant RT and concurrent chemotherapy. Overall, 34 (58.6 %) participants developed grade 3 OM after a median dose of 32 Gy. No patient experienced a grade ≥ 4 event. There was a correlation between the cell spreading assay area and grade 3 OM (p < 0.05), equivalent to approximately 0.5 Gy dose. Demographic and clinical parameters had no significant impact on the cell spreading assay (p > 0.05 for all). Conclusions: It is necessary to establish reliable predictors of severe OM before treatment in H&N cancer to allow early management of treatment-related sequelae. This prospective trial illustrates that the intrinsic ex-vivo radiosensitivity of oral keratinocytes could be correlated with RT-induced OM in patients with H&N cancer. This novel predictor requires validation in larger prospective cohorts.http://www.sciencedirect.com/science/article/pii/S2405630825000059Head and neck cancerRadiation therapyMucositisPredictionKeratinocytesOral mucosa biopsy
spellingShingle Andreas R. Thomsen
Elsa Beatriz Monroy Ordonez
Michael Henke
Benedikt Luka
Jörg Sahlmann
Henning Schäfer
Vivek Verma
Nadine Schlueter
Anca-Ligia Grosu
Tanja Sprave
Evaluating the radiosensitivity of the oral microbiome to predict radiation-induced mucositis in head and neck cancer patients: A prospective trial
Clinical and Translational Radiation Oncology
Head and neck cancer
Radiation therapy
Mucositis
Prediction
Keratinocytes
Oral mucosa biopsy
title Evaluating the radiosensitivity of the oral microbiome to predict radiation-induced mucositis in head and neck cancer patients: A prospective trial
title_full Evaluating the radiosensitivity of the oral microbiome to predict radiation-induced mucositis in head and neck cancer patients: A prospective trial
title_fullStr Evaluating the radiosensitivity of the oral microbiome to predict radiation-induced mucositis in head and neck cancer patients: A prospective trial
title_full_unstemmed Evaluating the radiosensitivity of the oral microbiome to predict radiation-induced mucositis in head and neck cancer patients: A prospective trial
title_short Evaluating the radiosensitivity of the oral microbiome to predict radiation-induced mucositis in head and neck cancer patients: A prospective trial
title_sort evaluating the radiosensitivity of the oral microbiome to predict radiation induced mucositis in head and neck cancer patients a prospective trial
topic Head and neck cancer
Radiation therapy
Mucositis
Prediction
Keratinocytes
Oral mucosa biopsy
url http://www.sciencedirect.com/science/article/pii/S2405630825000059
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