CHICAGO—The use of radiofrequency and microwave technology to directly destroy cancer in the liver appears to increase survival profoundly in patients who are capable of undergoing the percutaneous treatment procedures, yet doctors who routinely use radiologic guidance to perform the procedures suggest that it remains underutilized.
“Medical oncologists have not embraced these ablation procedures, and few of them will refer their patients with metastases to interventional radiologists,” said Fred T. Lee, Jr., MD, Professor of Radiology at the University of Wisconsin-Madison, moderator of a symposium on ablation techniques here at the Radiological Society of North America Annual Meeting.
One of the problems, Dr. Lee explained, has to do with the difference in finances of companies that develop devices and those that produce drugs: “The device companies do not have the kind of money required to put together studies of thousands of patients that are available to large pharmaceutical companies. Therefore, the studies on liver metastases ablation and other ablation techniques are smaller and may not have the same impact on practice as the major drug trials do.”
But the trials that are being performed with ablation techniques are showing longer survival times for patients and the ability to attack even tumors in critical anatomic areas.
In one of the several papers discussed in the symposium, researchers said that laser ablation of breast cancer metastases to the liver achieved a median long-term survival of more than five years for women with one or two lesions treated with curative intent.
“Magnetic resonance-guided laser ablation improves the survival of patients with breast cancer liver metastases,” said Martin Mack, MD, Associate Professor of Diagnostic and Interventional Radiology at J.W. Goethe University in Frankfurt, Germany.
He described the outcomes after laser ablation treatment in 421 patients over the period of October 1993 to October 2007. The doctors treating the patients with the system ablated 965 metastases in these patients in 813 sessions.
The doctors proceeded with curative intent in 309 of the patients and palliative intent in 112 patients. Curative attempt was defined as treatment in a patient who had no more than five lesions that were all less than 5 cm in diameter and who had no extrahepatic lesions. The patients treated with palliative intent had more than five lesions or lesions that were larger than 5 cm in diameter or had metastases in the lungs, lymph nodes, or bone. Even in the patients with widespread metastases, however, the liver ablation procedure still showed survival benefits.
“Controlled bone metastases are not an absolute contraindication for the ablation treatment,” Dr. Mack said. “However, the value of magnetic resonance-guided ablation for the palliative patient group needs further evaluation.”
Keys for Success
The key to successful treatment is to make sure that there are wide margins around the tumor, he explained. The study showed that the coagulated tissue is almost double the volume of the tumor, but after 12 months the necrotic tissue is gradually resorbed by the body so that less than half the killed tissue remains.
The results for laser ablation of breast cancer metastases to the liver compare well with chemotherapy, he said, noting that chemotherapy can create severe morbidity. Overall survival rates for patents treated with various chemotherapy regimens range from 11 to 22 months.
Of the study's cohort of 421 patients—both those treated with curative and those treated with palliative intent—the overall survival rates at one, two, three, and five years were 85%, 63%, 45%, and 28%, respectively. “These are really impressive results,” Dr. Mack said.
The mean overall survival duration for patients treated with curative intent was five years compared with 3.2 years for patients treated with palliative intent.
For patients treated with curative intent who had one to two metastases, the mean overall survival was 5.2 years; for patients with three to four metastases, the mean overall survival was 4.6 years, and for patients with five metastases, survival was almost the same —4.5 years.
Dr. Lee commented that while the results described by the German researchers are impressive, comparing the survival rates between those in his study and those performed with chemotherapy may suffer from selection bias. He said a randomized comparative study should, as Dr. Mack suggested, be performed.
Another study presented at the RSNA meeting considered factors that made patients better candidates for treatment. The best chance of long-term survival among patients undergoing percutaneous laser ablation of hepatocellular carcinoma appears to be good liver function at the start of treatment and smaller size of the tumors, said Claudio Pacella, MD, Head of Radiology at Ospedale Regina Apostolorum in Albano Laziale, Italy. In fact, he said, there is a suggestion that in these selected patients outcomes are good enough to recommend ablation as a first-line treatment.
The study's retrospective look over a 12-year history of using neodymium-doped yttrium aluminum garnet (Nd:YAG) laser ablation of lesions in cirrhotic patients identified factors that gave patients the best chance of long-term survival.
“We observed evidence of better survival at five years—56.4 percent of patients in this subgroup— if the patients were in Child's Class A and the hepatocellular cancer nodules were less than two centimeters in diameter,” Dr. Pacella said.
The reviewers scrutinized medical records from nine Italian centers and were able to identify 432 patients—278 men, 154 women—who underwent treatment to ablate 548 tumors; 344 patients presented with one tumor, 60 had two tumors, and 28 had three tumors. Over the course of the study, the hospitals registered a perioperative mortality rate of 0.7%.
