The QIBA Profile for Dynamic Susceptibility Contrast MRI Quantitative Imaging Biomarkers for Assessing Gliomas.

The dynamic susceptibility contrast (DSC) MRI measures of relative cerebral blood volume (rCBV) play a central role in monitoring therapeutic response and disease progression in patients with gliomas. Previous investigations have demonstrated promise of using rCBV in classifying tumor grade, elucidating tumor viability after therapy, and differentiating pseudoprogression and pseudoresponse. However, the quantification and reproducibility of rCBV measurements across patients, devices, and software remain a critical barrier to routine or clinical trial use of longitudinal DSC MRI in patients with gliomas.

A Neuroradiologist's Guide to Operationalizing the Response Assessment in Neuro-Oncology (RANO) Criteria Version 2.0 for Gliomas in Adults.

Radiographic assessment plays a crucial role in the management of patients with central nervous system (CNS) tumors, aiding in treatment planning and evaluation of therapeutic efficacy by quantifying response. Recently, an updated version of the Response Assessment in Neuro-Oncology (RANO) criteria (RANO 2.0) was developed to improve upon prior criteria and provide an updated, standardized framework for assessing treatment response in clinical trials for gliomas in adults.

Assessing the Performance of Artificial Intelligence Models: Insights from the American Society of Functional Neuroradiology Artificial Intelligence Competition.

Background And Purpose: Artificial intelligence models in radiology are frequently developed and validated using data sets from a single institution and are rarely tested on independent, external data sets, raising questions about their generalizability and applicability in clinical practice. The American Society of Functional Neuroradiology (ASFNR) organized a multicenter artificial intelligence competition to evaluate the proficiency of developed models in identifying various pathologies on NCCT, assessing age-based normality and estimating medical urgency.

Materials And Methods: In total, 1201 anonymized, full-head NCCT clinical scans from 5 institutions were pooled to form the data set.

RANO 2.0: Update to the Response Assessment in Neuro-Oncology Criteria for High- and Low-Grade Gliomas in Adults.

Purpose: The Response Assessment in Neuro-Oncology (RANO) criteria for high-grade gliomas (RANO-HGG) and low-grade gliomas (RANO-LGG) were developed to improve reliability of response assessment in glioma trials. Over time, some limitations of these criteria were identified, and challenges emerged regarding integrating features of the modified RANO (mRANO) or the immunotherapy RANO (iRANO) criteria.

Methods: Informed by data from studies evaluating the different criteria, updates to the RANO criteria are proposed (RANO 2.

Early post-bevacizumab change in rCBV from DSC-MRI identifies pseudoresponse in recurrent glioblastoma: Results from ACRIN 6677/RTOG 0625.

Background: Progressive enhancement predicted poor survival in ACRIN 6677/RTOG 0625, a multi-center trial of bevacizumab with irinotecan or temozolomide in recurrent glioblastoma, but pseudoresponse likely limited enhancement-based survival prognostication in T1 non-progressors. We aimed to determine whether early change in cerebral blood volume from baseline (ΔCBV) could further stratify the T1 non-progressors according to overall (OS) and progression-free (PFS) survival.

Methods: 37/123 enrolled patients had DSC-MRI, including 13, 15, and 8 patients without 2D-T1 progression at 2, 8, and 16 weeks post-treatment initiation, respectively.

Value of dynamic contrast perfusion MRI to predict early response to bevacizumab in newly diagnosed glioblastoma: results from ACRIN 6686 multicenter trial.

Background: In Radiation Therapy Oncology Group (RTOG) 0825, a phase III trial of standard therapy with bevacizumab or without (placebo) in newly diagnosed glioblastoma, 44 patients underwent dynamic contrast enhanced (DCE) and/or dynamic susceptibility contrast (DSC) MRI in the American College of Radiology Imaging Network (ACRIN) trial 6686. The association between early changes in relative cerebral blood volume (rCBV) and volume transfer constant (Ktrans) with overall survival (OS) was evaluated.

Methods: MRI was performed at postop baseline (S0), immediately before (S1), 1 day after (S2), and 7 weeks after (S3) bevacizumab or placebo initiation.

Consensus recommendations for a dynamic susceptibility contrast MRI protocol for use in high-grade gliomas.

Despite the widespread clinical use of dynamic susceptibility contrast (DSC) MRI, DSC-MRI methodology has not been standardized, hindering its utilization for response assessment in multicenter trials. Recently, the DSC-MRI Standardization Subcommittee of the Jumpstarting Brain Tumor Drug Development Coalition issued an updated consensus DSC-MRI protocol compatible with the standardized brain tumor imaging protocol (BTIP) for high-grade gliomas that is increasingly used in the clinical setting and is the default MRI protocol for the National Clinical Trials Network. After reviewing the basis for controversy over DSC-MRI protocols, this paper provides evidence-based best practices for clinical DSC-MRI as determined by the Committee, including pulse sequence (gradient echo vs spin echo), BTIP-compliant contrast agent dosing (preload and bolus), flip angle (FA), echo time (TE), and post-processing leakage correction.

