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

全脑光谱引导接受肿瘤治疗场的胶质母细胞瘤患者的换能器阵列的个性化映射

• 批准号: 10278480
• 负责人: Sanjeev Chawla
• 金额: $ 39.86万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10278480
• 关键词: Address; Adverse effects; Antimitotic Agents; Beds; Brain; Brain region; Cell Proliferation; Choline; Clinical; Computer Models; Diagnostic radiologic examination; Diffusion; Dose; Enrollment; Ensure; FDA approved; Glioblastoma; Goals; Image; Industrialization; Invaded; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Malignant Neoplasms; Malignant neoplasm of brain; Maps; Measures; Metabolic; Microscopic; Modality; Modeling; Multiparametric Analysis; N-acetylaspartate; Neurons; Outcome; Patient-Focused Outcomes; Patients; Perfusion; Positioning Attribute; Primary Brain Neoplasms; Prognosis; Proliferating; Protons; Quality of life; Radiation Injuries; Radiation therapy; Randomized; Recurrence; Reporting; Scalp structure; Solid; Spectrum Analysis; Therapeutic; Time; Transducers; arm; base; cancer cell; cell killing; chemoradiation; chemotherapeutic agent; clinical efficacy; clinical practice; contrast enhanced; design; dosimetry; electric field; follow-up; health related quality of life; imaging modality; improved; indexing; individual patient; industry partner; inter-individual variation; multimodality; neoplastic; neoplastic cell; neuroimaging; novel; optimal treatments; patient response; personalized diagnostics; personalized medicine; personalized therapeutic; profiles in patients; recruit; response; spectroscopic imaging; standard of care; survival outcome; temozolomide; tool; treatment arm; treatment comparison; treatment planning; treatment response; tumor; two-arm study

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

抽象的 胶质母细胞瘤 治疗。 发表 到 尽管有希望的临床结果，但很重要 （GBM）尽管具有侵略性的多模式 T UMOR治疗领域（TTFields）是最近批准的Loco区域和无创疗法 通过将换能器阵列放在靠近肿瘤的患者的剃光头皮上。已经找到了ttfields 改善GBM患者的生存结果，而不会对生活质量（QOL）造成任何不利影响。 治疗反应的个体间差异 ttfieldsis观察到。这是因为肿瘤的固体/对比度增强区域是针对ttfields的 在当前的临床实践中提供。这是高度不足的，因为GBM是极度渗透性的肿瘤 超出不可避免的复发的边缘，广泛入侵邻近的正常大脑区域 发生。在 细胞 经过 经过 递送 瘤 定位 剂量 和 胆碱/N-乙酰天冬氨酸 计算 患者 随机 ttfields 实验 大批 回复 结尾 将要 可以接受 范例 与传统的神经影像学，质子MR光谱衍生的胆碱（肿瘤指标）形成鲜明对比 增殖）可以更准确地检测隐匿性微观肿瘤。我们已经证明了 使用高级计算建模，可以将增加三倍的ttfield剂量提高到ttfields 重新调整传感器阵列的布局。在拟议的学术工业合作伙伴关系中，我们的目标是 通过精确映射，增强了TTFIELD剂量为整个可行的肿瘤床剂量 （精度诊断）以及随后通过优化的增强ttfield剂量输送 传感器阵列（个性化治疗学）。我们假设增强了Ttfields 肿瘤床将获得更有效的癌细胞杀伤，导致肿瘤复发延迟 这些患者的总生存率（OS）增加。衍生的全脑光谱成像（WBSI） 将使用地图来牙齿牙齿量。然后，精致 建模将用于设计传感器阵列的个性化放置。总共155 GBM 在接受护理标准疗法并愿意接受TTFields的治疗后，将被招募，并 在ttfields进行鉴定之前，将其分为两个治疗臂。对照组的患者（n = 77）将接受 基于仅由对比度增强定义的目标量（常规数组布局）和 ARM（n = 78）将根据胆碱异常定义的目标体积接收TTFields（替代 配置）。将从肿瘤床计算剂量测定参数以评估剂量临床 关系。进展时间（TTP）和OS将被视为基本和次级研究 分别分别。使用WBSI，扩散和灌注MR成像，一种组合的多参数方法 可以用来比较参加两个研究组的患者的治疗反应。最后，我们将建立 接受TTFIELD剂量增强的患者的QOL轮廓。如果成功，我们的研究将导致 通过制定个性化治疗计划，并改善了GBM患者的临床结果。 我