The Groundbreakers

Advances in science and technology by the American College of Radiology Imaging Network are driving the practice of radiology into the future.the groundbreakers

"If I have seen further, it is by standing on the shoulders of giants.” It’s been nearly 350 years since Isaac Newton penned that thought in a letter about making new discoveries by building on those of previous researchers.

Today, investigators at the American College of Radiology Imaging Network (ACRIN) are living by that mantra.

“In radiology, we’ve been a very fortunate specialty,” says Mitchell D. Schnall, MD, PhD, FACR, chair of ACRIN and the Eugene P. Pendergrass professor of radiology at the University of Pennsylvania. “ACRIN is playing an active role in innovations on the horizon for the imaging research community. We have benefited from the incredible advances that have occurred in medical imaging over the past several decades. Now it’s our time to step up and make the investments that will continue this legacy.”

Established in 1999 after the National Cancer Institute (NCI) awarded a grant to the ACR, ACRIN is a cooperative group that manages multicenter clinical trials to address imaging-related questions for cancer diagnosis and care. With its oncology program part of the ECOG-ACRIN cancer research group, ACRIN has extended its efforts beyond cancer to address important questions in the cardiovascular, neurological, and molecular imaging domains.

“ACRIN is performing studies that never would have happened otherwise,” says Bruce J. Hillman, MD, FACR, founding principal investigator and past chair of ACRIN. “When I calculated what we’d done by 2009, at the end of my term as chair, we had more than 30 trials opened or completed and had distributed over $100 million dollars to participating facilities to carry out research.”

According to ACRIN investigator Barry A. Siegel, MD, FACR, Washington University professor of radiology at the Mallinckrodt Institute of Radiology, “Prior to ACRIN’s existence, multicenter clinical trials in radiology were few and far between. ACRIN provided the vehicle to change that, making it possible to conduct both conventional imaging trials and innovative, advanced medical trials and to prove the effects of imaging on patient outcomes.”

Conducting Practice-Changing Research

Since its inception, ACRIN has developed a dynamic clinical trials infrastructure and numerous protocols with the potential to expand the role of medical imaging and imageguided therapy in the diagnosis and treatment of cancer.

“The network has been instrumental in facilitating groundbreaking clinical research that is making a difference in the lives of cancer patients,” says Hillman. In particular, two studies conducted by ACRIN investigators have had a major impact on radiologists’ practice: the National Lung Screening Trial (NLST) and the Digital Mammographic Imaging Screening Trial (DMIST).

The DMIST, published in the New England Journal of Medicine in 20051, demonstrated that advances in digital technology can improve our ability to detect breast cancers and potentially save lives, particularly in groups of women for which standard mammography has traditionally been less effective. The NLST was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer. Published in the New England Journal of Medicine in 20112, the findings provided empirical evidence of the benefits of screening patients at high-risk of developing lung cancer with annual low-dose CT scans.

Studies such as these resulted in patients having expanded access to advanced screening thanks to reimbursement for emerging technologies. In 2015, CMS implemented broad national coverage for low-dose CT screening of patients at high-risk of developing lung cancer. “In the past, lung cancer screening was typically paid out of pocket by patients,” remarks Hillman. “There would be little or no CT lung cancer screening if it were not for that trial. Similarly with digital mammography, there was real resistance to paying for digital mammographic screening. Without research, we wouldn’t have these technologies that are extending the lives of patients and providing new opportunities for our specialty.”

Going Beyond Cancer

While ACRIN was launched with funding by NCI, cancer research is not its only focus. The ACRIN Cardiovascular Imaging Committee — chaired by Pamela K. Woodard, MD, FACR, professor of radiology and biomedical engineering at Washington University and vice chair at Mallinckrodt Institute of Radiology — has engaged in five clinical trials. Woodard is principal investigator for one of the studies: Randomized Evaluation of Patients With Stable Angina Comparing Utilization of Diagnostic Examinations (RESCUE). Initially funded by the Agency for Healthcare Research and Quality (AHRQ), RESCUE is evaluating whether coronary artery disease can be diagnosed non-invasively with coronary CT angiography to guide optimal medical therapy for patients with stable angina symptoms. Learn more at bit.ly/ACRIN-RESCUE.