Consensus recommendations for a standardized brain tumor imaging protocol for clinical trials in brain metastases.

A recent meeting was held on March 22, 2019, among the FDA, clinical scientists, pharmaceutical and biotech companies, clinical trials cooperative groups, and patient advocacy groups to discuss challenges and potential solutions for increasing development of therapeutics for central nervous system metastases. A key issue identified at this meeting was the need for consistent tumor measurement for reliable tumor response assessment, including the first step of standardized image acquisition with an MRI protocol that could be implemented in multicenter studies aimed at testing new therapeutics. This document builds upon previous consensus recommendations for a standardized brain tumor imaging protocol (BTIP) in high-grade gliomas and defines a protocol for brain metastases (BTIP-BM) that addresses unique challenges associated with assessment of CNS metastases.

Interreader Variability of Dynamic Contrast-enhanced MRI of Recurrent Glioblastoma: The Multicenter ACRIN 6677/RTOG 0625 Study.

Purpose To evaluate factors contributing to interreader variation (IRV) in parameters measured at dynamic contrast material-enhanced (DCE) MRI in patients with glioblastoma who were participating in a multicenter trial. Materials and Methods A total of 18 patients (mean age, 57 years ± 13 [standard deviation]; 10 men) who volunteered for the advanced imaging arm of ACRIN 6677, a substudy of the RTOG 0625 clinical trial for recurrent glioblastoma treatment, underwent analyzable DCE MRI at one of four centers. The 78 imaging studies were analyzed centrally to derive the volume transfer constant (K) for gadolinium between blood plasma and tissue extravascular extracellular space, fractional volume of the extracellular extravascular space (v), and initial area under the gadolinium concentration curve (IAUGC).

ACRIN 6684: Multicenter, phase II assessment of tumor hypoxia in newly diagnosed glioblastoma using magnetic resonance spectroscopy.

A multi-center imaging trial by the American College of Radiology Imaging Network (ACRIN) "A Multicenter, phase II assessment of tumor hypoxia in glioblastoma using 18F Fluoromisonidazole (FMISO) with PET and MRI (ACRIN 6684)", was conducted to assess hypoxia in patients with glioblastoma (GBM). The aims of this study were to support the role of proton magnetic resonance spectroscopic imaging (1H MRSI) as a prognostic marker for brain tumor patients in multi-center clinical trials. Seventeen participants from four sites had analyzable 3D MRSI datasets acquired on Philips, GE or Siemens scanners at either 1.

Prognostic value of contrast enhancement and FLAIR for survival in newly diagnosed glioblastoma treated with and without bevacizumab: results from ACRIN 6686.

Background: ACRIN 6686/RTOG 0825 was a phase III trial of conventional chemoradiation plus adjuvant temozolomide with bevacizumab or without (placebo) in newly diagnosed glioblastoma. This study investigated whether changes in contrast-enhancing and fluid attenuated inversion recovery (FLAIR)-hyperintense tumor assessed by central reading prognosticate overall survival (OS).

Methods: Two hundred eighty-four patients (171 men; median age 57 y, range 19-79; 159 on bevacizumab) had MRI at post-op (baseline) and pre-cycle 4 of adjuvant temozolomide (22 wk post chemoradiation initiation).

ACRIN 6684: Assessment of Tumor Hypoxia in Newly Diagnosed Glioblastoma Using 18F-FMISO PET and MRI.

Purpose: Structural and functional alterations in tumor vasculature are thought to contribute to tumor hypoxia which is a primary driver of malignancy through its negative impact on the efficacy of radiation, immune surveillance, apoptosis, genomic stability, and accelerated angiogenesis. We performed a prospective, multicenter study to test the hypothesis that abnormal tumor vasculature and hypoxia, as measured with MRI and PET, will negatively impact survival in patients with newly diagnosed glioblastoma.

Experimental Design: Prior to the start of chemoradiation, patients with glioblastoma underwent MRI scans that included dynamic contrast enhanced and dynamic susceptibility contrast perfusion sequences to quantitate tumor cerebral blood volume/flow (CBV/CBF) and vascular permeability (k) as well as F-Fluoromisonidazole (F-FMISO) PET to quantitate tumor hypoxia.

Statistical Issues in Testing Conformance with the Quantitative Imaging Biomarker Alliance (QIBA) Profile Claims.

A major initiative of the Quantitative Imaging Biomarker Alliance is to develop standards-based documents called "Profiles," which describe one or more technical performance claims for a given imaging modality. The term "actor" denotes any entity (device, software, or person) whose performance must meet certain specifications for the claim to be met. The objective of this paper is to present the statistical issues in testing actors' conformance with the specifications.

Metrology Standards for Quantitative Imaging Biomarkers.

