Whole-brain Spectroscopy Guided Personalized Mapping of Transducer Arrays for Glioblastoma Patients Receiving Tumor Treating Fields

摘要 胶质母细胞瘤 心理治疗。 投递 至 尽管临床结果很有希望，但意义重大 (GBM)是所有脑癌中最致命的，预后惨淡，尽管具有侵袭性的多模式 肿瘤治疗场(TTFields)是最近批准的一种局部非侵入性治疗 通过将传感器阵列放置在患者剃光的头皮上，靠近肿瘤。已找到TTfield 改善GBM患者的生存结果，而不会对生活质量(QOL)造成任何不良影响。 治疗反应的个体间差异性 TTFieldsis观察到。这是因为只有实体/对比度增强的肿瘤区域才是TTfield的目标 在目前的临床实践中分娩。这是非常不够的，因为基底节瘤是极具浸润性的肿瘤 广泛侵犯邻近的正常脑区，超出不可避免复发的边缘 发生。在……里面 蜂窝 通过 通过 投递 肿瘤 定位 剂量 使用 胆碱/N-乙酰天冬氨酸 计算型 病人 随机化 TTFields 试验性 数组 响应 结束 将要 可接受 范式 与传统的神经成像相比，质子磁共振波谱衍生出胆碱(一种肿瘤的指示物 增殖)可以更准确地检测隐蔽的微观肿瘤扩散。我们已经证明了 使用先进的计算模型，S有可能为肿瘤提供三倍增加的TTFields剂量 调整换能器阵列布局。在这项拟议的学术-产业合作伙伴关系中，我们的目标是 通过对这种浸润物的精确标测，增强TTFields对整个存活肿瘤床的剂量 (精确诊断)和后续交付通过优化的增强TTFields剂量 换能器阵列(个性化治疗)。我们假设增强的TTFields 到肿瘤病床将实现更有效的癌细胞杀灭，从而延缓肿瘤复发 提高了这些患者的总存活率(OS)。全脑光谱成像(WBSI) 将使用地图来识别目标卷。然后，世故的 建模将用于设计换能器阵列的个性化放置。总计155 GB 在接受标准护理治疗并愿意接受TTFields之后，将招募和 在TTFields启动之前分为两个治疗臂。对照组(n=77)的患者将接受 基于仅通过对比度增强定义的目标体积(常规阵列布局)和 ARM(n=78)将根据胆碱异常(交替)定义的目标体积接收TTfield 配置)。将从肿瘤病床计算剂量分布参数以评估剂量-临床 两性关系。进展时间(TTP)和操作系统将被视为主要和次要研究 分别得了分。使用WBSI、弥散和灌注磁共振成像，一种联合的多参数方法 用于比较两个研究组登记的患者的治疗反应。最后，我们将建立 接受增强型TTFields剂量的患者的生活质量概况。如果成功，我们的研究将导致 通过制定个性化的治疗计划，改善GBM患者的临床结果。 我

Abstract Glioblastoma therapy. delivered to Despite promising clinical outcomes, significant (GBM) is the deadliest of all brain cancers with a dismal prognosis despite aggressive multi-modal T umor treating fields (TTFields) are a recently approved loco-regional and noninvasive therapy by placing transducer arrays on patient's shaved scalp close to the tumor. TTFields have been found improve survival outcomes in GBM patients without causing any adverse effects on the quality of life (QoL). inter-individual variability in treatment response to TTFieldsis observed. This isbecause only solid/contrast enhancing regions of tumors are targeted for TTFields delivery in the current clinical practice. This is highly inadequate as GBMs are extremely infiltrative tumors that invade extensively into adjacent normal brain regions beyond enhancing margins where inevitable recurrence occurs. In cellular by by deliver tumor positioning dose with choline/N-acetylaspartate computational patients randomized TTFields experimental array response end will acceptable paradigm contrast to conventional neuroimaging, proton MR spectroscopy derived choline (an indicator of tumor proliferation) can detect occult microscopic tumor spread more accurately. We have demonstrated that using advanced computational modeling, it i s possible to deliver three-fold increased TTFields dose to t umors readjusting the layout of transducer arrays. In this proposed academic-industrial partnership, we aim to enhanced TTFields dose to the entire viable tumor bed by precise mapping of this i nfiltrative (precision diagnostics) and subsequent delivery of enhanced TTFields dose by optimized of transducer arrays (personalized therapeutics) . We hypothesize that enhanced TTFields to tumor beds will achieve more effective cancer cell killing resulting in delayed tumor recurrence increased overall survival (OS) of these patients. Whole brain spectroscopic imaging (WBSI) derived maps will be employed to dentify the target volume. Then, sophisticated modeling will be used to design personalized placement of transducer arrays. A total of 155 GBM after being treated with standard-of-care therapy and willing to receive TTFields will be recruited and into two treatment arms prior to i nitiation of TTFields. Patients in control arm (n=77) will receive based on target volume defined by contrast enhancement only (conventional array layout) and in arm (n=78) will receive TTFields based on target volume defined by choline abnormality (alternate configuration). Dosimetry profile parameters will be computed from tumor beds to assess dose-clinical relationships. Time to progression (TTP) and OS will be considered as primary and secondary study points, respectively. Using WBSI, diffusion and perfusion MR imaging, a combined multiparametric approach be utilized to compare treatment response from patients enrolled in two study arms. Lastly, we will establish QoL profile in patients receiving enhanced TTFields dose. If successful, our study will cause a shift by developing a personalized treatment plan with improved clinical outcomes of GBM patients. i