Imaging Weighs the Evidence

Studies Build the Case for CCTA, FFDM & PET/CT

Health imaging is one area of healthcare that has seen an unprecedented surge in utilization in the past decade. It is perhaps the fastest rising medical expenditure in the United States with an annual growth rate of 9 percent, nearly one-third more than the annual increase in general medical expenditures (approximately 6 percent). As such, policy-makers and payors are increasingly demanding evidence-based data to justify the utilization of many types of imaging procedures.

Evidence-based medicine—the practice of healthcare interventions guided by or based on supporting scientific evidence—is a topic of great interest among both payors and clinicians. The combined pressures of rising medical costs, longer life expectancy, and a demographic spike in patients 50 years and older has led to the charge that healthcare policy-planners have embraced evidence-based medicine solely as a method to rein in increasing expenditures. Public health officials counter that evidence-based medicine ensures that patients receive the best resources for their care, without unnecessary and wasteful procedures.

According to Bruce E. Hillner, MD, professor and eminent university scholar in the department of internal medicine at Virginia Commonwealth University in Richmond, Va., evidence-based medicine research in imaging has been hamstrung by its failure to perform prospective data collection and sufficiently randomize patients. He said this may be due to a lack of tradition in the imaging community to follow the paradigm of the therapeutic community that does clinical trials.

A major reason for this may be imaging’s role as the middleman in the clinical continuum of care. Imaging clinicians usually are not a patient’s primary-care provider, and typically they do not deliver therapeutic care to a patient as a result of their findings. As such, they generally do not have access to a complete patient history prior to performing an imaging exam and are rarely apprised of a patient’s outcome after delivering their imaging interpretation.

“The kinds of studies that radiologists and nuclear medicine physicians have been used to doing look at the sensitivity and specificity of diagnostic tests and are very uncommonly linked to outcomes; but it’s hard to look at outcomes when you’re only one tiny piece in the chain,” says Barry A. Siegel, MD, professor of radiology and chief of the division of nuclear medicine at the Mallinckrodt Institute of Radiology at Washington University in St. Louis.

“Randomized, controlled trials are very hard to do in diagnostic imaging,” he adds. “Clinicians are reluctant to have patients participate in those trials and patients are reluctant to participate.”

CCTA controversy

Cardiac CT angiography (CCTA) is an imaging procedure that has recently drawn fire from policy-makers eager to rein in imaging expenditures. Despite more than 14,000 published studies on CCTA available via the U.S. National Library of Medicine’s PubMed web site, the procedure’s critics are demanding more evidence-based research.

Although numerous single-site studies have demonstrated the efficacy of CCTA compared with conventional invasive angiography in terms of both cost and outcome in thousands of patients, to date there has not been a comprehensive, nationwide study of the procedure. In the face of overwhelming scientific data supporting utilization for many indications, CCTA detractors point to this omission as justification for their opposition.

However, financing for large-scale clinical trials that can deliver evidence-based data for imaging exams, such as CCTA, is scarce to non-existent.

R. Edward Coleman, MD, professor of radiology and chief of the division of nuclear medicine at Duke University School of Medicine in Durham, N.C., observes that the same governmental and private-payor organizations that are demanding evidence-based imaging data are often reluctant to bankroll the necessary studies. “The challenges are getting the funding to get the studies performed, actually getting the studies performed, getting government approval, and then getting reimbursement from the third-party payors,” he says.

When funding is forthcoming, evidence-based imaging trials can present compelling data for utilization, and reimbursement for, modalities and procedures. Two imaging technologies—full-field digital mammography (FFDM) and PET—cleared the funding gauntlet for evidence-based studies and demonstrated that their use can positively impact the delivery of patient care.

Full-field evidence

Starting in October 2001, the Digital Mammographic Imaging Screening Trial (DMIST) enrolled 49,528 women who had no signs of breast cancer at 33 sites in the United States and Canada. As you may know, women in the trial were given both digital and film examinations. Examinations were interpreted independently by two different radiologists. Breast cancer status was determined through available breast biopsy information within 15 months of study entry or through follow-up mammography 10 months or later after study entry.

The trial, sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, was conducted by a network of researchers led by the American College of Radiology Imaging Network (ACRIN).

Results from the study showed no difference in detecting breast cancer for the general population of women in the trial. However, those women with dense breasts, who are pre- or perimenopausal (women who had a last menstrual period within 12 months of their mammograms), or who are younger than age 50 may benefit from having a digital rather than a film mammogram.

Results from a similar study with a larger patient cohort suggest that FFDM is a superior mammography screening technology for all eligible patients.

The utilization of FFDM technology provided higher cancer detection rates than conventional screen-film mammography (SFM) in the Irish National Breast Screening Program, the results of which were presented earlier this summer at the 2008 International Workshop on Digital Mammography (IWDM) in Tucson, Ariz.

