The Ripple Effect
ACR Clinical Research Center trials create waves of change in patient care.
For more than 40 years, the ACR has supported clinical research endeavors crucial to shaping medical imaging and radiation oncology.
What started out as a modest radiation oncology research program initiated in 1968 by Simon Kramer, M.D., at Jefferson Medical College in Philadelphia, has developed into a multifaceted clinical research center with the College's support. Trials by the center's four groups — ACRIN®, RTOG®, QRRO®, and ACR Image Metrix® — have been carried out by investigators at more than 350 facilities worldwide and are supported by a range of services from study design to statistical analysis and reporting. Each group pursues groundbreaking research that translates into improved patient care, as shown by the various trials described below.
Influencing Lung Screening
One of ACRIN's most significant trials to date has been the National Lung Screening Trial (NLST), which published results to wide acclaim in June 2011. It remains the first clinical trial to show that screening persons at high-risk for lung cancer with low-dose CT results in reduced mortality from the disease. Conducted in conjunction with the National Cancer Institute's (NCI) Lung Screening Study, the work of hundreds of investigators and the contributions of 50,000 trial participants culminated in the finding that 20 percent fewer people randomized to the low-dose CT screening arm died from lung cancer as compared with the chest X-ray arm.
The significant NLST results have already influenced guidelines for patient care. For example, the National Comprehensive Cancer Network® (NCCN®), a consortium of the nation's major cancer centers known for publishing evidence-based clinical guidelines, recently issued new recommendations calling for individuals at high risk for lung cancer to undergo regular screening using low-dose CT. These guidelines follow the NLST's definition of high risk: those aged 55-74 with at least a 30 pack-per-year smoking history who have quit smoking less than 15 years prior, or those 50 years of age or older with a 20 pack-per-year history of smoking and who also have other risk factors besides secondhand smoke. Additionally, the American Cancer Society (ACS) has issued an interim guidance that states, "Adults between the ages of 55 and 74 who meet the eligibility criteria of the NLST and are concerned about their risk of lung cancer may consider screening for early lung cancer detection." Given the high percentage of false-positive results for lung cancer, both he NCCN and ACS strongly encourage patients to discuss the risks and benefits of screening with their doctor.
Despite the NCCN's new recommendations, significant work is needed to implement lung cancer screening, according to Denise R. Aberle, M.D., NLST-ACRIN principal investigator, professor of radiology and vice chair of research and professor of radiological sciences at the University of California at Los Angeles. "We need to establish guidelines for what constitutes a screening center and to implement screening as a multidisciplinary effort," she says. "Standardized image quality, radiation-dose monitoring, definitions of screen positivity, diagnostic follow-up procedures, and outcomes collection will be necessary to ensure quality control. Low-dose CT screening will likely require some degree of regulation, as ultimately occurred with mammography for breast cancer screening."
NLST results have prompted research efforts to address issues itemized by Aberle. One such effort is the Detection of Early Lung Cancer Among Military Personnel (DECAMP) consortium, a multidisciplinary, translational research program based at Boston University. DECAMP is designed to develop and validate molecular biomarkers for the early detection of lung cancer among active military personnel and veterans.
ACRIN received a $3.9 million contract from the university to provide the research infrastructure to conduct DECAMP multicenter clinical trials. These trials have two primary research goals: 1) evaluate airway and blood-based molecular biomarkers to distinguish benign versus malignant diseases among smokers with indeterminate pulmonary nodules found on CT lung scans; and 2) develop and test noninvasive molecular markers in the airway and blood to identify smokers at highest risk for developing cancer.
RTOG Publishes Practice-Changing Research
Like ACRIN, RTOG continues to set new standards in radiation oncology through its strong publication record and abstract presentations at scientific meetings. In 2011, group investigators published nearly 30 papers in peer-reviewed journals and reported research results in more than 40 presentations.
One of the most significant trials discussed this past year was featured in a November 2011 presentation to the NCI Board of Scientific Advisors. Meg Mooney, M.D., M.B.A., chief of the NCI Clinical Investigations Branch, highlighted a trial (RTOG 9408) of combined hormone therapy and radiation therapy for early-stage prostate cancer. Results showed that short-term androgen-deprivation therapy (ADT) given to men in combination with radiation therapy significantly increased long-term survival and disease-free survival rates.1
As the largest randomized trial in the group, RTOG 9408 enrolled nearly 2,000 men with low and intermediate risk of prostate cancer progression and followed their health status for more than nine years (1994-2001) at 212 research centers in the United States and Canada (see Table). The addition of short-term ADT to radiation therapy significantly improved the overall survival rate at 10 years from 57 percent to 62 percent and was associated with 4 percent fewer prostate cancer-related deaths compared with radiation therapy-alone (8 percent versus 4 percent, respectively).
