Document text
Principal Investigator: Sanjeev Chawla
Organization: UNIVERSITY OF PENNSYLVANIA
Fiscal Year: 2024
Award: $372,319
Funding agency: National Cancer Institute
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
Terms: <2-arm study><Active Follow-up><Address><Adverse effects><Antimitotic Agents><Antimitotic Drugs><Antimitotics><Beds><Brain><Brain Cancer><Brain Nervous System><Brain region><Cancers><Cell Growth in Number><Cell Multiplication><Cell Proliferation><Cellular Proliferation><Choline><Clinical><Clinical Trials><Computer Models><Computerized Models><Diffusion><Dose><Encephalon><Ensure><FDA approved><Glioblastoma><Goals><Grade IV Astrocytic Neoplasm><Grade IV Astrocytic Tumor><Grade IV Astrocytoma><H+ element><Hydrogen Ions><Image><Immune mediated therapy><Immunologically Directed Therapy><Immunotherapy><Industrialization><MR Imaging><MR Spectroscopy><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Magnetic Resonance Spectroscopy><Malignant Cell><Malignant Neoplasms><Malignant Tumor><Malignant Tumor of the Brain><Malignant neoplasm of brain><Maps><Measures><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Metabolic><Methods><Microscopic><Microtubular Function Inhibitors><Mitosis Inhibitor Agents><Mitosis Inhibitor Drugs><Mitosis Inhibitors><Mitotic Inhibitor Agents><Mitotic Inhibitor Drugs><Mitotic Inhibitors><Modality><Modeling><Multiparametric Analysis><N-acetyl aspartate><N-acetyl-L-aspartate><N-acetylaspartate><NMR Imaging><NMR Tomography><Nerve Cells><Nerve Unit><Neural Cell><Neurocyte><Neurons><Nuclear Magnetic Resonance Imaging><Outcome><Parameter Estimation><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Perfusion><Position><Positioning Attribute><Primary Brain Neoplasms><Primary Brain Tumors><Prognosis><Proliferating><Protons><QOL><Quality of life><Radiation Injuries><Radiation therapy><Radiography><Radiotherapeutics><Radiotherapy><Randomized><Recurrence><Recurrent><Recurrent Neoplasm><Recurrent tumor><Reporting><Roentgenography><Scalp><Scalp structure><Solid><Spectroscopy><Spectrum Analyses><Spectrum Analysis><Temodal><Temodar><Therapeutic><Time><Transducers><Tumor Cell><Tumor Cell Invasion><Tumor Invasion><Zeugmatography><active followup><arm><cancer cell><cell killing><chemo-/radio-therapy><chemo-radio-therapy><chemo-radiotherapy><chemoradiation><chemoradiation therapy><chemoradiation treatment><chemoradiotherapy><chemotherapeutic agent><clinical efficacy><clinical practice><compare treatment><computational modeling><computational models><computer based models><computerized modeling><contrast enhanced><design><designing><diffused><diffuses><diffusing><diffusions><dosimetry><electric field><follow up><follow-up><followed up><followup><glioblastoma multiforme><health related quality of life><image-based method><imaging><imaging method><imaging modality><imaging spectroscopy><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based therapies><immune-based treatments><immuno therapy><improved><indexing><individual patient><individualized therapeutic><industrial partnership><industry partner><industry partnership><inter-individual variability><inter-individual variation><interindividual variability><interindividual variation><intervention arm><irradiation injury><malignancy><methazolastone><multi-modality><multimodality><neoplasm recurrence><neoplasm/cancer><neoplastic><neoplastic cell><neural imaging><neuro-imaging><neuroimaging><neurological imaging><neuronal><novel><optimal therapies><optimal treatments><participant enrollment><patient enrollment><patient oriented outcomes><patient profile><patient response><patient specific response><personalization of treatment><personalized diagnosis><personalized diagnostics><personalized medicine><personalized therapeutic><personalized therapy><personalized treatment><precise diagnostics><precision diagnostics><profiles in patients><radiation treatment><radio-chemo-therapy><radio-chemotherapy><radiochemotherapy><radiologic imaging><radiological imaging><randomisation><randomization><randomly assigned><recruit><response><response to therapy><response to treatment><responsive patient><spectroscopic imaging><spongioblastoma multiforme><standard of care><survival outcome><temozolomide><therapeutic response><therapy response><tool><treatment arm><treatment comparison><treatment planning><treatment response><treatment responsiveness><treatment with radiation><tumor><two-arm study>