Koch Alexander, Reinhardt Philipp, Elicin Olgun, Aebersold Daniel M, Schanne Daniel H
Department of Radiation Oncology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.
Department of Radiation Oncology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland; Graduate School for Health Sciences, University of Bern, Switzerland.
Radiother Oncol. 2025 Feb;203:110689. doi: 10.1016/j.radonc.2024.110689. Epub 2024 Dec 18.
Radiotherapy is essential for treating head and neck cancer but often leads to severe toxicity. Traditional predictors include anatomical location, tumor extent, and dosimetric data. Recently, biomarkers have been explored to better predict and understand toxicity. This review aims to summarize the current literature, assess data quality, and guide future research.
Two reviewers independently screened EMBASE and PubMed for studies published between 2010 and 2023. Endpoints were dermatitis, mucositis, sticky saliva/xerostomia, and dysphagia. Statistical analysis was performed using R, and bias assessed via a modified QUIPS questionnaire. Pathway analysis was conducted using gProfiler. The study adhered to PRISMA and COSMOS-E guidelines and was registered in the PROSPERO database (#CRD42023361245).
Of 2,550 abstracts, 69 publications met the inclusion criteria. These studies involved a median of 81 patients, primarily male (75 %), with common primary tumors in the nasopharynx (32 %) and oropharynx (27 %). Most patients (84 %) had advanced disease (stage III/IV). The most frequently studied biomarkers were DNA-based single-nucleotide polymorphisms (SNPs, 59 %), salivary proteins (13 %), and bacteria (10 %). Ten statistically-significant biomarkers (all SNPs) in low-bias publications were identified, particularly in DNA repair and cell detoxification pathways. Data quality was often poor and few validation studies were present in the dataset.
This review provides an overview of the research landscape, highlights research gaps and provides recommendations for future research directions. We identified several potential biomarkers, particularly in DNA repair pathways, that align with current understanding of radiation-induced cell damage. However, the overall data quality was poor, with key clinical variables often missing. Overall, rigorous standardization of reporting, validation studies and multi-center collaborations to increase study power and sample sizes are necessary to build high-level evidence for clinical application.
放射治疗是治疗头颈癌的重要手段，但常导致严重毒性。传统的预测指标包括解剖位置、肿瘤范围和剂量学数据。近年来，人们一直在探索生物标志物，以更好地预测和理解毒性。本综述旨在总结当前文献，评估数据质量，并指导未来研究。
两名 reviewers 独立检索 EMBASE 和 PubMed 中 2010 年至 2023 年发表的研究。观察终点为皮炎、粘膜炎、唾液粘稠/口干和吞咽困难。使用 R 进行统计分析，并通过改良的 QUIPS 问卷评估偏倚。使用 gProfiler 进行通路分析。本研究遵循 PRISMA 和 COSMOS-E 指南，并在 PROSPERO 数据库（#CRD42023361245）中注册。
在 2550 篇摘要中，69 篇出版物符合纳入标准。这些研究中位纳入 81 例患者，主要为男性（75%），常见原发肿瘤位于鼻咽（32%）和口咽（27%）。大多数患者（84%）患有晚期疾病（III/IV 期）。研究最频繁的生物标志物是基于 DNA 的单核苷酸多态性（SNPs，59%）、唾液蛋白（13%）和细菌（10%）。在低偏倚出版物中鉴定出 10 个具有统计学意义的生物标志物（均为 SNPs），特别是在 DNA 修复和细胞解毒通路中。数据质量通常较差，数据集中几乎没有验证研究。
本综述概述了研究概况，突出了研究差距，并为未来研究方向提供了建议。我们确定了几种潜在的生物标志物，特别是在 DNA 修复通路中，这些生物标志物与目前对辐射诱导细胞损伤的理解一致。然而，总体数据质量较差，关键临床变量常常缺失。总体而言，需要严格规范报告、进行验证研究以及开展多中心合作以提高研究效能和样本量，从而为临床应用建立高级别证据。