The reduction in disease-specific deaths was accounted for mostly by the intermediate-risk study participants in the radiation therapy plus ADT arm (10 percent versus 3 percent, respectively, in the radiation therapy-alone arm at 10 years), while no reduction in deaths was seen among low-risk participants at 10 years. "The trial's findings have tremendous significance for improving both clinical care and the utilization of health-care resources," comments trial co-principal investigator and lead author Christopher U. Jones, M.D., FACR, from Radiological Associates of Sacramento in California. "The trial results provided strong scientific evidence that, among patients with early-stage prostate cancer, adding short-term ADT to radiation therapy benefits only those patients at intermediate risk of cancer progression."
Jones elaborates, "The higher radiation dose and new treatment technology being employed today with demonstrated higher treatment efficacy could potentially provide the same or greater benefit as the addition of short-term ADT." To test Jones' theory, RTOG launched the RTOG 0815 trial in 2009 to examine the role of short-term ADT combined with modern radiotherapy techniques for men with intermediate-risk prostate cancer. Led by radiation oncologist Alvaro A. Martinez, M.D., FACR, formerly Beaumont Health Systems in Royal Oka, Mich., the trial is expected to yield even more promising results for this patient population.
Providing Practice Insight
While RTOG's clinical trials are setting new practice standards, QRRO is seeking to learn whether these standards are being adopted into clinical practice. QRRO research is based on data gathered via a survey incorporating information specified by each of QRRO's five disease site committees: breast, cervix, lung, prostate, and stomach. The most recent survey, which gathered case data for approximately 2,000 patients receiving radiation treatment at 45 institutions from 2005 through 2007, produced a rich database of radiation therapy performance measures and quality indicators.
For the past two years, presentations at the American Society for Radiation Oncology (ASTRO) Annual Meetings have provided insight into the value of QRRO's survey data. At ASTRO 2010, QRRO Cervix Committee Chair Patricia J. Eifel, M.D., FACR, FASTRO, from M.D. Anderson Cancer Center in Houston, presented the overall assessment of clinical performance measures for 239 patients treated with radiation for locally advanced cervical cancer. Eifel reported "a disturbingly high rate of noncompliance with established criteria for high-quality care of patients with cervical cancer and consistently poor treatment documentation and data, suggesting the lack of quality of communication and consistency of care within the multidisciplinary teams." As QRRO Senior Director Jean B. Owen, Ph.D., states, "It's important to make known prevalent gaps in quality care so that remedial strategies can be put in place to improve patient care."
At ASTRO 2011, QRRO Cervix Committee Member Beth A. Erickson-Wittmann, M.D., FACR, from the Medical College of Wisconsin in Milwaukee, reported on the patterns of practice specific to brachytherapy for cervical cancer. The detailed practice data included statistics showing the dramatic shift from low-dose radiation and high-dose radiation (HDR) brachytherapy treatment and a greater use of HDR outside of academic facilities (see Figure). "Overall, brachytherapy utilization appears appropriate and consistent with national standards," concludes Erickson-Wittmann.
Meeting Drug Industry Needs
Like other groups within the clinical research center, Image Metrix, which was launched in 2007, has experienced continuous growth. According to Chief Scientific Officer Bruce J. Hillman, M.D., FACR, an expanding component of the organization's business is its work with pharmaceutical companies to evaluate novel PET radiotracers for use in drug development. These tracers can evaluate a new drug's effect on a variety of disease processes — specifically, cancer. As Hillman explains, "Measuring the anatomic changes of a tumor's response to treatment with traditionally employed response evaluation criteria in solid tumors has significant drawbacks, including measurement variability and the inherent delay in recognizing a drug's effect."
PET imaging with radiotracers under evaluation has shown significant promise for demonstrating early on — before anatomic changes can be observed — a drug's impact on a tumor and the specific mechanisms of the drug's activity. "This is important when evaluating new chemotherapy drugs targeting tumor angiogenesis, hypoxia, and apoptosis to determine if the intended drug action is occurring," Hillman adds. He also emphasizes the benefits to patients that come from working with pharmaceutical companies and identifying a drug's efficacy sooner in the disease process — but everything depends on getting the most promising new drugs quickly into clinical care.
In addition to monitoring the progress of radiology-related pharmaceuticals, Image Metrix also works with medical device companies on clinical trial data collection connected with all stages of FDA approval. Citing the work performed for Spectra AB, manufacturer of mammography and other medical equipment, Hillman notes, "We accrued hundreds of mammography cases and recruited nearly 20 radiologists to participate in an independent, blinded-reader study that compared images obtained on Spectra AB mammography equipment with images from other leading mammography manufacturers."
From influential clinical trials to improving performance quality and drug review, the ACR Clinical Research Center provides data and research results that improve radiology, radiation oncology, and the entire spectrum of health care. Equipped with a dynamic group of researchers and evaluators, the center will continue to make waves that deliver revolutionary changes in care to facilities — and patients — around the globe.
1. Jones CU. “Radiotherapy and Short-Term Androgen Deprivation for Localized Prostate Cancer,” N Engl J Med. 2011;365:107-118.
By Nancy Fredericks, M.B.A.