Modified Criteria for Radiographic Response Assessment in Glioblastoma Clinical Trials

Ellingson, Benjamin M.; Wen, Patrick Y.; Cloughesy, Timothy F.

doi:10.1007/s13311-016-0507-6

Cited by 354 publications

(314 citation statements)

References 91 publications

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“…MRI is currently the most clinically useful imaging technique for patients with brain tumors (25,26), providing significantly better anatomic resolution than can be obtained with PET. Thus, we used precontrast and postcontrast MRI of glioma-bearing mice to generate contrast subtraction maps, a technique that our group has previously used to highlight relevant differences in GBM after various treatments (27).…”

Section: Resultsmentioning

confidence: 99%

Detection of immune responses after immunotherapy in glioblastoma using PET and MRI

Antonios

Soto

Everson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Contrast-enhanced MRI is typically used to follow treatment response and progression in patients with glioblastoma (GBM). However, differentiating tumor progression from pseudoprogression remains a clinical dilemma largely unmitigated by current advances in imaging techniques. Noninvasive imaging techniques capable of distinguishing these two conditions could play an important role in the clinical management of patients with GBM and other brain malignancies. We hypothesized that PET probes for deoxycytidine kinase (dCK) could be used to differentiate immune inflammatory responses from other sources of contrast-enhancement on MRI. Orthotopic malignant gliomas were established in syngeneic immunocompetent mice and then treated with dendritic cell (DC) vaccination and/or PD-1 mAb blockade. Mice were then imaged with [18F]-FAC PET/CT and MRI with i.v. contrast. The ratio of contrast enhancement on MRI to normalized PET probe uptake, which we term the immunotherapeutic response index, delineated specific regions of immune inflammatory activity. On postmortem examination, FACS-based enumeration of intracranial tumor-infiltrating lymphocytes directly correlated with quantitative [18F]-FAC PET probe uptake. Three patients with GBM undergoing treatment with tumor lysate-pulsed DC vaccination and PD-1 mAb blockade were also imaged before and after therapy using MRI and a clinical PET probe for dCK. Unlike in mice, [18F]-FAC is rapidly catabolized in humans; thus, we used another dCK PET probe, [18F]-clofarabine ([18F]-CFA), that may be more clinically relevant. Enhanced [18F]-CFA PET probe accumulation was identified in tumor and secondary lymphoid organs after immunotherapy. Our findings identify a noninvasive modality capable of imaging the host antitumor immune response against intracranial tumors.

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Section: Resultsmentioning

confidence: 99%

Detection of immune responses after immunotherapy in glioblastoma using PET and MRI

Antonios

Soto

Everson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Radionecrosis is a severe local tissue inflammatory reaction in response to radiotherapy [16] and shares considerable radiographic features with tumour recurrence [17]; there is often a combination of both entities [18] and such cases are notoriously difficult to diagnose and manage [17]. While revisions have been made to Response Assessment in Neuro-Oncology (RANO) criteria to standardise radiographic tumour monitoring [19], it remains challenging to accurately assess treatment-related effects from true tumour growth. In some cases, therapy is administered with the uncertainty of whether aggressive treatment is warranted, while other patients with true tumour progression are treated with a 'wait and see' approach rather than being switched to potentially life-extending treatment.…”

Section: Introductionmentioning

confidence: 99%

A comprehensive proteomic SWATH-MS workflow for profiling blood extracellular vesicles: a new avenue for glioma tumour surveillance

Hallal

Azimi

Wei

et al. 2020

Preprint

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There is a real need for biomarkers that can indicate glioma disease burden and inform clinical management, particularly in the recurrent glioblastoma (GBM; grade IV glioma) setting where treatment-associated brain changes can confound current and expensive tumour surveillance methods. In this regard, extracellular vesicles (EVs; 30-1000 nm membranous particles) hold major promise as robust tumour biomarkers. GBM-EVs encapsulate molecules that reflect the identity and molecular state of their cell-of-origin and cross the blood-brain-barrier into the periphery where they are readily accessible. Despite the suitability of circulating-EVs for GBM biomarker discovery, sample complexity has hindered comprehensive quantitative proteomic studies. Here, sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) was used in conjunction with a targeted data extraction strategy to comprehensively profile circulating-EVs isolated from plasma. Plasma-EVs sourced from pre-operative glioma II-IV patients (n=41) and controls (n=11) were sequenced by SWATH-MS, and the identities and absolute quantities of the proteins were extracted by aligning the SWATH-MS data against a custom glioma spectral library comprised of 8662 high confidence protein species. Overall, 4054 plasma-EV proteins were quantified across the cohorts, and putative circulating-EV biomarker proteins identified (adjusted p-value<0.05) included previously reported GBM-EV proteins identified in vitro and in neurosurgical aspirates. Principle component analyses showed that plasma-EV protein profiles clustered according to glioma subtype and WHO-grade, and plasma-EV proteins reflected the extent of glioma aggression. Using SWATH-MS, we describe the most comprehensive proteomic plasma-EV profiles for glioma and highlight the promise of this approach as an accurate and sensitive tumour monitoring method. Objective blood-based measurements of glioma tumour activity will support the implementation of next-generation, patient-centred therapies and are ideal surrogate endpoints for recurrent progression that would allow clinical trial protocols to be more dynamic and adapt to the individual patient and their cancer.

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“…Compounding this aggressive cancer phenotype are challenges in monitoring responses to treatment and tumor progression. While recent revisions to the Response Assessment in Neuro-Oncology (RANO) criteria helps to standardize glioma tumor monitoring [1] , radiographic measurements can be unreliable and insensitive to early signs of treatment failure and tumor relapse. Moreover, there are still difficulties deciphering pseudo-progression and pseudo-responses in some patients.…”

Section: Introductionmentioning

confidence: 99%

Deep sequencing of circulating exosomal microRNA allows non-invasive glioblastoma diagnosis

Ebrahimkhani

Vafaee

Hallal

et al. 2018

Preprint

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243; References, 36; Figure legends, 533. 32 ABSTRACT 34 Exosomes are nano-sized extracellular vesicles released by many cells that contain 35 molecules characteristic of their cell-of-origin, including microRNA. Exosomes released 36 by glioblastoma cross the blood-brain-barrier into the peripheral circulation, and carry 37 molecular cargo distinct to that of 'free-circulating' miRNA. In this pilot study, serum 38 exosomal-microRNAs were isolated from glioblastoma (n=12) patients and analyzed 39 using unbiased deep sequencing. Results were compared to sera from age-and gender-40 matched healthy controls, and to grades II-III (n=10) glioma patients. Significant 41 differentially expressed microRNAs were identified, and the predictive power of 42 individual and subsets of microRNAs were tested using univariate and multivariate 43 analyses. Additional sera from glioblastoma patients (n=4) and independent sets of 44 healthy (n=9) and non-glioma (n=10) controls were used to further test the specificity and 45 predictive power of this unique exosomal-microRNA signature. Twenty-six microRNAs 46 were differentially expressed in serum exosomes from glioblastoma patients' relative to 47 59

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Modified Criteria for Radiographic Response Assessment in Glioblastoma Clinical Trials

Cited by 354 publications

References 91 publications

Detection of immune responses after immunotherapy in glioblastoma using PET and MRI

Detection of immune responses after immunotherapy in glioblastoma using PET and MRI

A comprehensive proteomic SWATH-MS workflow for profiling blood extracellular vesicles: a new avenue for glioma tumour surveillance

Deep sequencing of circulating exosomal microRNA allows non-invasive glioblastoma diagnosis

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