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

摘要

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