背景:侵袭性皮肤鳞状细胞癌(cSCC)是隐性营养不良性大疱性表皮松解症(RDEB)的主要死亡原因,一种罕见的起泡性皮肤病。病例报告中主要描述了RDEB-cSCC治疗的结果。缺乏系统的研究。本系统综述旨在评估病理生理学,临床特征,以及RDEB-CSCC的结果,重点关注近期免疫疗法和抗EGFR治疗的结果和机制。
结果:2024年2月,使用PubMed对大疱性表皮松解症和cSCC进行了系统的文献检索,Embase,Cochrane中央控制试验登记册,ClinicalTrials.gov,和EudraCT数据库。与相应的作者一起追踪了给予系统治疗和未发表的死亡结果的病例。数据提取和偏倚风险评估由两名独立审阅者进行。在原始搜索中的1132个参考文献中,确定了163篇相关文章,代表59例病例报告,7项队列研究,49摘要,47个体外/体内实验,和1个生物信息学研究。从这些,纳入157例RDEB-cSCC。大多数RDEB-cSCC分化良好(64.1%),溃疡(59.6%),尺寸至少为2厘米(77.6%),诊断时的中位年龄为30岁(范围6-68.4)。手术是主要的治疗形式(n=128),其次是化疗和放疗。抗EGFR治疗和免疫疗法也分别于2009年和2019年开始报道。从首次cSCC诊断到死亡的生存时间在50例中是可用的。当按他们的治疗方案分层时,中位生存时间为1.85年(手术+化疗,n=6),2年(仅手术,n=19),4.0年(+抗EFGR治疗,n=10),4年(手术+放疗,n=9),4.6年(+免疫疗法,n=4),9.5年(手术+化疗+放疗;n=2)。治疗相关的不良事件主要限于免疫疗法的伤口愈合受损和抗EGFR疗法的恶心和疲劳。
结论:尽管罕见疾病的样本量有限,本系统综述概述了RDEB中cSCC的治疗方案.当手术治疗方案用尽时,免疫疗法和/或抗EGFR疗法的加入可以延长患者的生存期.然而,很难将延长生存期归因于任何单一治疗,因为多种治疗方式通常用于治疗RDEB-cSCC。
BACKGROUND: Invasive cutaneous squamous cell carcinomas (cSCC) are a leading cause of death in recessive dystrophic epidermolysis bullosa (RDEB), a rare blistering genodermatosis. Outcomes of RDEB-cSCC therapies have primarily been described in case reports. Systematic studies are scarce. This systematic review aims to assess the pathophysiology, clinical characteristics, and outcomes of RDEB-cSCCs, with a focus on results and mechanisms of recent immunotherapies and anti-EGFR treatments.
RESULTS: A systematic literature search of epidermolysis bullosa and cSCC was performed in February 2024, using PubMed, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and EudraCT databases. Cases with administration of systematic therapies and unpublished outcomes regarding death were tracked with corresponding authors. Data extraction and risk of bias assessment was performed by two independent reviewers. Of 1132 references in the original search, 163 relevant articles were identified, representing 59 case reports, 7 cohort studies, 49 abstracts, 47 in-vitro/in-vivo experiments, and 1 bioinformatic study. From these, 157 cases of RDEB-cSCCs were included. The majority of RDEB-cSCCs were well-differentiated (64.1%), ulcerated (59.6%), and at least 2 cm in size (77.6%), with a median age at diagnosis of 30 years old (range 6-68.4). Surgery was the primary form of treatment (n = 128), followed by chemotherapy and radiotherapy. Anti-EGFR therapy and immunotherapy was also reported beginning in 2009 and 2019, respectively. Survival time from first cSCC diagnosis to death was available in 50 cases. When stratified by their treatment regimen, median survival time was 1.85 years (surgery + chemotherapy, n = 6), 2 years (surgery only, n = 19), 4.0 years (+ anti-EFGR therapy, n = 10), 4 years (surgery + radiotherapy, n = 9), 4.6 years (+ immunotherapy, n = 4), and 9.5 years (surgery + chemotherapy + radiotherapy; n = 2). Treatment-related adverse events were primarily limited to impaired wound healing for immunotherapies and nausea and fatigue for anti-EGFR therapies.
CONCLUSIONS: Despite the challenges of a limited sample size in a rare disease, this systematic review provides an overview of treatment options for cSCCs in RDEB. When surgical treatment options have been exhausted, the addition of immunotherapy and/or anti-EGFR therapies may extend patient survival. However, it is difficult to attribute extended survival to any single treatment, as multiple therapeutic modalities are often used to treat RDEB-cSCCs.