背景:头颈部鳞状细胞癌(HNSCC)是瘤内治疗(IT)的理想方案,由于其局部复发模式和频繁的表面延伸。IT疗法旨在通过直接将抗肿瘤剂注射到病变中来影响肿瘤消退。然而,缺乏有关HNSCC中IT疗法的最新证据。
方法:使用WebOfScience进行了系统的文献检索(CRD42023462291),ClinicalTrials.gov,以及ESMO和ASCO的会议摘要,确定HNSCC患者的IT临床试验,从数据库创建到9月12日,2023年。报告疗效和安全性(治疗相关不良事件≥3级[trAEs])。
结果:在评估了通过系统搜索确定的1180篇文章之后,包括31项治疗948名患者的研究。IT注射剂分为有或没有电穿孔的化疗(k=4,N=268),溶瘤病毒,质粒,以细菌为基础(k=16,N=446),免疫疗法和基于EGFR的疗法(k=5,N=160),放射增强剂颗粒(k=2,N=68),和钙电穿孔(k=1,n=6)。EGFR反义质粒,NBTXR3放射增强剂和免疫先天激动剂显示出最佳的总体反应率,83%,分别为81%和44%。11项(35%)研究在IT注射中增加了全身性治疗或放射疗法。没有研究使用预测性生物标志物来指导患者选择。97%的研究为I-II期。安全方面,电穿孔和肾上腺素为基础的注射试验有明显的局部症状,如坏死,瘘管形成和注射后吞咽困难。在几项试验中描述了各种级别的治疗相关肿瘤出血。可归因于其他疗法的≥3级trAE主要包括一般症状,例如疲劳。在整个系统评价中,有3例注射相关死亡。
结论:这是第一个总结HNSCC中IT的所有可用证据的综述。截至今天,IT疗法缺乏足够的证据来推荐其在临床实践中的使用。继续研究潜在分子,患者选择,需要安全的注射给药和随机对照试验来评估其额外获益.
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) presents an ideal scenario for intratumoral therapies (IT), due to its local recurrence pattern and frequent superficial extension. IT therapies aim to effect tumor regression by directly injecting antineoplastic agents into lesions. However, there is a lack of updated evidence regarding IT therapies in HNSCC.
METHODS: A systematic literature search (CRD42023462291) was conducted using WebOfScience, ClinicalTrials.gov, and conference abstracts from ESMO and ASCO, identifying for IT clinical trials in patients with HNSCC, from database creation to September 12th, 2023. Efficacy as well as safety (grade ≥ 3 treatment-related adverse events[trAEs]) were reported.
RESULTS: After evaluation of 1180 articles identified by the systematic search, 31 studies treating 948 patients were included. IT injectables were categorized as chemotherapies with or without electroporation (k = 4, N = 268), oncolytic viruses, plasmids, and bacteria-based (k = 16, N = 446), immunotherapies and EGFR-based therapies (k = 5, N = 160), radioenhancer particles (k = 2, N = 68), and calcium electroporation (k = 1, n = 6). EGFR-antisense plasmids, NBTXR3 radioenhancer and immune innate agonists show best overall response rates, at 83 %, 81 % and 44 % respectively. Eleven (35 %) studies added systemic therapy or radiotherapy to the IT injections. No study used predictive biomarkers to guide patient selection. 97 % studies were phase I-II. Safety-wise, electroporation and epinephrine-based injectable trials had significant local symptoms such as necrosis, fistula formation and post-injection dysphagia. Treatment-related tumor haemorrhages of various grades were described in several trials. Grade ≥ 3 trAEs attributable to the other therapies mainly comprised general symptoms such as fatigue. There were 3 injectable-related deaths across the systematic review.
CONCLUSIONS: This is the first review to summarize all available evidence of IT in HNSCC. As of today, IT therapies lack sufficient evidence to recommend their use in clinical practice. Continuing research on potential molecules, patient selection, safe administration of injections and controlled randomized trials are needed to assess their added benefit.