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Principal Investigator: Manmeet Ahluwalia
Organization: UNIVERSITY OF WISCONSIN-MADISON
Fiscal Year: 2024
Award: $639,642
Funding agency: National Cancer Institute
ABSTRACT: Glioblastoma (GBM) has a complex infiltrating tumor microenvironment which extends well beyond
the visible enhancing tumor margins and plays a substantial role in GBM recurrence and poor outcomes.
Unfortunately, in the absence of a precise spatial map of tumor extent, it is often difficult to differentiate infiltrating
tumor from vasogenic edema on clinical MRI during radiation/surgical planning. The untreated infiltrating tumor
ultimately contributes to over 90% of GBM recurrences. An equally pressing challenge is the difficulty in
distinguishing recurrent tumor from treatment-effects following chemoradiation. Due to the histologically diverse
landscape of post-treated lesions, treatment-effects often co-exist with tumor recurrence, and mimic appearance
on imaging. In the absence of reliable tools, 15-20% of patients with GBM recurrence are incorrectly diagnosed
due to sampling error associated with intracranial biopsy. Thus, developing a non-invasive spatial map of
GBM tumor extent that can reliably identify infiltrating/recurrent tumor from confounding pathologies (treatment-
effects/edema), will have significant implications in radiation/surgical-planning and post-treatment management.
Recently, we developed a Radiomic-Image (Rad-I) map of tumor extent that uses computational features
corresponding to the micro-architectural image measurements of disorder in the local intensity gradients (i.e.,
gradient entropy). The initial version of the Rad-I map has been evaluated to distinguish recurrent tumors versus
treatment-effects on post-treatment Gd-T1w MRI with an 85% accuracy on n=75 studies, and to distinguish
infiltrating tumor versus vasogenic edema on pre-treatment MRI scans with a 94% accuracy on n=42 studies.
In this R01 project, we propose to improve on our initial version of Rad-I map by incorporating (1) additional
anatomical (T2w, FLAIR) and functional MR sequences (perfusion) and (2) a novel “lesion complexity” feature,
which captures organizational changes in the tissue composition via graph-theoretic approaches on MRI scans.
Overcoming limitations pertaining to small cohorts and lack of spatially mapped ex-vivo histology for validation,
Rad-I maps will be extensively validated on (1) a large multi-institutional MRI cohort with co-localized
histopathology and (2) the PRESERVE clinical trial designed to capture GBM heterogeneity via multiple co-
localized tissue samples/lesion. These cohorts will also allow for establishing associations of our new radiomic
features with underlying histological/molecular tumor characteristics- a prerequisite for clinical adoption. Lastly,
Rad-I maps will be evaluated within a tumor board survey to address the clinically challenging problem of
distinguishing recurrent tumors versus treatment effects. Criteria for success for Rad-I maps are that they are
at least non-inferior to the accuracy of stereotactic biopsies (85-90%) in identifying tumor niches corresponding
to (a) viable/infiltrating tumor vs. edema and (b) recurrent tumor vs. treatment effects. Multi-institutional validation
and end-user (tumor board) feedback will further confirm the utility of Rad-I maps as a noninvasive alternative to
surgical biopsies; thereby paving the way for radiation/surgical and post-treatment management in GBM tumors.
Terms: <3-D><3-Dimensional><3D><Address><Adoption><After Care><After-Treatment><Aftercare><Anatomic Sites><Anatomic structures><Anatomy><Appearance><Biopsy><Body Tissues><Brain Neoplasia><Brain Neoplasms><Brain Tumors><Cellularity><Characteristics><Clinical><Clinical Trials><Clinical Trials Design><Complex><Contrast-Enhancing Lesion><Development><Diagnosis><Disease><Disorder><Dropsy><Edema><Enhancing Lesion><Ensure><Entropy><Feedback><Gadolinium-Enhancing Lesion><Gd-Enhancing Lesion><General Radiology><Glioblastoma><Goals><Grade IV Astrocytic Neoplasm><Grade IV Astrocytic Tumor><Grade IV Astrocytoma><Graph><Heterogeneity><Histologic><Histologically><Histology><Histopathology><Hydrops><Image><Imaging Device><Imaging Instrument><Imaging Tool><Infiltration><Institution><Left><Lesion><Letters><MR Imaging><MR Tomography><MRI><MRI Scans><MRIs><Magnetic Resonance Imaging><Magnetic Resonance Imaging Scan><Maps><Measurement><Measures><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Molecular><Morphology><NMR Imaging><NMR Tomography><Neurosurgeon><Nuclear Magnetic Resonance Imaging><Operative Procedures><Operative Surgical Procedures><Organizational Change><Outcome><Pathology><Pathway interactions><Patients><Perfusion><Play><Radiation><Radiology><Radiology Specialty><Recurrence><Recurrent><Recurrent Neoplasm><Recurrent tumor><Reporting><Reproducibility><Resected><Role><Sampling><Sampling Errors><Scanning><Site><Surgical><Surgical Interventions><Surgical Procedure><Survey Instrument><Surveys><Tissue Sample><Tissues><Tumor Cell><Validation><Zeugmatography><cancer microenvironment><chemo-/radio-therapy><chemo-radio-therapy><chemo-radiotherapy><chemoradiation><chemoradiation therapy><chemoradiation treatment><chemoradiotherapy><clinical decision-making><clinical research site><clinical site><clinically actionable><cohort><cost effective><developmental><glioblastoma multiforme><imaging><improved><in vivo><innovate><innovation><innovative><multidisciplinary><neoplasm recurrence><neoplastic cell><neuro-surgeon><novel><pathway><post treatment><prospective><radio-chemo-therapy><radio-chemotherapy><radiochemotherapy><radiomics><response to therapy><response to treatment><social role><spongioblastoma multiforme><standard of care><success><surgery><therapeutic response><therapy response><three dimensional><tool><treatment effect><treatment response><treatment responsiveness><tumor><tumor microenvironment><tumors in the brain><validations><vasogenic edema>