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Standardized MRI assessment of high-grade glioma response: a review of the essential elements and pitfalls of the RANO criteria.

ABSTRACT: Accurately evaluating response in the treatment of high-grade gliomas presents considerable challenges. This review looks at the advancements made in response criteria while critically outlining remaining weaknesses, and directs our vision toward promising endpoints to come. The 2010 guidelines from the Response Assessment in Neuro-Oncology (RANO) working group have enhanced interpretation of clinical trials involving novel treatments for high-grade glioma. Yet, while the criteria are considered clinically applicable to high-grade glioma trials, as well as reasonably accurate and reproducible, RANO lacks sufficient detail for consistent implementation in certain aspects and leaves some issues from the original Macdonald guidelines unresolved. To provide the most accurate assessment of response to therapeutic intervention currently possible, it is essential that trial oncologists and radiologists not only have a solid understanding of RANO guidelines, but also proper insight into the inherent limitations of the criteria. With the expectation of improved data collection as a standard, the author anticipates that the next high-grade glioma response criteria updates will incorporate advanced MRI methods and quantitative tumor volume measurements, availing a more accurate interpretation of response in the future.

SUBMITTER: Yang D

PROVIDER: S-EPMC6760341 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Standardized MRI assessment of high-grade glioma response: a review of the essential elements and pitfalls of the RANO criteria.

Yang Dewen D

Neuro-oncology practice 20150712 1

Accurately evaluating response in the treatment of high-grade gliomas presents considerable challenges. This review looks at the advancements made in response criteria while critically outlining remaining weaknesses, and directs our vision toward promising endpoints to come. The 2010 guidelines from the Response Assessment in Neuro-Oncology (RANO) working group have enhanced interpretation of clinical trials involving novel treatments for high-grade glioma. Yet, while the criteria are considered ...[more]

PMID: 31579522

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Project description:Determination of tumor response to treatment in neuro-oncology is challenging, particularly when antiangiogenic agents are considered. Nontumoral factors (eg, blood-brain barrier disruption, edema, and necrosis) can alter contrast enhancement independent of true tumor response/progression. Furthermore, gliomas are often infiltrative, with nonenhancing components. In adults, the Response Assessment in Neuro-Oncology (RANO) criteria attempted to address these issues. No such guidelines exist yet for children. The ongoing randomized phase II trial, A Study of Avastin (bevacizumab) in Combination With Temolozomide (TMZ) and Radiotherapy in Paediatric and Adolescent Patients With High-Grade Glioma (HERBY), will establish the efficacy and safety of the antiangiogenic agent bevacizumab for the first-line treatment of newly diagnosed high-grade glioma in children (n = 121 patients, enrollment complete). The primary end point is event-free survival (tumor progression/recurrence by central review, second primary malignancy, or death). Determination of progression or response is based on predefined clinical and radiographic criteria, modeled on the RANO criteria and supported by expert pseudoprogression review and the use of standardized imaging protocols. The HERBY trial will also compare conventional MR imaging (T1-weighted and T2/fluid-attenuated inversion recovery sequences) with conventional MR imaging plus diffusion/perfusion imaging for response assessment. It is anticipated that HERBY will provide new insights into antiangiogenic-treated pediatric brain tumors. HERBY will also investigate the practicality of obtaining adequate quality diffusion/perfusion scans in a trial setting, and the feasibility of implementing standard imaging protocols across multiple sites. To date, 61/73 (83.6%) patients with available data have completed diffusion-weighted imaging (uptake of other nonconventional techniques has been limited). Harmonization of imaging protocols and techniques may improve the robustness of pediatric neuro-oncology studies and aid future trial comparability.

Project description:PurposeThis prospective study evaluated the use of vascular, extracellular and restricted diffusion for cytometry in tumours (VERDICT) MRI to investigate the tissue microstructure in glioma. VERDICT-derived parameters were correlated with both histological features and tumour subtype and were also used to explore the peritumoural region.MethodsFourteen consecutive treatment-naïve patients (43.5 years ± 15.1 years, six males, eight females) with suspected glioma underwent diffusion-weighted imaging including VERDICT modelling. Tumour cell radius and intracellular and combined extracellular/vascular volumes were estimated using a framework based on linearisation and convex optimisation. An experienced neuroradiologist outlined the peritumoural oedema, enhancing tumour and necrosis on T2-weighted imaging and contrast-enhanced T1-weighted imaging. The same regions of interest were applied to the co-registered VERDICT maps to calculate the microstructure parameters. Pathology sections were analysed with semi-automated software to measure cellularity and cell size.ResultsVERDICT parameters were successfully calculated in all patients. The imaging-derived results showed a larger intracellular volume fraction in high-grade glioma compared to low-grade glioma (0.13 ± 0.07 vs. 0.08 ± 0.02, respectively; p = 0.05) and a trend towards a smaller extracellular/vascular volume fraction (0.88 ± 0.07 vs. 0.92 ± 0.04, respectively; p = 0.10). The conventional apparent diffusion coefficient was higher in low-grade gliomas compared to high-grade gliomas, but this difference was not statistically significant (1.22 ± 0.13 × 10-3 mm2/s vs. 0.98 ± 0.38 × 10-3 mm2/s, respectively; p = 0.18).ConclusionThis feasibility study demonstrated that VERDICT MRI can be used to explore the tissue microstructure of glioma using an abbreviated protocol. The VERDICT parameters of tissue structure correlated with those derived on histology. The method shows promise as a potential test for diagnostic stratification and treatment response monitoring in the future.Key points• VERDICT MRI is an advanced diffusion technique which has been correlated with histopathological findings obtained at surgery from patients with glioma in this study. • The intracellular volume fraction measured with VERDICT was larger in high-grade tumours compared to that in low-grade tumours. • The results were complementary to measurements from conventional diffusion-weighted imaging, and the technique could be performed in a clinically feasible timescale.

Dataset Information

Standardized MRI assessment of high-grade glioma response: a review of the essential elements and pitfalls of the RANO criteria.

Publications

Standardized MRI assessment of high-grade glioma response: a review of the essential elements and pitfalls of the RANO criteria.

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