Departments of Dermatology and Pediatrics, Northwestern University Feinberg School of Medicine, 676 North St Clair Street, Suite 1600, Chicago, IL, 60611, USA.
Galter Health Sciences Library & Learning Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Orphanet J Rare Dis. 2024 May 21;19(1):206. doi: 10.1186/s13023-024-03190-1.
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.
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 Cases with administration of systematic therapies and unpublished outcomes regarding death were tracked with corresponding authors.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.
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.
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）患者死亡的主要原因，RDEB 是一种罕见的遗传性皮肤病。RDEB-cSCC 治疗结果主要在病例报告中描述。系统研究很少。本系统综述旨在评估 RDEB-cSCC 的病理生理学、临床特征和结果，重点关注最近免疫疗法和抗 EGFR 治疗的结果和机制。
2024 年 2 月，我们对表皮松解症和 cSCC 进行了系统的文献检索，使用了 PubMed、Embase、Cochrane 对照试验中心注册库、ClinicalTrials.gov 和 EudraCT 数据库。通过与相应的作者联系，跟踪了接受系统治疗和未公布死亡结果的病例。两名独立的评审员进行了数据提取和偏倚风险评估。在最初的搜索中，有 1132 篇参考文献，确定了 163 篇相关文章，其中包括 59 篇病例报告、7 项队列研究、49 篇摘要、47 篇体外/体内实验和 1 篇生物信息学研究。从这些研究中，纳入了 157 例 RDEB-cSCC。大多数 RDEB-cSCC 分化良好（64.1%）、溃疡（59.6%），且至少 2cm 大小（77.6%），中位诊断年龄为 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 治疗和免疫治疗也分别于 2009 年和 2019 年开始报告。在 50 例可获得首次 cSCC 诊断至死亡时间的病例中。根据其治疗方案分层，中位生存时间为 1.85 年（手术+化疗，n=6）、2 年（手术，n=19）、4.0 年（+抗 EGFR 治疗，n=10）、4 年（手术+放疗，n=9）、4.6 年（+免疫治疗，n=4）和 9.5 年（手术+化疗+放疗，n=2）。与治疗相关的不良事件主要限于免疫治疗的伤口愈合不良和抗 EGFR 治疗的恶心和疲劳。
尽管在罕见疾病中样本量有限带来了挑战，但本系统综述提供了 RDEB 中 cSCC 治疗选择的概述。当手术治疗选择已用尽时，添加免疫治疗和/或抗 EGFR 治疗可能会延长患者的生存时间。然而，很难将延长的生存时间归因于任何单一治疗，因为 RDEB-cSCC 通常使用多种治疗方法进行治疗。
