Blatt Roni, Davidi Shiri, Munster Mijal, Shteingauz Anna, Cahal Shay, Zeidan Adel, Marciano Tal, Bomzon Zeev, Haber Adi, Giladi Moshe, Weinberg Uri, Kinzel Adrian, Palti Yoram
Novocure Ltd, Haifa, Israel.
Novocure GmbH, Munich, Germany.
Front Oncol. 2021 Jun 24;11:670809. doi: 10.3389/fonc.2021.670809. eCollection 2021.
Tumor Treating Fields (TTFields) therapy is a non-invasive, loco-regional, anti-mitotic treatment modality that targets rapidly dividing cancerous cells, utilizing low intensity, alternating electric fields at cancer-cell-type specific frequencies. TTFields therapy is approved for the treatment of newly diagnosed and recurrent glioblastoma (GBM) in the US, Europe, Israel, Japan, and China. The favorable safety profile of TTFields in patients with GBM is partially attributed to the low rate of mitotic events in normal, quiescent brain cells. However, specific safety evaluations are warranted at locations with known high rates of cellular proliferation, such as the torso, which is a primary site of several of the most aggressive malignant tumors.
The safety of delivering TTFields to the torso of healthy rats at 150 or 200 kHz, which were previously identified as optimal frequencies for treating multiple torso cancers, was investigated. Throughout 2 weeks of TTFields application, animals underwent daily clinical examinations, and at treatment cessation blood samples and internal organs were examined. Computer simulations were performed to verify that the targeted internal organs of the torso were receiving TTFields at therapeutic intensities (≥ 1 V/cm root mean square, RMS).
No treatment-related mortality was observed. Furthermore, no significant differences were observed between the TTFields-treated and control animals for all examined safety parameters: activity level, food and water intake, stools, motor neurological status, respiration, weight, complete blood count, blood biochemistry, and pathological findings of internal organs. TTFields intensities of 1 to 2.5 V/cm RMS were confirmed for internal organs within the target region.
This research demonstrates the safety of therapeutic level TTFields at frequencies of 150 and 200 kHz when applied as monotherapy to the torso of healthy rats.
肿瘤治疗电场（TTFields）疗法是一种非侵入性的局部区域抗有丝分裂治疗方式，利用癌细胞类型特异性频率的低强度交变电场靶向快速分裂的癌细胞。TTFields疗法在美国、欧洲、以色列、日本和中国被批准用于治疗新诊断和复发性胶质母细胞瘤（GBM）。TTFields在GBM患者中良好的安全性部分归因于正常静止脑细胞中有丝分裂事件的发生率较低。然而，在已知细胞增殖率高的部位，如躯干（几种最具侵袭性恶性肿瘤的主要部位），进行特定的安全性评估是必要的。
研究了以150或200kHz（先前确定为治疗多种躯干癌症的最佳频率）向健康大鼠躯干施加TTFields的安全性。在应用TTFields的2周内，每天对动物进行临床检查，治疗结束时检查血液样本和内部器官。进行计算机模拟以验证躯干的目标内部器官是否接收到治疗强度（均方根，RMS≥1V/cm）的TTFields。
未观察到与治疗相关的死亡。此外，在所有检查的安全性参数方面，TTFields治疗组和对照组动物之间未观察到显著差异：活动水平、食物和水摄入量、粪便、运动神经状态、呼吸、体重、全血细胞计数、血液生化以及内部器官的病理结果。在目标区域内的内部器官中确认了1至2.5V/cm RMS的TTFields强度。
本研究证明了150和200kHz频率的治疗水平TTFields作为单一疗法应用于健康大鼠躯干时的安全性。
