MD op-ed: Overcoming roadblocks for imaging biomarker utilization in clinical cancer trials

With the dramatic increase in capabilities and importance of individualized cancer therapies targeting specific tumors according to molecular makeup, it would seem like a no-brainer to incorporate a wide-range of imaging biomarkers into clinical trials and, eventually, clinical practice.

But that’s not happening, according to Michael Farwell, MD, and his colleagues at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia. In an editorial titled “How Imaging Biomarkers Can Inform Clinical Trials and Clinical Practice in the Era of Targeted Cancer Therapy,” published online April 23 in JAMA Oncology, Farwell and his co-authors outline their take on the three major impediments to the widespread implementation and utilization of new imaging agents in clinical trials. “One would expect to find a plethora of new imaging agents in use,” wrote Farwell et al. “Unfortunately, this is not the case, which raises the following question: Why have we not been able to move beyond standard practice, that is, 18F-fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET-CT), in the application of molecular imaging to clinical trials and clinical practice?”

• Lack of infrastructure - The first obstacle, according to Farwell and his colleagues, is a general absence of infrastructure necessary to move past promising single-center study results into research that incorporates a greater sample size of imaging facilities. “Individual institutions are capable of running pilot studies, but definitive clinical trials require the involvement of multiple institutions, creating challenges due to complexities of radiotracer supply and regulations.” Funding from the National Cancer Institute (NCI) is increasing the feasibility of these multi-center studies in the U.S., while NCI support for specialized imaging trial organizations, including the American College of Radiology Imaging Network’s Experimental Imaging Science Committee, also aids in the development of infrastructure necessary for molecular imaging clinical trials.
• Misunderstanding costs - Farwell and his colleagues believe another challenge facing the trial and eventual clinical implementation of new imaging biomarkers is the misplaced fear of additional costs related to imaging. While superficial costs may be added to clinical trials initially, the doctors say its incorporation will serve to reduce excessive spending over time. “[Imaging studies] can save considerable money in the long run by (1) selecting patients likely to benefit from the drug and (2) providing a unique measure of the pharmacodynamic properties of the drug in the tumor microenvironment,” wrote Farwell et al. “These factors make it possible for imaging biomarkers to increase the probability for success in a clinical trial and to evaluate efficacy more rapidly, thereby helping to avoid investment in ineffective therapies, and promote therapies that might otherwise have been declared a failure.”
• Tradition and time - Doctors and researchers will need to adapt to and accept new imaging agents within the current clinical trial repertoire, Farwell and his colleagues argue. And that, like any other unfamiliar aspect of change, will take time. “Imaging is often perceived as being qualitative and not particularly precise, subject to interpretation, and not as reliable as biopsy,” the authors wrote. “Breaking tradition typically takes time; this process can be expedited with an increased emphasis on rigorous quantitative methods for biomarker imaging, and method standardization across centers.” Accordingly, further testing and research may help convince doctors of the benefit molecular imaging can provide as a “robust and reliable measure” for clinical decision-making.

Farwell and his colleagues believe in the eventual utilization of imaging biomarkers in clinical trials and practice, and the advancement of molecularly specific tumor treatments is speeding the process of implementation—but it will take a concerted effort from all parties involved to eventually reap the benefits. “The integration of imaging biomarkers into clinical trials and clinical practice will require a concerted effort by all involved parties, including oncologists, radiologists, the pharmaceutical industry, imaging companies, and government,” wrote Farwell et al. “In the era of limited government funding, both the pharmaceutical industry and the imaging industry will need to contribute to the support of imaging biomarkers in cancer trials, realizing that in the long run their investments will pay dividends in overall cost savings and in new drugs and new imaging approaches brought to market.”