Whole-brain Spectroscopy Guided Personalized Mapping of Transducer Arrays for Glioblastoma Patients Receiving Tumor Treating Fields
Whole-brain Spectroscopy Guided Personalized Mapping of Transducer Arrays for Glioblastoma Patients Receiving Tumor Treating Fields
批准号:
10278480
负责人:
Sanjeev Chawla
金额:
$39.86万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
未结题
起止时间:
2021-09-01 至 2026-05-31
关键词:
AddressAdverse effectsAntimitotic AgentsBedsBrainBrain regionCell ProliferationCholineClinicalComputer ModelsDiagnostic radiologic examinationDiffusionDoseEnrollmentEnsureFDA approvedGlioblastomaGoalsImageIndustrializationInvadedMagnetic Resonance ImagingMagnetic Resonance SpectroscopyMalignant NeoplasmsMalignant neoplasm of brainMapsMeasuresMetabolicMicroscopicModalityModelingMultiparametric AnalysisN-acetylaspartateNeuronsOutcomePatient-Focused OutcomesPatientsPerfusionPositioning AttributePrimary Brain NeoplasmsPrognosisProliferatingProtonsQuality of lifeRadiation InjuriesRadiation therapyRandomizedRecurrenceReportingScalp structureSolidSpectrum AnalysisTherapeuticTimeTransducersarmbasecancer cellcell killingchemoradiationchemotherapeutic agentclinical efficacyclinical practicecontrast enhanceddesigndosimetryelectric fieldfollow-uphealth related quality of lifeimaging modalityimprovedindexingindividual patientindustry partnerinter-individual variationmultimodalityneoplasticneoplastic cellneuroimagingnoveloptimal treatmentspatient responsepersonalized diagnosticspersonalized medicinepersonalized therapeuticprofiles in patientsrecruitresponsespectroscopic imagingstandard of caresurvival outcometemozolomidetooltreatment armtreatment comparisontreatment planningtreatment responsetumortwo-arm study
中文摘要
摘要
英文摘要
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
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