Glas Martin, Ballo Matthew T, Bomzon Ze'ev, Urman Noa, Levi Shay, Lavy-Shahaf Gitit, Jeyapalan Suriya, Sio Terence T, DeRose Paul M, Misch Martin, Taillibert Sophie, Ram Zvi, Hottinger Andreas F, Easaw Jacob, Kim Chae-Yong, Mohan Suyash, Stupp Roger
Division of Clinical Neurooncology, Department of Neurology and German Cancer Consortium (DKTK) Partner Site, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Department of Radiation Oncology, West Cancer Center and Research Institute, Memphis, Tennessee.
Int J Radiat Oncol Biol Phys. 2022 Apr 1;112(5):1269-1278. doi: 10.1016/j.ijrobp.2021.12.152. Epub 2021 Dec 26.
Tumor-treating fields (TTFields) are an antimitotic treatment modality that interfere with glioblastoma (GBM) cell division and organelle assembly by delivering low-intensity, alternating electric fields to the tumor. A previous analysis from the pivotal EF-14 trial demonstrated a clear correlation between TTFields dose density at the tumor bed and survival in patients treated with TTFields. This study tests the hypothesis that the antimitotic effects of TTFields result in measurable changes in the location and patterns of progression of newly diagnosed GBM.
Magnetic resonance images of 428 newly diagnosed GBM patients who participated in the pivotal EF-14 trial were reviewed, and the rates at which distant progression occurred in the TTFields treatment and control arm were compared. Realistic head models of 252 TTFields-treated patients were created, and TTFields intensity distributions were calculated using a finite element method. The TTFields dose was calculated within regions of the tumor bed and normal brain, and its relationship with progression was determined.
Distant progression was frequently observed in the TTFields-treated arm, and distant lesions in the TTFields-treated arm appeared at greater distances from the primary lesion than in the control arm. Distant progression correlated with improved clinical outcome in the TTFields patients, with no such correlation observed in the controls. Areas of normal brain that remained normal were exposed to higher TTFields doses compared with normal brain that subsequently exhibited neoplastic progression. Additionally, the average dose to areas of the enhancing tumor that returned to normal was significantly higher than in the areas of the normal brain that progressed to enhancing tumor.
There was a direct correlation between TTFields dose distribution and tumor response, confirming the therapeutic activity of TTFields and the rationale for optimizing array placement to maximize the TTFields dose in areas at highest risk of progression, as well as array layout adaptation after progression.
肿瘤治疗电场（TTFields）是一种抗有丝分裂治疗方式，通过向肿瘤传递低强度交变电场来干扰胶质母细胞瘤（GBM）细胞分裂和细胞器组装。关键的EF - 14试验之前的一项分析表明，肿瘤床处的TTFields剂量密度与接受TTFields治疗的患者生存率之间存在明显相关性。本研究检验以下假设：TTFields的抗有丝分裂作用会导致新诊断GBM的进展位置和模式发生可测量的变化。
回顾了参与关键EF - 14试验的428例新诊断GBM患者的磁共振图像，并比较了TTFields治疗组和对照组远处进展的发生率。创建了252例接受TTFields治疗患者的逼真头部模型，并使用有限元方法计算TTFields强度分布。计算肿瘤床和正常脑区域内的TTFields剂量，并确定其与进展的关系。
在接受TTFields治疗的组中经常观察到远处进展，与对照组相比，接受TTFields治疗的组中的远处病变出现在距原发病变更远的位置。远处进展与TTFields治疗患者更好的临床结果相关，而在对照组中未观察到这种相关性。与随后出现肿瘤进展的正常脑相比，保持正常的正常脑区域暴露于更高的TTFields剂量。此外，恢复正常的增强肿瘤区域的平均剂量显著高于进展为增强肿瘤的正常脑区域。
TTFields剂量分布与肿瘤反应之间存在直接相关性，证实了TTFields的治疗活性以及优化阵列放置以在进展风险最高的区域最大化TTFields剂量的原理，以及进展后调整阵列布局的原理。
