Supplementary Material for: Impact of Clustering Oral Symptoms in the Pathogenesis of Radiation Caries: A Systematic Review

Radiation-related caries (RRC) is a disease with a high potential for destruction of the dentition, which impairs quality of life in head-and-neck (HN) cancer (HNC) patients who undergo radiotherapy. In light of the recently described “clustering of oral symptoms theory,” the present systematic review (PROSPERO CRD42019132709) aims to assess HN and gastrointestinal (GI) symptom clusters among HNC patients and discusses how these indirect effects of cancer therapy play a pivotal role in the pathophysiology of RRC. The search was performed at PubMed, Scopus, and Embase and resulted in 11 studies that met the inclusion criteria. Data extraction was performed with respect to the presence of HN/GI symptom clusters among HNC patients. The methodological data of the studies included were assessed using the MAStARI and GRADE instruments. The most prevalent reported HN symptoms were dysphagia, xerostomia, and pain. Taste alterations and fatigue were also commonly reported by the patients. Loss of appetite and weight loss were regularly reported in the studies, as well as nausea and vomiting. The results of the present study suggest that HNC treatment generates clusters of oral symptoms, leading to dietary changes, impaired oral hygiene, enamel fragility, and a highly cariogenic oral environment, which may impact the risk for RRC. A better understanding of oral symptom clustering could be of considerable clinical significance for the oral health and quality of life of HNC patients. Therefore, contemporary protocols of RRC prevention must take this broader treatment scenario of symptom clusters such as oral side effects into account.

放射性龋（Radiation-related caries, RRC）是一种具有极高牙列破坏风险的疾病，会损害接受放射治疗的头颈部（head-and-neck, HN）癌症（HNC）患者的生活质量。鉴于近期提出的“口腔症状集群理论（clustering of oral symptoms theory）”，本项系统综述（PROSPERO CRD42019132709）旨在评估HNC患者的头颈部与胃肠道（gastrointestinal, GI）症状集群，并探讨癌症治疗的这些间接效应如何在RRC的病理生理过程中发挥关键作用。本研究在PubMed、Scopus及Embase数据库中开展检索，最终纳入符合纳入标准的11项研究。研究人员针对HNC患者头颈部/胃肠道症状集群的存在情况开展了数据提取工作。采用MAStARI与GRADE工具（MAStARI and GRADE instruments）对纳入研究的方法学数据进行了质量评估。报告频率最高的头颈部症状为吞咽困难、口干症与疼痛。患者亦常报告味觉改变与疲劳。研究中还频繁提及食欲减退、体重减轻，以及恶心呕吐症状。本研究结果显示，HNC治疗可引发口腔症状集群，进而导致饮食结构改变、口腔卫生受损、牙釉质脆弱以及致龋性极强的口腔环境，这可能会升高RRC的发病风险。深入理解口腔症状集群现象，对于HNC患者的口腔健康与生活质量具有重要的临床意义。因此，当前的RRC预防方案必须将口腔副作用等更为广泛的症状集群治疗场景纳入考量。