“The aim of our study was to retrospectively review the performance of FFDM in a population-based screening program and compare it to the gold standard of SFM with respect to recall rate and cancer detection rate,” according to Niamh Hambly, MD, from the department of radiology at Mater Misericordiae University Hospital in Dublin, Ireland, who discussed the results at IWDM.

The study examined 163,031 women who underwent breast cancer screening in Ireland between Jan. 1, 2005, and Sept. 30, 2007. Of this cohort, 26,593 (16.3 percent) had FFDM performed on a Sectra MDM, Hologic Lorad Selenia, or a GE Healthcare Essential digital mammography system. The remaining patients (136,438 or 83.7 percent) had images acquired via a GE 800T or a Siemens Medical Solutions Mammomat 3000 SFM system.

Images from the national screening program were reviewed by six dedicated breast radiologists using standard mammography alternators for the SFM exams and via a Sectra PACS ID55 mammography review workstation for the FFDM studies. Two radiologists independently read each mammogram and assigned a Breast Image and Data Reporting System (BIRADS) category of 1 to 5 for each image. All solid masses, category 3 to 5 microcalcifications and other suspicious lesions, were biopsied, according to Hambly.

“All samples were evaluated by a dedicated breast pathologist and all cases biopsied were discussed at a multidisciplinary meeting within a week,” she notes.

Recall and cancer detection rates were calculated for FFDM and SFM; recall was defined as the percentage of women screened who were recalled for further diagnostic workup, and the cancer detection rate was defined as the number of cancers detected per 1,000 women screened.

The researchers reported 5,458 women were recalled for further diagnostic work, for an overall recall rate of 3.35 percent. For the SFM cohort, the recall rate was 3.23 percent (4,408 of 136,438) and for the FFDM group, the recall rate was 3.95 percent (1,050 of 26,593).

The overall cancer detection rate was 5.6 per 1,000 women screened. Hambly stated that the cancer detection rate was higher in the FFDM cohort, 6.24 per 1,000 women screened, than in the SFM group, 5.48 per 1,000 women screened.

“This study represents one of the first reviews into the widespread use of digital mammography in a population-based breast screening program,” she says. “The results are very favorable showing a cancer detection rate that is higher than for screen-film mammography. The benefit was apparent in both initial and subsequent screening groups.”

PET/CT powers patient care

An effort to address the lack of prospective, randomized studies in nuclear medicine imaging was launched in November 2005, with the creation of the National Oncologic PET Registry (NOPR). NOPR was developed in response to the Centers for Medicare & Medicaid Services (CMS) proposal to expand coverage for positron emission tomography with F18-FDG PET to include cancers and indications not presently eligible for Medicare reimbursement.

The registry is sponsored by the Academy of Molecular Imaging (AMI) and managed by the American College of Radiology (ACR) and ACRIN. In addition, the American Society of Clinical Oncology (ASCO) and SNM also have played key roles in guiding the project’s development.

The NOPR working group is chaired by Hillner, and co-chaired by Siegel, Coleman, and Anthony F. Shields, MD, professor of medicine and oncology at the Karmanos Cancer Institute at Wayne State University in Detroit. The registry collects information from a PET facility, from the physician requesting a PET scan for a Medicare beneficiary, and from the interpreting physician’s PET report for cancers not currently covered for PET imaging by CMS.

Diagnostic findings from FDG-PET imaging changed the intended care of more than one in three cancer patients, according to a study of first-year data from NOPR, published in the Journal of Clinical Oncology (May 2008). The study analyzed data regarding nearly 23,000 patients contributed to the NOPR by more than 1,200 facilities in the United States that provide PET scans.

The research found that FDG-PET utilization is associated with a 36.5 percent change in the decision of whether or how to treat a patient’s cancer, a management change in almost 75 percent of patients, and it revealed that for patients with a pre-PET plan of biopsy, the post-PET plan had a significant impact on care, with these patients avoiding biopsy in about 75 percent of the cases.

The registry is still open and continues to accept patients, according to Shields.

“As of late March this year, we had 75,000 patients enrolled,” he says. “We are currently running about 200 patients a day; I don’t think any of us expected that we would see this amount of participation when we began.”

SNM president Alexander J. McEwan, MD, professor and chair of the department of oncology, faculty of medicine, at the University of Alberta and director of oncologic imaging at Cross Cancer Institute in Edmonton, Canada, believes that the NOPR model holds great promise as a structure for future evidence-based imaging indications.

“The NOPR trial has shown that you can, on a multi-center basis, collect the type of change of management leading to change of outcomes data that we have to build into imaging trials,” McEwan says. “I think as a base skeleton, with a bit more refinement depending on the complexity of procedure, we can use this model as a starting point for future evidence-based imaging trials.”