From OncoLog, July/August 2005, Vol. 50, No. 7/8

New Techniques in Tumor Ablation

by Sunni N. Hosemann

The idea is an appealing one: What if there were a reliable, nonsurgical way to eradicate cancerous tumors with the precision and immediacy of surgery? What if it were possible, say, to direct a highly targeted heat source at tumor cells from outside the body, causing those cells to vaporize or die? Or to insert a small probe directly into a tumor and destroy the cancer cells by freezing them?

In fact, such minimally invasive ablative techniques do exist; dermatologists use them to remove benign surface lesions, and thanks to refinements in ablative methods and advancements in imaging, ablation has found many uses below the surface as well.

Under imaging guidance, abnormal tissues can be eradicated without surgery. For example, ablative procedures may be done percutaneously or laparoscopically. Extracorporeal lithotripsy requires no entry at all but sends sonographic shock waves from outside the body to destroy abnormal tissues. It is hard to imagine a medical specialty that would not have an interest in some form of nonsurgical ablative technology: cardiologists thread probes into the heart intravenously to eradicate abnormal cardiac cells that can cause cardiac arrhythmias, and gynecologists use ablation to destroy uterine fibroids, sparing some women from undergoing hysterectomies.

In oncology, radiofrequency ablation has become a standard way to treat metastatic tumors in the liver that result from the progression of colorectal and other cancers. Ablation is used as a palliative measure to treat metastatic lesions or some unresectable tumors; inoperable tumors of the liver and lung are among the candidates of interest. But beyond that, most nonsurgical ablative procedures are still investigational in oncology.

John Hazle, Ph.D., a professor and chair of the Department of Imaging Physics, points out some of the distinct advantages of ablation in the treatment of metastatic lesions: “Because the treated area has no ‘thermal memory,’ ablation can be repeated in the same area, unlike radiation therapy. Also, the results of ablation on metastases are immediate, whereas chemotherapy and radiation take more time to shrink symptom-causing tumors.”

Despite the valuable role of ablation in palliation, ablation’s usefulness in primary cancer treatment has been limited to date. This is due in large part to the burden of proof required when a cancer is potentially curable with existing therapies. When a breast tumor is surgically removed, a pathologist confirms that all the cancer, plus a margin of healthy tissue, has been removed. With ablation, the tumor is destroyed but left in place—making it hard to verify that all the malignant tissue has been treated.

“A breast cancer, which could potentially be cured by surgery, represents a very different set of considerations than a benign tumor or one that is considered inoperable or incurable,” said Eric Strom, M.D., an associate professor in the Department of Radiation Oncology and medical director of M. D. Anderson’s Nellie B. Connally Breast Center.

“Nonetheless, we still want to find better ways to do things,” said Kelly Hunt, M.D., a professor in the Department of Surgical Oncology. She believes that surgery—at least for some cancers—could eventually be replaced by more refined, less invasive techniques.

In fact, in a recent pilot study of radiofrequency ablation in breast cancer, researchers at M. D. Anderson showed ablation to be effective for treating small, confined tumors.

“Using ultrasound as a guide, we inserted a small needle-electrode into the center of a tumor and then used radiofrequency ablation to heat the tumor to about 200°F, basically coagulating it,” said Bruno Fornage, M.D., the study’s principal investigator and a professor in the Departments of Diagnostic Radiology and Surgical Oncology. The ablation was followed by standard surgical excision (either mastectomy or lumpectomy) and pathologic examination to confirm whether the cancer cells had indeed been ablated. They had.

“But if the method became standard practice, that postablation excision would not take place,” said Dr. Fornage. “And that raises the question of how we will verify that the cancer is successfully treated in a clinical setting.” Today, pathologic confirmation would require core needle biopsies after the procedure, and these would have to be extensive in order to sample an adequate area. This type of invasive procedure, which is not currently required after surgery, would also provide less definitive results than those obtained by examination of fully excised tissue.

“This study raised very interesting questions about how we evaluate cancer treatment,” observed Nour Sneige, M.D., a professor in the Department of Pathology, who led the pathology arm of the study. “Furthermore, it is not known what pathologic examination would show over time.”

Because of this, and the possibility of malignant-appearing calcifications left behind after ablation, patients treated by this method may require magnetic resonance imaging (MRI) or positron emission tomography scans instead of conventional mammography.

According to Dr. Strom, “The surveillance required by a treatment is a huge consideration. If it is more intense—perhaps more frequent, more specialized—or if it isn’t practical or easy for the patient, then we haven’t gained anything, either medically or practically.”

Another drawback was that the success rates achieved at M. D. Anderson were not reproduced in other centers, which means that the procedure may depend too much on highly specialized skills, particularly in interventional sonography, or require additional training for clinicians.

So what’s the future for tumor ablation in breast cancer treatment?

“At this point, we can’t offer ablation as a treatment for breast tumors because we can’t definitively say it is better than surgery,” said Dr. Fornage. With a philosophical smile, he added, “This study was more interesting for the questions it raised than the ones it answered.”

Dr. Strom agrees but feels that the study also highlights a need for a new level of technology that can more precisely detect tumor cells, a capability that would affect cancer diagnosis and treatment in profound ways.

Forthcoming studies, then, will focus on addressing the questions raised. For instance, later this year, M. D. Anderson will participate in a multicenter, phase II trial of ultrasound-guided cryoablation of breast tumors sponsored by the U.S. National Cancer Institute. Cryoablation, which has been used successfully to treat benign fibroadenomas of the breast and is approved by the U.S. Food and Drug Administration, has potential advantages over radiofrequency ablation for breast tumors. One advantage is that during the procedure, a cryolesion (ice ball) forms that is visible with sonography in real time, giving the operating surgeon and radiologist good visualization and control of the area to be ablated.

Another potential benefit is that cryoablation is not painful because it performs its own local anesthesia (freezing) and can therefore be done in an outpatient setting without a general anesthetic.

“This has been a very beneficial development for treating breast fibroadenomas,” said Dr. Hunt, “and because those are tumors that tend to reoccur in young women, the ablative procedure saves them from multiple surgeries.”

Women with small stage I invasive breast cancers and no preoperative chemotherapy are candidates for the phase II trial. Surgical removal by mastectomy or lumpectomy and pathologic analysis will follow the ablation. Both MRI and ultrasound imaging will be used before and after the procedure. MRIs will be compared with pathology findings, with a match confirming tumor and margin removal.

“If the MRI findings correlate with the pathologist’s findings, we can feel more comfortable in the future using imaging as a basis for determining that a cancer has been removed,” said Dr. Hunt. She believes that this will be a step toward more targeted surgery.

Dr. Hunt is excited about what might be learned from this trial. One of the more intriguing of these will be the immune response to cryoablation. “We know there is a local immune reaction, but some studies indicate that a systemic immune response may take place as well,” said Dr. Hunt. “We need to clearly define that to see what role it might play in cancer treatment.”

For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789.

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