肿瘤治疗电场在头颈部癌症中的应用前景

doi:10.19438/j.cjoms.2023.05.001

中国口腔颌面外科杂志 ›› 2023, Vol. 21 ›› Issue (5): 425-431.doi: 10.19438/j.cjoms.2023.05.001

肿瘤治疗电场在头颈部癌症中的应用前景

李晨曦^1,2,3, 龚忠诚^1,2,*, 赵化荣^4,*, 丁明超⁵, 刘慧⁶

1.新疆医科大学第一附属医院（附属口腔医院）口腔颌面肿瘤外科,新疆乌鲁木齐 830054;
2.新疆维吾尔自治区口腔医学研究所,新疆乌鲁木齐 830054;
3.华中科技大学同济医学院附属协和医院口腔医学中心,口腔颌面发育与再生湖北省重点实验室,湖北武汉 430022;
4.新疆医科大学第一附属医院肿瘤中心一病区（头颈）,新疆乌鲁木齐 830054;
5.中国人民解放军空军军医大学第三附属医院创伤与正颌外科,军事口腔医学国家重点实验室,口腔疾病国家临床医学研究中心,陕西省口腔疾病临床医学研究中心,陕西西安 710032;
6.上海市口腔医院口腔颌面外科,上海市颅颌面发育与疾病重点实验室,上海 200031

收稿日期:2023-01-29 修回日期:2023-02-23 出版日期:2023-09-20 发布日期:2023-10-11
通讯作者: 龚忠诚,E-mail: gump0904@aliyun.com;赵化荣,E-mail：xydyfyzhr@163.com。^*共同通信作者
作者简介:李晨曦（1989-）,男,博士,主治医师,E-mail: lichenximed@163.com
基金资助:
国家自然科学基金（82360481）; 口腔颌面发育与再生湖北省重点实验室开放课题基金（2022kqhm008）; 陕西省牙颌疾病临床医学研究中心开放课题（西安交通大学口腔医学院）（2020YHJB01）; 新疆维吾尔自治区天山创新团队课题项目（2021D14001）; 自治区科研创新项目（XJ2023G174）; 自治区自然科学基金重点项目

Application prospect of tumor treating fields technology in head and neck cancer

LI Chen-xi^1,2,3, GONG Zhong-cheng^1,2, ZHAO Hua-rong⁴, DING Ming-chao⁵, LIU Hui⁶

1. Oncological Department of Oral and Maxillofacial Surgery, First Affiliated Hospital of Xinjiang Medical University, School & Hospital of Stomatology Xinjiang Medical University. Urumqi 830054, Xinjiang Uygur Autonomous Region;
2. Stomatological Research Institute of Xinjiang Uygur Autonomous Region. Urumqi 830054, Xinjiang Uygur Autonomous Region;
3. Center of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration. Wuhan 430022, Hubei Province;
4. First Ward of Oncological Department, Cancer Center, First Affiliated Hospital of Xinjiang Medical University. Urumqi 830054, Xinjiang Uygur Autonomous Region;
5. State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Traumatology & Orthognathic Surgery, Third Affiliated Hospital of Air Force Medical University. Xi'an 710032, Shaanxi Province;
6. Department of Oral and Maxillofacial Surgery, Shanghai Stomatological Hospital & School of Stomatology, Fudan University; Shanghai Key Laboratory of Craniomaxillofacial Development and Disease, Fudan University. Shanghai 200031, China

Received:2023-01-29 Revised:2023-02-23 Online:2023-09-20 Published:2023-10-11

摘要/Abstract

摘要： 近年来,随着免疫制剂和分子靶向药物的研发进展,针对恶性肿瘤的治疗取得了一定突破,但其仍然是目前全球疾病死亡的主要原因。肿瘤治疗电场（tumor treating fields, TTFields）是一种全新的非侵入性癌症治疗方法。TTFields可提供给肿瘤局部一个低强度（1~3 V/cm）、中频（100~300 kHz）的交变电场,通过破坏肿瘤细胞有丝分裂期的染色体分离及诱发介电泳现象,使细胞结构紊乱,发生凋亡。TTFields对正常细胞和癌细胞的敏感参数不同,对静止期细胞则没有作用,故其抗肿瘤治疗的毒副作用小、创伤小,具有很大潜力。TTFields的有效性和安全性已在多形性胶质母细胞瘤的Ⅲ期临床试验中得到验证,在其他实体瘤也相继开展了临床研究。本文就TTFields的最新研究进展进行综述,并阐述其微观机制及讨论在头颈癌中的应用前景。

