Abstract
BACKGROUND AND PURPOSE: HERBY was a Phase II multicenter trial setup to establish the efficacy and safety of adding bevacizumab to radiation therapy and temozolomide in pediatric patients with newly diagnosed non–brain stem high-grade gliomas. This study evaluates the implementation of the radiologic aspects of HERBY.
MATERIALS AND METHODS: We analyzed multimodal imaging compliance rates and scan quality for participating sites, adjudication rates and reading times for the central review process, the influence of different Response Assessment in Neuro-Oncology criteria in the final response, the incidence of pseudoprogression, and the benefit of incorporating multimodal imaging into the decision process.
RESULTS: Multimodal imaging compliance rates were the following: diffusion, 82%; perfusion, 60%; and spectroscopy, 48%. Neuroradiologists' responses differed for 50% of scans, requiring adjudication, with a total average reading time per patient of approximately 3 hours. Pseudoprogression occurred in 10/116 (9%) cases, 8 in the radiation therapy/temozolomide arm and 2 in the bevacizumab arm (P < .01). Increased target enhancing lesion diameter was a reason for progression in 8/86 cases (9.3%) but never the only radiologic or clinical reason. Event-free survival was predicted earlier in 5/86 (5.8%) patients by multimodal imaging (diffusion, n = 4; perfusion, n = 1).
CONCLUSIONS: The addition of multimodal imaging to the response criteria modified the assessment in a small number of cases, determining progression earlier than structural imaging alone. Increased target lesion diameter, accounting for a large proportion of reading time, was never the only reason to designate disease progression.
ABBREVIATIONS:
- BEV
- bevacizumab
- CRRC
- Centralized Radiologic Review Committee
- EFS
- event-free survival
- HGG
- high-grade glioma
- MM
- multimodal
- RANO
- Response Assessment in Neuro-Oncology
- RT
- radiotherapy
- TMZ
- temolozomide
Footnotes
Disclosures: Daniel Rodriguez—RELATED: Grant: Hoffmann-La Roche, Comments: My post at Nottingham Universities Hospital Trust is funded by the HERBY trial, which was funded by Roche*; Support for Travel to Meetings for the Study or Other Purposes: Hoffmann-La Roche*; UNRELATED: Employment: Hoffmann-La Roche.* Tom Chambers—RELATED: Grant: Roche*; Support for Travel to Meetings for the Study or Other Purposes: Roche, Comments: Roche visited the image-analysis site*; UNRELATED: Employment: Nottingham National Health Service Trust. Monika Warmuth-Metz—RELATED: Consulting Fee or Honorarium: Roche, Comments: payment for imaging evaluation; Support for Travel to Meetings for the Study or Other Purposes: Roche; UNRELATED: Expert Testimony: Roche, Comments: payment for central review evaluation of imaging. Darren Hargrave—RELATED: Consulting Fee or Honorarium: F. Hoffmann-La Roche, Comments: This was not specific for this publication but in relation to the actual clinical trial; Support for Travel to Meetings for the Study or Other Purposes: F. Hoffmann-La Roche, Comments: This was not specific for this publication but in relation to the actual clinical trial; Provision of Writing Assistance, Medicines, Equipment, or Administrative Support: F. Hoffmann-La Roche, Comments: This was not specific for this publication but in relation to the actual clinical trial. Joseph Garcia—UNRELATED: Employment: Roche. Jacques Grill—RELATED: Grant: Hoffmann-La Roche, Comments: support for the trial and advisory board*; Support for Travel to Meetings for the Study or Other Purposes: F. Hoffmann-La Roche*; UNRELATED: Grants/Grants Pending: Roche, Bristol-Myers Squibb, Novartis.* Gudrun Zahlmann—UNRELATED: Employment: Hoffmann-La Roche. Paul S. Morgan—RELATED: Grant: F. Hoffmann-La Roche*; Support for Travel to Meetings for the Study or Other Purposes: F. Hoffmann-La Roche*; UNRELATED: Employment: Nottingham University Hospitals.* Tim Jaspan—RELATED: Grant: Nottingham University Hospitals National Health Service Trust*; Support for Travel to Meetings for the Study or Other Purposes: University Hospitals National Health Service Trust*; UNRELATED: Employment: Nottingham University Hospitals National Health Service Trust.* Raphael Calmon—RELATED: Support for Travel to Meetings for the Study or Other Purposes: F. Hoffmann-La Roche; Fees for Participation in Review Activities such as Data Monitoring Boards, Statistical Analysis, Endpoint Committees, and the like: F. Hoffman-La Roche. *Money paid to the institution.
This study was funded by F. Hoffmann-La Roche Ltd (study number BO25041; clinicaltrials.gov NCT01390948). All research at Great Ormond Street Hospital National Health Service Foundation Trust and University College London Great Ormond Street Institute of Child Health is made possible by the National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre.
The views expressed are those of the authors and are not necessarily those of the National Health Service, the National Institute for Health Research, or the Department of Health.
Previously presented in part at: International Symposium on Pediatric Neuro-Oncology, June 29 to July 3, 2018; Denver, Colorado.
- © 2019 by American Journal of Neuroradiology