“In the U.S., nearly 10 million people have stable angina,” Woodard says. “Imaging plays a prominent role in diagnosing coronary artery disease in this population and represents a significant national health care expense. RESCUE is an elegantly designed trial, where we’re looking at how imaging might impact treatment strategy. We expect results from this study to guide best treatment options in emergency rooms around the country for the millions of patients with stable angina.”

Funding from AHRQ allowed 1,050 participants to be enrolled at 44 institutions internationally. Additional funding from the ACR Foundation’s ACRIN Fund allowed the RESCUE team (principal investigator Arthur E. Stillman, MD, PhD, FACR, Emory University) to conduct at least 12 months of follow-up on all participants to collect data on health care utilization, cardiac events, and quality of life. “With help from the ACR Foundation, we were able to analyze trends and can now publish data from the trial,” she says.

Providing Evidence to Guide Practice

Now more than ever, evidence-based medicine is being used to decide which tests and therapies to use, says David A. Mankoff, MD, PhD, Gerd Muehllehner professor of radiology and vice chair for research in the department of radiology at the Perelman School of Medicine at the University Pennsylvania. “It’s also being used to rationalize and contain costs. Unfortunately, imaging is often perceived as one of the big cost drivers. Evidence generated by multicenter imaging trials has the power to demonstrate exactly what works across the patient population. ACRIN has always been the best organization to do that.”

Mankoff, who chairs the ECOG-ACRIN Experimental Imaging Sciences Committee, explains that many of ACRIN’s smaller trials provide proof of concept that inspires other organizations to invest in a broader trial. “There are some protocols that achieve early success in single centers but don’t provide multicenter evidence to support further investigation. That’s where ACRIN comes in.”

Schnall agrees: “We live in an era of data and analytics. As a specialty, we must be prepared to step up to the table with strong evidence of efficacy. If we’re not building evidence ourselves, someone else will decide for us what we should or should not do. ACRIN gives us the opportunity to initiate programs rapidly, generate pilot data as evidence in grant applications, and get resources for larger, more impactful studies. That creates a multiplier effect.”

Translating Imaging Advances Into Clinical Practice

In the new era of precision medicine, the importance of clinical imaging trials will only increase in importance. “Precision medicine is advancing quickly, and imaging is on the front lines of the process,” says Mankoff. “The field of medicine demands rigorous validation for everything that gets translated to the clinic. Imaging is coming under the same level of scrutiny as other aspects of patient care to make sure that it’s evidence based.”

Toward that end, ACRIN is developing more precise quantitative approaches to diagnosis and image-guided therapy, including surveillance of high-risk populations, administration of targeted therapies, and use of biomarkers to evaluate therapeutic response.

“ACRIN has hit some home runs that have had a major impact on health care,” says Siegel. “While other trials may not be as significant, they have allowed us to create a culture of multicenter trials that is embedded in the radiology community. We’ve also developed a generation of investigators who know how to perform multicenter trials. That’s an important contribution to the specialty.”

Training Tomorrow’s Researchers

An equally vital role for ACRIN is to help prepare the next generation of imaging investigators. “For young investigators, it is absolutely essential to have a place to conduct research,” Mankoff emphasizes. “They need to be confident that there is a home for them. Supporting and inspiring new investigators is one of the most critical things the ACR Foundation can do for our specialty.”

Siegel adds that having a predictable source of funding for research will encourage new researchers to enter the field. “As radiologists, we owe it to our specialty to inspire the next generation of researchers. Without ongoing funding, some of what we have accomplished over the last 15 years could be lost. There are still so many questions that need to be answered about how to use imaging wisely and efficiently in practice, and there’s no real vehicle for doing that without ACRIN.”


By Linda Sowers, freelance writer for ACR Press

 

ENDNOTES
1. Pisano ED, et al. Diagnostic performance of digital versus film mammography for breast-cancer screening. New England Journal of Medicine 2005;353:1773–1783. Available at bit.ly/
NEJM-ACRIN.
2. The National Lung Screening Trial Research Team. Reduced lung-cancer mortality with lowdose computed tomographic screening. New England Journal of Medicine 2011;365:395–409.
Available at bit.ly/NEJM-NLST.

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