Although investigators in the imaging community have been active in developing and evaluating quantitative imaging biomarkers (QIBs), the development and implementation of QIBs have been hampered by the inconsistent or incorrect use of terminology or methods for technical performance and statistical concepts. Technical performance is an assessment of how a test performs in reference objects or subjects under controlled conditions. In this article, some of the relevant statistical concepts are reviewed, methods that can be used for evaluating and comparing QIBs are described, and some of the technical performance issues related to imaging biomarkers are discussed.

Consensus recommendations for a standardized Brain Tumor Imaging Protocol in clinical trials.

A recent joint meeting was held on January 30, 2014, with the US Food and Drug Administration (FDA), National Cancer Institute (NCI), clinical scientists, imaging experts, pharmaceutical and biotech companies, clinical trials cooperative groups, and patient advocate groups to discuss imaging endpoints for clinical trials in glioblastoma. This workshop developed a set of priorities and action items including the creation of a standardized MRI protocol for multicenter studies. The current document outlines consensus recommendations for a standardized Brain Tumor Imaging Protocol (BTIP), along with the scientific and practical justifications for these recommendations, resulting from a series of discussions between various experts involved in aspects of neuro-oncology neuroimaging for clinical trials.

Response assessment criteria for brain metastases: proposal from the RANO group.

CNS metastases are the most common cause of malignant brain tumours in adults. Historically, patients with brain metastases have been excluded from most clinical trials, but their inclusion is now becoming more common. The medical literature is difficult to interpret because of substantial variation in the response and progression criteria used across clinical trials.

Diffusion MRI quality control and functional diffusion map results in ACRIN 6677/RTOG 0625: a multicenter, randomized, phase II trial of bevacizumab and chemotherapy in recurrent glioblastoma.

Functional diffusion mapping (fDM) is a cancer imaging technique that quantifies voxelwise changes in apparent diffusion coefficient (ADC). Previous studies have shown value of fDMs in bevacizumab therapy for recurrent glioblastoma multiforme (GBM). The aim of the present study was to implement explicit criteria for diffusion MRI quality control and independently evaluate fDM performance in a multicenter clinical trial (RTOG 0625/ACRIN 6677).

Dynamic susceptibility contrast MRI measures of relative cerebral blood volume as a prognostic marker for overall survival in recurrent glioblastoma: results from the ACRIN 6677/RTOG 0625 multicenter trial.

Background: The study goal was to determine whether changes in relative cerebral blood volume (rCBV) derived from dynamic susceptibility contrast (DSC) MRI are predictive of overall survival (OS) in patients with recurrent glioblastoma multiforme (GBM) when measured 2, 8, and 16 weeks after treatment initiation.

Methods: Patients with recurrent GBM (37/123) enrolled in ACRIN 6677/RTOG 0625, a multicenter, randomized, phase II trial of bevacizumab with irinotecan or temozolomide, consented to DSC-MRI plus conventional MRI, 21 with DSC-MRI at baseline and at least 1 postbaseline scan. Contrast-enhancing regions of interest were determined semi-automatically using pre- and postcontrast T1-weighted images.

Quantitative imaging biomarkers: a review of statistical methods for computer algorithm comparisons.

Quantitative biomarkers from medical images are becoming important tools for clinical diagnosis, staging, monitoring, treatment planning, and development of new therapies. While there is a rich history of the development of quantitative imaging biomarker (QIB) techniques, little attention has been paid to the validation and comparison of the computer algorithms that implement the QIB measurements. In this paper we provide a framework for QIB algorithm comparisons.

A fully automatic extraction of magnetic resonance image features in glioblastoma patients.

Purpose: Glioblastoma is the most common malignant brain tumor. It is characterized by low median survival time and high survival variability. Survival prognosis for glioblastoma is very important for optimized treatment planning.

Early post-bevacizumab progression on contrast-enhanced MRI as a prognostic marker for overall survival in recurrent glioblastoma: results from the ACRIN 6677/RTOG 0625 Central Reader Study.

Background: RTOG 0625/ACRIN 6677 is a multicenter, randomized, phase II trial of bevacizumab with irinotecan or temozolomide in recurrent glioblastoma (GBM). This study investigated whether early posttreatment progression on FLAIR or postcontrast MRI assessed by central reading predicts overall survival (OS).

Methods: Of 123 enrolled patients, 107 had baseline and at least 1 posttreatment MRI.

Magnetic resonance spectroscopy as an early indicator of response to anti-angiogenic therapy in patients with recurrent glioblastoma: RTOG 0625/ACRIN 6677.

Background: The prognosis for patients with recurrent glioblastoma remains poor. The purpose of this study was to assess the potential role of MR spectroscopy as an early indicator of response to anti-angiogenic therapy.

Methods: Thirteen patients with recurrent glioblastoma were enrolled in RTOG 0625/ACRIN 6677, a prospective multicenter trial in which bevacizumab was used in combination with either temozolomide or irinotecan.