Contrast-enhanced ultrasound (CEUS) imaging can help determine whether certain drugs are effective at treating cancer in children, according to a new St. Jude Children’s Research Hospital study. CEUS also appears to be more accurate than CT and MR, which are the current standards of care, for predicting treatment response.

Anti-angiogenic drugs can be used to try to cut off the blood supply to the tumors. CEUS can then be used to quantify blood flow and determine if the tumors are responding to the treatment.

“Ultrasound contrast agents are made up of ‘microbubbles’ that are about the same size as red blood cells and are highly visible on ultrasound images,” Dr. Beth McCarville of St. Jude Children’s Research Hospital told HCB News. “We can use these ‘microbubbles' as an indirect method of measuring tumor blood flow.”

The usual method of assessing tumor response to therapy is to measure the size of the tumor because when conventional chemotherapy is working, the tumors shrink. CT and MR are used to measure the tumor’s size.

“Tumor size is not a reliable method to know if chemotherapy that targets blood vessels is working, because these targeted chemotherapies can be very effective without causing tumors to shrink,” said McCarville.

The study included 13 children with metastatic tumors who didn’t respond to earlier therapy and were considered incurable. The researchers had them undergo CEUS to evaluate their response to experimental anti-angiogenic cancer therapy.

The researchers found that CEUS was able to predict which patients would respond to therapy at very early time points. The children who responded to the drugs had longer periods of time before tumors started to get larger and spread compared to the children who didn’t respond to the drugs.

However, larger clinical studies will need to be conducted to prove that CEUS is reliable and reproducible for measuring tumor blood flow and that could take five more years, said McCarville. “Then I think it will become a routine part of monitoring patients who receive therapy that targets blood vessels,” she added.

But if CEUS does become the standard of care for measuring tumor blood flow, children will not be exposed to the ionizing radiation that CT emits or have to undergo sedation for an MR exam.

CEUS is not the only technology under investigation for assessing the effect cancer drugs have on tumors. Two separate research teams were funded in part by the National Institutes of Health’s National Cancer Institute to develop devices that test how tumors respond to a variety of drugs.

The Massachusetts Institute of Technology developed a small device that can be implanted in patients through a standard needle biopsy. The device has reservoirs that release small doses of up to 16 different drugs into certain regions.

A second biopsy needle can be used after 24 hours to retrieve the device and a small column of tissue around it, which can be used to evaluate the effects of the drug on the tumor.

The Fred Hutchinson Cancer Research Center created a device called CIVO, which comprises an array of up to eight needles that can inject small amounts of drugs directly into the tumors. As the drugs are delivered, the needle is retracted, which leaves column-like tracks through the tumor.

After 24 to 72 hours, tumor samples are retrieved and processed and the tumor’s response to each of the drugs is evaluated with an image analysis system.

Both of the devices were used on mouse models and have shown promising results. They are planning on testing the devices in clinical trials in the near future.

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