关键词: 医学物理学, 头颈部, 恶性肿瘤, 肿瘤电场治疗

Abstract: In recent years, major breakthroughs have been made in the treatment of malignant tumours with research and development progress of immunologic agents and molecular targeted drugs, but it is still the main cause of global disease death. Tumour treating fields (TTFields) is a new non-invasive approach to cancer treatment. TTFields can provide a kind of low-intensity (1-3 V/cm), intermediate frequency (100-300 kHz) alternating electric fields delivered locally to the tumour, which can destroy the chromosome segregation of mitotic tumour cells and induce dielectrophoresis to arise cell structure disturbance and apoptosis. The sensitive parameters of TTFields for normal and cancerous cells are different, but TTFields has no effect on quiescent cells. Hence, it has the advantages of fewer side effects and less trauma, and has great potential. Additionally, its efficacy and safety have been verified in phase III clinical trials of glioblastoma multiforme. Some clinical trials on TTFields have also been carried out in other kinds of solid tumours. This article reviewed the latest research progress of TTFields, expounding its micromechanism and discussing its application prospects in head and neck cancer.

Key words: Medical physics, Head and neck, Malignancy, Tumor treating fields

中图分类号:

R739.8

李晨曦, 龚忠诚, 赵化荣, 丁明超, 刘慧. 肿瘤治疗电场在头颈部癌症中的应用前景[J]. 中国口腔颌面外科杂志, 2023, 21(5): 425-431.

LI Chen-xi, GONG Zhong-cheng, ZHAO Hua-rong, DING Ming-chao, LIU Hui. Application prospect of tumor treating fields technology in head and neck cancer[J]. China J Oral Maxillofac Surg, 2023, 21(5): 425-431.

