The coalition’s Brain Tumor Imaging Standardization Steering Committee published its recommended standards, called the Brain Tumor Imaging Protocol (BTIP), in the advanced access online edition of the journal Neuro-Oncology.
As in all oncology trials, overall survival (OS) is the “gold standard” of measuring investigational brain tumor therapies’ effectiveness. However, because OS trials are lengthy and expensive, investigators are looking to use alternative endpoints via imaging to measure tumor progression and response to determine the relative value of an investigational treatment.
The coalition hopes that the development and adoption of a standardized MRI protocol in brain tumor clinical trials will help validate and build confidence in the use of quantitative imaging surrogates as endpoints for drugs seeking FDA approval. A standardized protocol could also incentivize brain tumor drug development by providing an accepted way to capture imaging data essential to evaluating new treatments.
“Malignant brain tumors, particularly glioblastomas, are some of the most complex and treatment-resistant cancers,” said Dr. Mark Gilbert, MD, chair of the Brain Tumor Imaging Standardization Steering Committee and chief of the Neuro-Oncology Branch of the National Cancer Institute. “Glioblastoma patients have a median survival of only 14-16 months, and fewer than 10 percent survive beyond five years of their diagnosis. With limited treatment options available, there is a critical need to quickly identify new, effective therapies for this patient population.”
Traditionally, response and progression are measured in neuro-oncology using MR imaging. However, there have been issues with variability in the interpretation of images and tumor measurements between observers and between treatment centers. The lack of standards in MR imaging acquisition protocols and differences in MR scanners has limited the ability to combine imaging data across sites in a multicenter clinical trial study.
“It is well known that even minor differences in hardware or sequence timing may result in significant changes in image contrast,” said Benjamin Ellingson, PhD, of the Department of Radiological Sciences at the David Geffen School of Medicine at UCLA and lead author of the BTIP paper. “Moreover, a variety of MR protocols are commonly used for the same purpose, further hindering interpretation of imaging results from different treatment centers in the absence of tight control and standardization of image acquisition parameters.”
A meeting was convened by the JBTDDC in 2014 with the U.S. Food and Drug Administration, National Cancer Institute, clinical scientists, imaging experts, pharmaceutical and biotech companies, clinical trial cooperative groups, and patient advocacy groups to improve the accuracy of determining true response to a particular therapy and minimize errors in brain tumor clinical trials.
“During our participation in the Brain Tumor Endpoints Workshop, we identified standardization of imaging data acquisition and analysis as a step towards increasing the reliability of radiographic endpoints in brain tumor clinical trials, and improving the ability to assess the impact of therapies in neuro-oncology,” said Richard Pazdur, MD, director of the FDA’s Office of Hematology and Oncology Products.
The protocol is designed to minimize patient burden and has taken into account the different capabilities of imaging instruments across international medical centers.
The next phase of the group's effort is to achieve field-wide clinical trial adoption and use of the protocol, and the JBTDDC is actively requesting from major US and European neuro-oncology clinical trial co-operative groups, as well as biopharmaceutical sponsors, the incorporation of the protocol as the standard for use in their future brain tumor clinical trials.