Response Assessment in Pediatric Neuro-Oncology: Implementation and Expansion of the RANO Criteria in a Randomized Phase II Trial of Pediatric Patients with Newly Diagnosed High-Grade Gliomas
Open Access
- 28 April 2016
- journal article
- research article
- Published by American Society of Neuroradiology (ASNR) in American Journal of Neuroradiology
- Vol. 37 (9), 1581-1587
- https://doi.org/10.3174/ajnr.a4782
Abstract
SUMMARY: 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.Keywords
This publication has 18 references indexed in Scilit:
- Bevacizumab plus Radiotherapy–Temozolomide for Newly Diagnosed GlioblastomaThe New England Journal of Medicine, 2014
- Challenges with defining response to antitumor agents in pediatric neuro-oncology: A report from the response assessment in pediatric neuro-oncology (RAPNO) working groupPediatric Blood & Cancer, 2013
- Response Assessment Criteria for Glioblastoma: Practical Adaptation and Implementation in Clinical Trials of Antiangiogenic TherapyCurrent Neurology and Neuroscience Reports, 2013
- Diffusion-weighted MR Imaging for the Differentiation of True Progression from Pseudoprogression Following Concomitant Radiotherapy with Temozolomide in Patients with Newly Diagnosed High-grade GliomasAcademic Radiology, 2012
- Analysis of the layering pattern of the apparent diffusion coefficient (ADC) for differentiation of radiation necrosis from tumour progressionEuropean Radiology, 2012
- Advanced MRI and PET imaging for assessment of treatment response in patients with gliomasThe Lancet Neurology, 2010
- Updated Response Assessment Criteria for High-Grade Gliomas: Response Assessment in Neuro-Oncology Working GroupJournal of Clinical Oncology, 2010
- Morphological and functional MRI, MRS, perfusion and diffusion changes after radiosurgery of brain metastasisEuropean Journal of Radiology, 2009
- Incidence of early pseudo‐progression in a cohort of malignant glioma patients treated with chemoirradiation with temozolomideCancer, 2008
- MGMT Promoter Methylation Status Can Predict the Incidence and Outcome of Pseudoprogression After Concomitant Radiochemotherapy in Newly Diagnosed Glioblastoma PatientsJournal of Clinical Oncology, 2008