Head and Neck Unit, The Royal Marsden NHS Foundation Trust, London, United Kingdom; The Institute of Cancer Research, National Institute of Health Research Biomedical Research Centre, London, United Kingdom.
Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Lung and Head & Neck Tumors Unit, Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain.
Cancer Treat Rev. 2024 Jun;127:102746. doi: 10.1016/j.ctrv.2024.102746. Epub 2024 Apr 27.
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.
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.
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.
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.
头颈部鳞状细胞癌（HNSCC）由于其局部复发模式和频繁的表面扩展，为肿瘤内治疗（IT）提供了理想的场景。IT 疗法旨在通过直接将抗肿瘤药物注入病变部位来实现肿瘤消退。然而，关于 HNSCC 的 IT 疗法，缺乏最新的证据。
通过 WebOfScience、ClinicalTrials.gov 以及 ESMO 和 ASCO 会议摘要进行系统文献检索（CRD42023462291），从数据库创建到 2023 年 9 月 12 日，确定用于 HNSCC 患者的 IT 临床试验。报告了疗效和安全性（≥3 级与治疗相关的不良事件[trAEs]）。
经过对系统搜索中确定的 1180 篇文章的评估，纳入了 31 项研究，共治疗了 948 名患者。IT 注射剂分为有或没有电穿孔的化疗药物（k=4，N=268）、溶瘤病毒、质粒和基于细菌的制剂（k=16，N=446）、免疫疗法和 EGFR 靶向疗法（k=5，N=160）、放射增敏粒子（k=2，N=68）和钙电穿孔（k=1，n=6）。EGFR 反义质粒、NBTXR3 放射增敏剂和免疫先天激动剂的总体反应率分别为 83%、81%和 44%。11 项（35%）研究在 IT 注射的基础上添加了系统治疗或放疗。没有研究使用预测生物标志物来指导患者选择。97%的研究为 I 期-II 期。安全性方面，电穿孔和肾上腺素基注射剂试验有显著的局部症状，如坏死、瘘管形成和注射后吞咽困难。几项试验中描述了不同等级的治疗相关肿瘤出血。归因于其他疗法的≥3 级 trAEs 主要包括疲劳等一般症状。在整个系统评价中，有 3 例与注射相关的死亡。
这是首次总结 HNSCC 中所有可用的 IT 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应用。需要继续研究潜在的分子、患者选择、注射安全管理和对照随机试验，以评估其附加效益。
