ACRIN® trial results identify weakness of whole-body MRI for the staging of common pediatric cancers.
Over the last 40 years, survival rates for children with cancer have increased dramatically in the United States. In the mid-1970s, the combined five-year survival rate for all childhood cancers was less than 60 percent.
Today that figure stands at 83 percent.1,2 This progress is largely due to a better understanding of the nature of childhood cancer and the development of disease-specific, multimodality treatments — including surgery, chemotherapy, and radiation. These valuable advances have been furthered and refined through the robust participation of pediatric patients in multi-institutional clinical trials.
Progressively more informative imaging techniques have played a role in improved childhood cancer management by helping oncologists identify patients who need more intensive therapies and those who need less intensive therapies, thereby reducing the toxicities of treatment. However, the exposure of pediatric patients to ionizing radiation from imaging examinations and the associated lifetime risk of cancer is a growing concern within the medical community and a frequent focus of media attention.
A recent ACRIN® study sought to determine if whole-body MRI could provide oncologists with accurate disease-staging information for pediatric patients with common childhood cancers. The study examined whether or not whole-body MRI, which minimizes radiation exposure, was at least as effective as standard-practice imaging. The 188 pediatric participants enrolled in the ACRIN 6660 clinical trial (Whole-Body MRI in the Evaluation of Pediatric Malignancies) from November 2004 to June 2007 underwent whole-body MRI with turbo short-tau inversion-recovery (STIR) imaging — a technique shown in small, single-institution studies to be as sensitive as conventional bone scintigraphy for detecting skeletal metastases. Trial participants also underwent conventional examinations, to include, depending on the type of cancer, combinations of CT; bone, gallium, or metaoidobenzylguanidine scintigraphy; PET with F-18 fluorodeoxyglucose; and conventional MRI.
The trial results, reported in the February issue of Radiology, show that across all the common childhood cancers evaluated, whole-body MRI did not perform as well as conventional imaging. In particular, 8 of the 134 participants included in the analysis had a positive finding with conventional imaging that was negative with whole-body MRI. Six of eight missed lesions were approximately 1 centimeter or less in diameter, and all were located in the lung or liver.
However, two areas in which-whole body MRI performed better than conventional imaging were detecting metastatic disease in participants with solid tumors (versus those with lymphomas) and detecting skeletal lesions. "There were no missed skeletal lesions with whole-body MRI," says the trial's principal investigator, Marilyn J. Siegel, MD, FACR, professor of radiology at Washington University School of Medicine in St. Louis, Mo., "and MRI allowed detection of substantially more regions of disease per patient than did conventional imaging."
Study recruitment began in November 2004 and was completed in June 2007, and Siegel confirms that the imaging examinations evaluated in the study are still relevant in today's practice. However, she points out that the trial did not evaluate advanced MRI sequences such as diffusion-weighted imaging and fast-acquisition parallel imaging. These techniques are being evaluated for efficacy in more recent clinical trials and were not available when the study began.
Alison Friedmann, MD, MSc, a pediatric oncologist at Massachusetts General Hospital in Boston and ACRIN 6660 trial consultant, acknowledges the growing emphasis in pediatric oncology using MRI in place of imaging examinations exposing pediatric patients to ionizing radiation whenever possible. "We know children are more radiosensitive than adults," says Friedmann, "and as survival rates from childhood cancer continue to improve, the concern about the long-term effects of ionizing radiation gains significantly more importance." Friedmann suggests that the study results confirm generally the importance of MRI as a diagnostic tool for pediatric cancers. More specifically, the results indicate that whole-body MRI may be considered an initial examination for patients who present with pain due to probable bone cancer or as a method for following pediatric patients after baseline evaluation with conventional staging examinations.
The trial was carried out at 21 sites in North America and one site in the Netherlands. All imaging examinations were performed within 21 days of each other, before treatment, and within two months of any diagnostic or surgical procedure. The images were reviewed centrally by 10 reader teams, each composed of an experienced pediatric radiologist and an experienced nuclear medicine physician. An independent panel verified the diagnoses. Detection of metastasis with whole-body MRI and conventional imaging was quantified by using the area under the receiver operating characteristic curve. (See study schema.)
"Being able to confirm the hypothesis of a study and to report a significant finding is always exciting, as was seen recently with the National Lung Screening Trial," says Bradley S. Snyder, MS, an ACRIN Biostatistics and Data Management Center statistician who provided study statistical support. "While such practice-changing results tend to get the most attention, it is also important to publish informative studies like ACRIN 6660." As examples of useful ACRIN 6660 results to disseminate to the medical community, Snyder points to the trial's confirmation of where the technology stands as a modality for staging pediatric cancers as well as its identification of areas in which the technology might be improved.
Concurring that further evaluation of whole-body MRI for staging pediatric cancer should not be abandoned, trial investigators suggest that future trials would benefit from a design with a more homogeneous patient population and that incorporates advanced MRI techniques. Looking further ahead, a study that employs PET/MRI technology holds significant potential for evaluating the best staging strategy. "With a single sedation, pediatric patients with lymphoma, for example, could undergo a PET/MRI examination and, if it turns out the separately interpreted MRI component provides equivalent staging information, you could eliminate the PET. At the very least, the CT component would be eliminated," postulates trial co-investigator Barry A. Siegel, MD, FACR, professor of radiology at Washington University School of Medicine and chair of the ACR PET Core Laboratory. Siegel notes, however, "With only six or seven PET/MRI scanners installed in the United States, it will be a while before we can open that trial."
By Nancy Fredericks, MBA
1. A Snapshot of Pediatric Cancers. National Cancer Institute. Available at http://bit.ly/Pediatric-CancerSnapshot. Accessed Jan. 30, 2013.
2. Childhood Cancers. National Cancer Institute. Available at http://bit.ly/NCIChildhoodCancers. Accessed Jan. 30, 2013.
3. Siegel MJ, et al. “Whole-Body MR Imaging for Staging of Malignant Tumors in Pediatric Patients: Results of the American College of Radiology Imaging Network 6660 Trial.” Radiology 2013;266(2):599–609. Available at http://bit.ly/ACRIN6660.