Supplementary Material for: Efficacy and Safety of Mistletoe Preparations (Viscum album) for Patients with Cancer Diseases

Background: Mistletoe is often used as a complementary approach in oncology. Despite experimental anti-tumour effects and several reviews there remains controversy about its clinical role. Patients and Methods: Potentially relevant trials were identified to perform a systematic review (databases: e.g. EMBASE, MEDLINE; hand search: e.g. bibliographies; search terms: e.g. mistletoe). To be included, randomised or comparative clinical trials at least had to examine mistletoe preparations standardized according to manufacturing process and to describe interventions explicitly. Additionally, cohort studies were included for reasons of external validity. Results were summarised in tables. Results: 18 clinical trials (>6,800 participants) were included. Their internal quality was mostly low. Due to heterogeneity between trials a meta-analysis was impossible. Regarding efficacy, findings were inconsistent regarding life expectancy, relation to tumour entity, dosing and treatment duration. Yet, studies indicate that quality of life (QoL) is improved. As these findings do not seem to be limited to one of the different parenteral mistletoe preparations reviewed the treatment may be summarised under the umbrella term ‘mistletoe therapy’. Regarding safety, 1 serious adverse event (AE) related to mistletoe was described; non-serious AEs were local reactions at injection site. Allergic reactions were rare. Conclusion: Supportive ‘mistletoe therapy’ seems safe and beneficial for QoL in adult patients with solid tumours. But there is an urgent need to confirm its efficacy in patient-centred care in a complex oncological setting. This has to be evaluated systematically in prospective observational trials with validated, multidimensional patient-rated QoL questionnaires and comparisons of different preparations and dosages.

背景：槲寄生（mistletoe）常被用作肿瘤学领域的补充治疗手段。尽管已有实验性抗肿瘤效应相关研究与多篇综述发表，但学界对其临床应用价值仍存在诸多争议。
患者与方法：本研究通过系统综述筛选潜在相关临床试验：检索数据库涵盖EMBASE、MEDLINE等，同时开展手工检索（包括参考文献列表），检索词包含“mistletoe”等。纳入标准如下：随机对照或对照临床试验需至少针对按生产工艺标准化的槲寄生制剂开展研究，并明确描述干预措施；此外，为保证研究的外部效度，本研究同时纳入队列研究。所有研究结果以表格形式汇总呈现。
结果：最终纳入18项临床试验，受试者总人数超过6800名，其中多数研究的内部质量偏低。由于各试验间存在显著异质性，无法开展元分析（meta-analysis）。在疗效方面，现有研究在患者生存期、肿瘤类型、给药剂量与治疗时长等维度的结论并不一致。但多项研究表明，槲寄生治疗可改善患者的生活质量（quality of life, QoL）。鉴于上述获益并非局限于本次综述所涵盖的某一种肠外槲寄生制剂，该类治疗可被统一归类为“槲寄生疗法”。在安全性方面，仅报道1例与槲寄生相关的严重不良事件（adverse event, AE）；非严重不良事件主要为注射部位局部反应，过敏反应较为罕见。
结论：对于实体瘤成年患者，辅助性“槲寄生疗法”安全性良好，且可有效改善患者生活质量。但目前仍亟需在复杂的肿瘤临床场景中，以患者为中心开展照护，并通过前瞻性观察试验系统验证其疗效——此类试验需采用经过验证的多维度患者自评生活质量问卷，并对比不同制剂与给药剂量的差异。