NCI Merit Grant Awarded for Brain Cancer Adaptive Therapy Study

A Sylvester Comprehensive Cancer Center researcher has been awarded a $5 million seven-year grant from the National Cancer Institute (NCI) to study how advanced imaging during treatment may be used to improve radiation therapy for patients with glioblastoma, a deadly brain tumor.

“Glioblastoma is the most common cancer originating in the brain with an average survival of only 18-24 months,”  said Eric A. Mellon, MD, PhD, associate professor of radiation oncology and biomedical engineering at the University of Miami Miller School of Medicine, and co-leader of Sylvester’s Neurologic Cancer Site Disease Group. “Our goal is to identify glioblastoma patients who are failing radiation therapy during treatment and implement aggressive second-line treatments to improve survival.”

An experienced specialist in the use of magnetic resonance imaging (MRI) for brain cancers, Dr. Mellon is the principal investigator for the study, “A Physiologic Adaptive Radiation Therapy Pipeline for Glioblastoma by Daily Multiparametric MRI and Machine Learning.” Dr. Mellon received the highly competitive National Cancer Institute R37 Method to Extend Research in Time (MERIT) award after his project grant scored among the best in e nation. The MERIT award provides early-stage investigators with five years of research funding and eligibility to extend their grant an extra two years.

Dr. Mellon aims to enroll 100 glioblastoma patients in the study using MRIdian, an advanced technology developed by ViewRay, Inc., that combines daily MRI with radiation therapy. This leading-edge technology, now in active use at Sylvester, will allow Dr. Mellon to conduct daily assessments of brain, cavity caused by the surgical removal of the tumor, and any unremovable tumor.

“The findings from our study will help radiation oncologists deliver the most effective personalized care for glioblastoma patients,” he said. “Our study may also have important applications for treating other types of tumors.”

Glioblastoma radiation therapy is typically given over six weeks with chemotherapy. Other radiation machines used for treatment of glioblastoma are incapable of seeing changes during treatment, Dr. Mellon said. Most centers only get MRI scans before treatment and after treatment, so the changes that often occur during treatment are ignored, he added.

To improve the ability of physicians to respond to changes during treatment, the MRIdian system uses several different types of daily MRI. Dr. Mellon seeks to determine whether a cancer is continuing to grow despite treatment or if there is “pseudo-progression” characterized by tumor inflammation. Images will be processed by machine learning and radiomics techniques to help clinicians predict the outcome — an important consideration as patients whose tumors do respond often live for years, rather than an average of less than nine months for patients whose tumors are not responding.

“We will apply MRI to analyze the physiology of the tumor, including the diffusion of water molecules, the amount of blood flow and the metabolic compounds in the tissues,” Dr. Mellon said. “Tumors typically have a higher cellular density than normal tissue, limiting the ability of water molecules to move around. They also require large amounts of blood and produce certain metabolites associated with highly active cellular processes. These processes change during treatment depending on tumor response.”

Noting that UM and ViewRay have an ongoing academic-industry partnership to improve brain tumor imaging techniques and technology, Dr. Mellon said, “There are many other things that we can learn from this study. For instance, we can track whether changes are occurring at the beginning, middle or end of the treatment period. We are also adjusting the radiation fields to match shrinking tumors and reducing the area of the brain receiving treatment to reduce side effects.”

Dr. Mellon said findings from the NCI-funded study at Sylvester can be distributed to more than 60 MRIdian centers, supporting future multi-institutional trials of early radiation therapy dose escalation to improve the survival of patients with poorly responding glioblastomas.