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

IF 2.7 3区医学 Q3 ONCOLOGY

Clinical and Translational Radiation Oncology Pub Date : 2025-01-08 DOI:10.1016/j.ctro.2025.100915

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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Abstract

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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评估口腔微生物组的放射敏感性以预测头颈癌患者放射性诱导的粘膜炎：一项前瞻性试验。

背景：在开始放射治疗（RT）之前预测口腔黏膜炎（OM）的发生和/或严重程度仍然非常困难。这项前瞻性试验的目的是研究头颈部（H&N）癌症患者口腔角化细胞的离体辐射敏感性是否与严重OM相关。方法：对63例接受（化疗）放疗的h&n癌患者进行健康牙龈粘膜活检，其中58例可用。这些显微活检的角质形成细胞进行体外增殖、照射和随后的细胞扩散试验。将带有细胞悬液的试管置于137Cs Gammacell 40 Exactor （Best Theratronics, Canada）的辐照室中，并以0.63 Gy min-1的剂量率暴露于0、2、4、6或8 Gy。然后立即将细胞悬浮液移液到定制的聚二甲基硅氧烷（PDMS）环中。还分析了人口统计学和临床参数对细胞扩散试验的影响。系统的临床记录OM由专门训练的检查员每周进行两次。结果：大部分患者有淋巴结阳性病变和口咽、口腔肿瘤。绝大多数患者接受了辅助放疗和同期化疗。总体而言，34名（58.6%）参与者在中位剂量为32 Gy后发展为3级OM。没有患者发生≥4级事件。细胞扩散试验面积与3级OM有相关性（p < 0.05）。结论：有必要建立治疗前H&N癌严重OM的可靠预测指标，以便早期处理治疗相关的后遗症。这项前瞻性试验表明，口腔角化细胞内在的离体放射敏感性可能与H&N癌患者rt诱导的OM相关。这种新颖的预测指标需要在更大的前瞻性队列中进行验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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