声波刺猬抑制剂在基底细胞癌中的功效和安全性：一种更新的系统评价和荟萃分析（2009-2022）

皮肤的基底细胞癌（BCC）是美国皮肤癌最常见的形式。在威胁生命的高级BCC中，声波刺猬抑制剂（SSHIS）仍然是局部先进的BCC和转移BCC的杰出治疗选择，我们旨在更好地表征SSHIS的功效和其他临床临床试验的最终搜索，并在此更新的系统审查和荟萃分析中进行更好的表征，并将其纳入Pivotal clinical Frial.an的最终搜索。前瞻性病例系列，以及有关人类受试者的回顾性病历审查。总体响应率（ORR）和完整响应率（CRR）是主要结果。为了进行安全评估，分析了以下不良反应的患病率：肌肉痉挛，肌肉症，脱落性，体重减轻，疲劳，恶心，肌痛，毛发，呕吐，皮肤鳞状细胞癌，增加肌酸激酶，腹泻，减少食欲和孕妇。使用R统计软件进行分析。使用具有固定效应荟萃分析的线性模型以及95％置信区间（CIS）和P值汇总数据。使用Fisher的精确测试计算了分子间差异。荟萃分析中总共包括22项研究（n = 2384名患者）：19项评估功效和安全性的研究，2项仅评估安全性的研究，1项研究仅评估功效。总体而言，所有患者的合并ORR为64.9％（95％CI 48.2-81.6％），这意味着大多数接受SSHIS的患者中至少有部分反应（z = 7.60，p <0.0001）。 Sonidegib的Vismodegib的ORR为68.5％和50.1％。 Vismodegib和Sonidegib最常见的不良反应是肌肉痉挛（分别为70.5％和61.0％），Dysgeusia（分别为58.4％和48.6％）和脱发（分别为59.9％和51.1％）。患者可能会从Vismodegib体验体重减轻（35.1％，p <0.0001）。另外，与接受vismodegib的患者相比，服用Sonidegib的患者经历了更多的恶心，腹泻，肌酸酶水平升高，食欲下降，而接受Vismodegib的患者是对晚期BCC疾病的有效治疗方法。鉴于较高的停药率，因此有必要管理患者期望的管理和实现长期疗效。保持最新发现有关SSHIS的功效和安全性的最新发现至关重要。

Basal cell carcinoma (BCC) of the skin is the most common form of skin cancer in the United States. In life-threatening, advanced BCC, sonic hedgehog inhibitors (SSHis) remain a pre-eminent treatment option for locally advanced BCC and metastatic BCC.In this updated systematic review and meta-analysis, we aimed to better characterize the efficacy and safety of SSHis by including final updates from pivotal clinical trials and additional new recent studies.An electronic database search was performed for articles including clinical trials, prospective case series, and retrospective medical record reviews on human subjects. Overall response rates (ORRs) and complete response rates (CRRs) were the primary outcomes. For safety assessment, the prevalence of the following adverse effects was analyzed: muscle spasms, dysgeusia, alopecia, weight loss, fatigue, nausea, myalgias, vomiting, skin squamous cell carcinoma, increased creatine kinase, diarrhea, decreased appetite, and amenorrhea. Analyses were performed using R statistical software. Data were pooled using linear models with fixed effects meta-analysis for primary analyses, along with 95% confidence intervals (CIs) and p-values. Intermolecular differences were calculated using Fisher's exact test.A total of 22 studies (N = 2384 patients) were included in the meta-analysis: 19 studies assessing both efficacy and safety, 2 studies assessing safety only, and 1 study assessing efficacy only. Overall, the pooled ORR for all patients was 64.9% (95% CI 48.2-81.6%), implicating there is at least a partial response (z = 7.60, p < 0.0001) in most patients receiving SSHis. The ORR for vismodegib was 68.5% and 50.1% for sonidegib. The most common adverse effects for vismodegib and sonidegib were muscle spasms (70.5% and 61.0%, respectively), dysgeusia (58.4% and 48.6%, respectively), and alopecia (59.9% and 51.1%, respectively). Patients were likely to experience weight loss (35.1%, p < 0.0001) from vismodegib. Alternatively, patients taking sonidegib experienced more nausea, diarrhea, increased creatine kinase levels, and decreased appetite compared with those receiving vismodegib.SSHis are an effective treatment for advanced BCC disease. Given the high discontinuation rates, management of patient expectations is warranted for compliance and achieving long-term efficacy. It is essential to stay updated with the latest discoveries on the efficacy and safety of SSHis.