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首页> 美国卫生研究院文献>Neuro-Oncology >RBIO-07. TUMOR TREATING FIELDS (TTFIELDS) DELAY DNA DAMAGE REPAIR FOLLOWING RADIATION TREATMENT OF GLIOMA CELLS: IMPLICATIONS FOR IRRADIATION THROUGH TTFIELDS TRANSDUCER ARRAYS
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RBIO-07. TUMOR TREATING FIELDS (TTFIELDS) DELAY DNA DAMAGE REPAIR FOLLOWING RADIATION TREATMENT OF GLIOMA CELLS: IMPLICATIONS FOR IRRADIATION THROUGH TTFIELDS TRANSDUCER ARRAYS

机译：RBIO-07。胶质瘤细胞辐射治疗后的肿瘤治疗场（TTFIELDS）延迟DNA损伤修复：通过TTFIELDS传感器阵列进行辐射的意义

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The EF-14 clinical trial has demonstrated the effectiveness and safety of Tumor Treating Fields (TTFields) application using transducer arrays in patients with ndGBM, starting almost 4 months from diagnosis, during maintenance treatment with TMZ. In the past 3 years, several publications demonstrated that besides exerting anti-mitotic effects, TTFields can also inhibit DNA Damage Repair (DDR), thus leading to enhanced efficacy. Taken together with the fact that in most cancer types an earlier treatment start is favorable, applying TTFields in concomitant with radiotherapy (RT) shortly after diagnosis, has the potential to improve treatment outcome. The goal of the present work was to explore efficacy and safety aspects of TTFields application together with RT. The efficacy of TTFields application after RT was tested in glioma cells based on their survival rates. Effect on DDR was tested using the alkaline comet assay or by analyzing γH2AX or Rad51 foci formation and resolution. RT energy absorption by the transducer arrays was measured by applying RT doses of 2 Gy through the transducers placed on a solid-state phantom. Skin toxicities were tested in rats irradiated with 2 Gy, 5 times a week for 2 weeks through arrays placed on the dorsal skin. Applying TTFields shortly after irradiation, synergistically enhanced the effect of RT in glioma cells. Application of TTFields to irradiated cells impaired DDR, possibly by blocking homologous recombination. The presence of the transducer caused a minor reduction (<4%) in irradiation intensity at 20 mm and 60 mm below the arrays but led to a significant increase (344%) in irradiation dosage at the phantom surface. Transducer arrays on the rat skin during irradiation exposure did not lead to adverse skin reactions. Results support the application of TTFields therapy before and immediately after RT as a viable treatment regimen to enhance the outcome of RT.
机译：EF-14临床试验证明了使用换能器阵列在ndGBM患者中应用肿瘤治疗场（TTFields）的有效性和安全性，从诊断开始将近4个月，在TMZ维持治疗期间。在过去的三年中，一些出版物证明，TTFields除了发挥抗有丝分裂作用外，还可以抑制DNA损伤修复（DDR），从而提高疗效。结合大多数癌症类型中较早的治疗开始是有利的这一事实，在诊断后不久将TTFields与放射疗法（RT）结合使用，有可能改善治疗效果。当前工作的目的是探讨TTFields应用与RT的功效和安全性方面。根据其存活率，在神经胶质瘤细胞中测试了RT后TTFields的应用效果。使用碱性彗星试验或通过分析γH2AX或Rad51焦点形成和分离度来测试对DDR的影响。通过将2 Gy的RT剂量通过放置在固态体模上的换能器施加，来测量换能器阵列的RT能量吸收。通过放置在背侧皮肤上的阵列，对接受2 Gy照射的大鼠进行每周5次连续2周的皮肤毒性测试。照射后不久应用TTFields，可协同增强RT在神经胶质瘤细胞中的作用。将TTFields应用于受辐照的细胞会破坏DDR，可能是通过阻断同源重组来实现的。换能器的存在导致阵列下方20mm和60mm处的照射强度略有降低（<4％），但导致幻影表面的照射剂量显着增加（344％）。暴露于大鼠皮肤上的换能器阵列未导致不利的皮肤反应。结果支持TTFields治疗在RT之前和之后的应用，作为增强RT结局的可行治疗方案。

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