参考文献

[1] Siegel RL, Miller KD, Fuchs HE, et al.Cancer statistics, 2022[J]. CA Cancer J Clin, 2022, 72(1): 7-33.
[2] Auger S, Davis A, Rosenberg AJ.Recommendations for care of survivors of head and neck cancer[J]. JAMA, 2022, 328(16): 1637-1638.
[3] Cohen EEW, Bell RB, Bifulco CB, et al.The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC)[J]. J Immunother Cancer, 2019, 7(1):184-214.
[4] Green SE, McCusker MG, Mehra R. Emerging immune checkpoint inhibitors for the treatment of head and neck cancers[J]. Expert Opin Emerg Drugs, 2020, 25(4): 501-514.
[5] Massarelli E, Lin H, Ginsberg LE, et al.Phase Ⅱ trial of everolimus and erlotinib in patients with platinum-resistant recurrent and/or metastatic head and neck squamous cell carcinoma[J]. Ann Oncol, 2015, 26(7): 1476-1480.
[6] Kirson ED, Gurvich Z, Schneiderman R, et al.Disruption of cancer cell replication by alternating electric fields[J]. Cancer Res, 2004, 64(9): 3288-3295.
[7] Kirson ED, Dbaly V, Tovarys F, et al.Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors[J]. Proc Natl Acad Sci USA, 2007, 104(24): 10152-10157.
[8] Stupp R, Taillibert S, Kanner A, et al.Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial[J]. JAMA, 2017, 318(23): 2306-2316.
[9] Fonkem E, Wong ET.NovoTTF-100A: a new treatment modality for recurrent glioblastoma[J]. Expert Rev Neurother, 2012, 12(8): 895-899.
[10] Davies AM, Weinberg U, Palti Y.Tumor treating fields: a new frontier in cancer therapy[J]. Ann N Y Acad Sci, 2013, 1291: 86-95.
[11] Gera N, Yang A, Holtzman TS, et al.Tumor treating fields perturb the localization of septins and cause aberrant mitotic exit[J]. PLoS One, 2015, 10(5): e0125269.
[12] Swanson KD, Lok E, Wong ET.An overview of alternating electric fields therapy (NovoTTF therapy) for the treatment of malignant glioma[J]. Curr Neurol Neurosci Rep, 2016, 16(1): 8-18.
[13] Giladi M, Schneiderman RS, Voloshin T, et al.Mitotic spindle disruption by alternating electric fields leads to improper chromosome segregation and mitotic catastrophe in cancer cells[J]. Sci Rep, 2015, 5: 18046.
[14] Arvind R, Chandana SR, Borad MJ, et al.Tumor-treating fields: a fourth modality in cancer treatment, new practice updates[J]. Crit Rev Oncol Hematol, 2021, 168: 103535.
[15] Benson L.Tumor treating fields technology: alternating electric field therapy for the treatment of solid tumors[J]. Semin Oncol Nurs, 2018, 34(2): 137-150.
[16] Voloshin T, Munster M, Blatt R, et al.Alternating electric fields (TTFields) in combination with paclitaxel are therapeutically effective against ovarian cancer cells in vitro and in vivo[J]. Int J Cancer, 2016, 139(12): 2850-2858.
[17] Wang L, Yan M, Wong CKC, et al.Microtubule-associated proteins (MAPs) in microtubule cytoskeletal dynamics and spermatogenesis[J]. Histol Histopathol, 2021, 36(3): 249-265.
[18] Felder CE, Prilusky J, Silman I, et al.A server and database for dipole moments of proteins[J]. Nucleic Acids Res, 2007, 35(Web Server issue): W512-521.
[19] Field CM, Coughlin M, Doberstein S, et al.Characterization of anillin mutants reveals essential roles in septin localization and plasma membrane integrity[J]. Development, 2005, 132(12): 2849-2860.
[20] Straight AF, Field CM, Mitchison TJ.Anillin binds nonmuscle myosin Ⅱ and regulates the contractile ring[J]. Mol Biol Cell, 2005, 16(1): 193-201.
[21] Iliaki S, Beyaert R, Afonina IS.Polo-like kinase 1 (PLK1) signaling in cancer and beyond[J]. Biochem Pharmacol, 2021, 193: 114747.
[22] Blatt R, Davidi S, Munster M, et al.In vivo safety of tumor treating fields (TTFields) applied to the torso[J]. Front Oncol, 2021, 11: 670809.
[23] Kirson ED, Giladi M, Gurvich Z, et al.Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs[J]. Clin Exp Metastasis, 2009, 26(7): 633-640.
[24] Hondroulis E, Melnick SJ, Zhang X, et al.Electrical field manipulation of cancer cell behavior monitored by whole cell biosensing device[J]. Biomed Microdevices, 2013, 15(4): 657-663.
[25] Ceresoli GL, Aerts JG, Dziadziuszko R, et al.Tumour treating fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): a multicentre, single-arm phase 2 trial[J]. Lancet Oncol, 2019, 20(12):1702-1709.
[26] Giladi M, Schneiderman RS, Porat Y, et al.Mitotic disruption and reduced clonogenicity of pancreatic cancer cells in vitro and in vivo by tumor treating fields[J]. Pancreatology, 2014, 14(1): 54-63.
[27] Kirson ED, Wasserman Y, Itzhaki A, et al. Modeling tumor growth kinetics and its implications for TTFields treatment planning[J]. Neuro-Oncol, 2010, 12(Suppl 4): iv36-iv57.
[28] Salzberg M, Kirson E, Palti Y, et al.A pilot study with very low-intensity, intermediate-frequency electric fields in patients with locally advanced and/or metastatic solid tumors[J]. Onkologie, 2008, 31(7): 362-365.
[29] Kirson ED, Schneiderman RS, Dbaly V, et al.Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields(TTFields)[J]. BMC Med Phys, 2009, 9: 1-13.
[30] Stupp R, Wong ET, Kanner AA, et al.NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase Ⅲ trial of a novel treatment modality[J]. Eur J Cancer, 2012, 48(14): 2192-2202.
[31] Kanner AA, Wong ET, Villano JL, et al.Post Hoc analyses of intention-to-treat population in phase Ⅲ comparison of NovoTTF-100A^TM system versus best physician's choice chemotherapy[J]. Semin Oncol, 2014, 41(Suppl 6): S25-S34.
[32] Toms SA, Kim CY, Nicholas G, et al.Increased compliance with tumor treating fields therapy is prognostic for improved survival in the treatment of glioblastoma: a subgroup analysis of the EF-14 phase Ⅲ trial[J]. J Neurooncol, 2019, 141(2): 467-473.
[33] Pless M, Droege C, von Moos R, et al. A phase Ⅰ/Ⅱ trial of tumor treating fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer[J]. Lung Cancer, 2013, 81(3): 445-450.
[34] Rivera F, Benavides M, Gallego J, et al.Tumor treating fields in combination with gemcitabine or gemcitabine plus nab-paclitaxel in pancreatic cancer: results of the PANOVA phase 2 study[J]. Pancreatology, 2019, 19(1): 64-72.
[35] Vergote I, von Moos R, Manso L, et al. Tumor Treating Fields in combination with paclitaxel in recurrent ovarian carcinoma: results of the INNOVATE pilot study[J]. Gynecol Oncol, 2018, 150(3): 471-477.
[36] Mrugala MM, Engelhard HH, Dinh Tran D, et al.Clinical practice experience with NovoTTF-100A^TM system for glioblastoma: the patient registry dataset(PRiDe)[J]. Semin Oncol, 2014, 41(Suppl 6): S4-S13.
[37] Chow LQM.Head and neck cancer[J]. N Engl J Med, 2020, 382(1): 60-72.

