Radiographic read paradigms and the roles of the central imaging laboratory in neuro-oncology clinical trials

Benjamin M Ellingson; Matthew S Brown; Jerrold L Boxerman; Elizabeth R Gerstner; Timothy J Kaufmann; Patricia E Cole; Jeffrey A Bacha; David Leung; Amy Barone; Howard Colman; Martin J van den Bent; Patrick Y Wen; W K Alfred Yung; Timothy F Cloughesy; Jonathan G Goldin

doi:10.1093/neuonc/noaa253

Radiographic read paradigms and the roles of the central imaging laboratory in neuro-oncology clinical trials

Neuro Oncol. 2021 Feb 25;23(2):189-198. doi: 10.1093/neuonc/noaa253.

Authors

Benjamin M Ellingson^{1

2

3

4}, Matthew S Brown^{1

2

5}, Jerrold L Boxerman⁶, Elizabeth R Gerstner⁷, Timothy J Kaufmann⁸, Patricia E Cole⁹, Jeffrey A Bacha¹⁰, David Leung¹¹, Amy Barone¹², Howard Colman¹³, Martin J van den Bent¹⁴, Patrick Y Wen¹⁵, W K Alfred Yung¹⁶, Timothy F Cloughesy^{4

17}, Jonathan G Goldin^{1

2

5}

Affiliations

¹ UCLA Brain Tumor Imaging Laboratory (BTIL), Center for Computer Vision and Imaging Biomarkers, University of California Los Angeles, Los Angeles, California, USA.
² Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
³ Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
⁴ UCLA Neuro-Oncology Program, University of California Los Angeles, Los Angeles, California, USA.
⁵ MedQIA, Los Angeles, California, USA.
⁶ Department of Diagnostic Imaging, Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA.
⁷ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁸ Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
⁹ Bayer Pharmaceuticals, Whippany, New Jersey, USA.
¹⁰ Edison Oncology Holding Corp, London, UK.
¹¹ Bristol Myers Squibb, New York, New York, USA.
¹² US Food and Drug Administration, Silver Spring, Maryland, USA.
¹³ Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA.
¹⁴ Department of Neuro-Oncology, Erasmus Medical Center Cancer Institute, Rotterdam, Netherlands.
¹⁵ Center for Neuro-Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
¹⁶ The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
¹⁷ Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.

Abstract

Determination of therapeutic benefit in intracranial tumors is intimately dependent on serial assessment of radiographic images. The Response Assessment in Neuro-Oncology (RANO) criteria were established in 2010 to provide an updated framework to better characterize tumor response to contemporary treatments. Since this initial update a number of RANO criteria have provided some basic principles for the interpretation of changes on MR images; however, the details of how to operationalize RANO and other criteria for use in clinical trials are ambiguous and not standardized. In this review article designed for the neuro-oncologist or treating clinician, we outline essential steps for performing radiographic assessments by highlighting primary features of the Imaging Charter (referred to as the Charter for the remainder of this article), a document that describes the clinical trial imaging methodology and methods to ensure operationalization of the Charter into the workings of a clinical trial. Lastly, we provide recommendations for specific changes to optimize this methodology for neuro-oncology, including image registration, requirement of growing tumor for eligibility in trials of recurrent tumor, standardized image acquisition guidelines, and hybrid reader paradigms that allow for both unbiased measurements and more comprehensive interpretation.

Keywords: Imaging Charter; RANO; clinical trials; imaging endpoints; neuro-oncology.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Brain Neoplasms* / diagnostic imaging
Brain Neoplasms* / therapy
Diagnostic Imaging
Humans
Laboratories*

Abstract

Publication types

MeSH terms

Grants and funding