About 39 percent of patients had tumors smaller than 2 cm in diameter, 242 patients (44%) had tumors that were 2.1 to 3 cm in diameter, and 91 had tumors that were 3.1 to 4 cm in diameter. Treatment was successful in destroying 79% of the tumors that were smaller than 4 cm.
Dr. Pacella said that while univariate analysis identified several possible variables that would account for an improved chance of long-term survival, multivariate analysis determined that two factors predicted outcome: albumin level and a tumor size no larger than 3 cm in diameter.
“Selection of patients with good liver function and small-sized hepatocellular carcinoma are the main factors affecting patients' outcome after ultrasound-guided percutaneous laser ablation,” Dr. Pacella said. “The evidence of albumin levels as predictive factors of survival of cirrhotic patients with hepatocellular carcinoma stressed the role of liver function as a main determinant of patients' outcome.”
Another group of interventional radiologists reported that even in cases in which liver cancer lesions are perilously close to or abut the diaphragm, radiofrequency ablation is still a viable tool to destroy the malignancy within acceptable safety margins.
The study was a retrospective review of cases at Samsung Medical Center at Sungkyunkwan University School of Medicine in Seoul.
Tae Wook Kang, MD, a radiologist there, identified 667 patients who underwent radiofrequency ablation between 2000 and 2006. Of those, 39 cases were found in which the tumor treated abutted or was within 5 mm of the diaphragm. Those patients were matched with 41 similar individuals whose lesions were not located near the diaphragm.
“If the index tumor abuts the diaphragm, the interventional radiologist must balance two conflicting factors: Complete ablation and safe ablation,” Dr. Kang said. One patient in the abutting group experienced a hemothorax, and there was also one case of pleural effusion. These adverse events were not seen in the non-abutting patients.
Similarly, transient lung injury occurred in seven patients in the abutting group, but there were no such problems in the non-abutting group.
The patients were all approximately 60 years old, and about two thirds of the patients in both groups were men. The tumors ranged in size from about 1.75 to 3 cm in diameter.
The technical success rate in ablating the tumor was 84% in the abutting tumor group of patients compared with 98% in the non-abutting patients. About 29% of the patients in the abutting tumor group had local tumor progression compared with 6% of the patients in the non-abutting group.
“Percutaneous radiofrequency ablation for hepatocellular carcinoma abutting the diaphragm is a safe procedure without major complications,” Dr. Kang concluded. He noted that the study results are limited due to its retrospective analysis and that the researchers did not consider the variability in the experience of the three interventional radiologists involved in the surgeries.
Microwave Ablation May Be Improvement
While the studies illustrate the long-term safety and effectiveness of radiofrequency ablation, there is a suggestion that a new method of percutaneous ablation of liver metastases using microwave energy might surpass radiofrequency.
“Microwave ablation appears to destroy the tumors more rapidly than radiofrequency ablation and act more predictably,” said William Lees, MD, Professor of Radiology at University College London.
The study he reported at the meeting included 38 patients with colorectal metastases to the liver, randomly assigned for treatment with either microwave energy or radiofrequency ablation. Each tumor site was treated for six minutes, with movement of the needle permitted if a larger ablation zone was required. Only tumors smaller than 5 cm were treated in this way.
“We treated 56 tumors with microwave thermal ablation, and we treated 83 tumors with radiofrequency ablation,” Dr. Lees said. There were a mean of 3.7 tumors in each patient, and the lesions had a mean diameter of 3.8 cm.
After six minutes of treatment, the microwave treatment had ablated a zone of 55 mm compared with 39 mm with radiofrequency techniques. After 12 minutes, the microwave ablation extended to 74 mm compared with 48 mm for radiofrequency ablation.
Dr. Lees explained that microwave ablation involves the phenomenon known as “heat sink,” in which the ablation areas appear to be greater in vivo than when experiments are performed ex vivo. He estimated that microwave ablation techniques deliver heat at two to three times the rate of radiofrequency.
However, before microwave is ready for prime time, some technical problems with the equipment need to be sorted out, he said—primarily differences in cooling needles, the needle size, eliminating bulky coaxial cables, and avoiding vascular damage.
“My results are comparable to what Dr. Lees has reported,” said Wisconsin's Dr. Fred Lee. “We think that microwave ablation will eventually overtake radiofrequency techniques because it can deliver heat more predictably to the tumor site.” He agreed that issues with equipment need to be sorted out, and said that groups performing microwave ablation are basically building the devices themselves without a lot of standardization.