肿瘤治疗电场在头颈部癌症中的应用前景

Application prospect of tumor treating fields technology in head and neck cancer

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	程煜天, 徐乐, 马利, 吴海威, 陈占伟, 邹虎威, 张天奇, 刘桂军, 刘振兴, 尹长伟, 李文刚, 张世周, 黄圣运, 张东升. 头颈部腺样囊性癌预后分析：单中心经验[J]. 中国口腔颌面外科杂志, 2023, 21(5): 467-471.
[2]	王守鹏, 李胜男, 陈霖, 葛良玉, 李梦, 孟箭. ¹²⁵I放射性粒子植入治疗复发性腭部小唾液腺恶性肿瘤7例临床分析[J]. 中国口腔颌面外科杂志, 2023, 21(5): 497-501.
[3]	刘雨, 陈羽菱, 林云涛, 杨宏宇. MAP7D3在头颈部鳞状细胞癌中的作用探讨[J]. 中国口腔颌面外科杂志, 2023, 21(4): 352-359.
[4]	陈悦, 毛艳. 基于体验的护患协同设计在头颈部肿瘤术后患者家庭肠内营养中的应用[J]. 中国口腔颌面外科杂志, 2023, 21(4): 366-371.
[5]	李萍, 罗涛, 黄灿, 周驰, 孙宇. 口腔颌面-头颈恶性肿瘤术后急性肾损伤的发生率及危险因素分析[J]. 中国口腔颌面外科杂志, 2023, 21(4): 384-389.
[6]	向富萍, 侯黎莉, 杨玲, 王钰, 梁家青. 头颈部肿瘤患者术后发生谵妄危险因素的meta分析[J]. 中国口腔颌面外科杂志, 2023, 21(4): 407-412.
[7]	陈铭韬, 樊奇, 张陈平, 张志愿, 季彤, 任振虎. 65例头颈部恶性肿瘤根治术后急性肺血栓栓塞症临床分析[J]. 中国口腔颌面外科杂志, 2023, 21(3): 258-262.
[8]	韩林孜, 周建华, 赵谦, 董磊, 陈正岗, 邱建忠, 袁荣涛. 肿瘤相关成纤维细胞对头颈部鳞状细胞癌肿瘤浸润免疫细胞的调控作用及机制探讨[J]. 中国口腔颌面外科杂志, 2023, 21(2): 119-124.
[9]	邱银秀, 代天国, 徐波, 程进强, 刘忠龙. 重症口腔颌面头颈部多间隙感染临床分类探讨[J]. 中国口腔颌面外科杂志, 2023, 21(2): 125-130.
[10]	陈伟良. 延长垂直下斜方肌岛状肌皮瓣修复重建大型头颈部缺损[J]. 中国口腔颌面外科杂志, 2023, 21(1): 1-10.
[11]	李雪儿, 王正业, 买买提吐逊·吐尔地. 基于影像组学鉴定头颈部鳞状细胞癌患者HPV状态：诊断性meta分析[J]. 中国口腔颌面外科杂志, 2023, 21(1): 69-74.
[12]	龚霞, 李佳, 熊屏, 丁昂昂. 头颈部脉管肿瘤的超声诊断[J]. 中国口腔颌面外科杂志, 2022, 20(6): 521-526.
[13]	龚霞, 李佳, 熊屏, 丁昂昂. 头颈部脉管畸形的超声诊断[J]. 中国口腔颌面外科杂志, 2022, 20(5): 417-421.
[14]	杨慧丽, 王宇帆, 王锋, 沈月洪, 杨宏宇. NLRP1在头颈部鳞癌中的表达及预后意义[J]. 中国口腔颌面外科杂志, 2022, 20(5): 429-436.
[15]	王灿, 张春叶, 陶晓峰, 王博成, 朱凌. 29例头颈部炎性肌纤维母细胞肿瘤的CT及MRI影像学特征分析[J]. 中国口腔颌面外科杂志, 2022, 20(5): 494-499.