New randomized controlled clinical trial data have found that post-vascular phase contrast-enhanced ultrasonography is superior to B-mode ultrasonography for detecting smaller hepatocellular carcinomas (HCCs) for patients with liver cirrhosis, according to a plenary paper presented at the International Liver Cancer Association Annual Conference. In addition, the contrast-enhanced ultrasonography method was able to confirm the presence of tumor cells, which eliminates the need for the more expensive follow-up CT and MRI testing currently used to confirm B-mode ultrasound findings.
"Using conventional B-mode ultrasound, it is very difficult to pick up small lesions because of background coarse liver parenchyma due to cirrhosis," the study's lead author, Masatoshi Kudo, MD, PhD, Professor and Chairman at the Department of Gastroenterology and Hepatology of Kinki University School of Medicine and President of Kinki University Medical School, said via email. "On the other hand, using a contrast agent makes it very easy to find very small defects in the Kupffer cells-the examiner only needs to pick up the black lesions in the background white liver."
The trial randomized 622 patients with liver cirrhosis associated with hepatitis B virus or hepatitis C virus to receive B-mode ultrasound or contrast-enhanced ultrasound. Patients in the latter group had contrast-enhanced ultrasound performed 30 to 40 minutes after intravenously receiving Sonazoid, a contrast agent that enables dual-phase imaging during both the vascular and post-vascular phases. For both groups, ultrasound was performed every three to four months.
The efficacy of Sonazoid had been established in a pilot study that was previously published by Kudo and his colleagues in The American Journal of Gastroenterology (2011:106;368-370).
Over the 46-month follow-up (median 974 days), HCC was found in 95 patients, with the tumor size at first detection being 16.7 millimeters for the patients screened with B-mode ultrasound and 13 millimeters for patients screened with contrast-enhanced ultrasound. The median period of initial detection of HCC was 297.5 days for the group screened with B-mode ultrasound and 346.5 days for the contrast-enhanced ultrasound group-not a significant difference, Kudo noted.
The presence of HCC was confirmed for 65.4 percent of the patients whose tumors had been detected with B-mode ultrasound versus 100 percent of the patients screened with contrast-enhanced ultrasound.
Barriers to Implementation
Kudo called the study findings conclusive and noted that they are well-accepted in Japan already. "The problem is that the contrast agent Sonazoid is approved only in Japan, Korea, Taiwan, China, and Norway-but not in all European countries or in the U.S," he said.
Asked to comment for this article, Donald N. Di Salvo, MD, Director for Ultrasound Imaging at Dana-Farber Cancer Center and Associate Professor of Radiology at Harvard Medical School, said that currently there is no consensus for which screening method should be considered standard of care: "If you look at the international hepatology societies, they are all over the map."
Di Salvo spent six months practicing in Italy where contrast-enhanced ultrasound is approved and widely used-and said he considers the screening method to be far superior to B-mode ultrasound. But in the U.S., he noted, it is currently thought of as a "secondary modality" because there is widespread availability of other modalities for screening, including B-mode ultrasound and CT and MRI screening. He was also involved in industry trials in the U.S. that have supported the method's efficacy. But, he said: "We're still waiting for FDA approval."
One challenge for wider adoption of contrast-enhanced ultrasound is that the screening requires the physician be in the room with the patient while the test is being done to read the results, rather than the situation for B-mode ultrasound or other CT or MRI testing-for which technologists perform the test and send the physician the results to read, Di Salvo explained-"I think that's part of the reason it's been delayed." But, the test takes only five to 10 minutes, he added. "So that's a minor potential drawback. I'm convinced by the studies I've seen that have come out of the countries that use it that it is definitely a very valuable tool, and I think it will ultimately become approved."