Home

Cover Story

Table of Contents

E-Newsletter

Article Archive

Editorial Calendar

Datebook

Writers' Guidelines

Orgs/Links

Opinion Polls

Reprints

Forum

For other articles and previous issues click here.

January 16, 2006

Hatching a New Gold Standard? Will MR-Guided Laser Therapy Replace Traditional Surgery for Liver Metastases?
By Beth W. Orenstein
Radiology Today
Vol. 7 No. 1 P. 22

Up to 70% of patients with colorectal cancer—which is among the most common cancers in the United States—eventually develop liver metastases.

In 30% to 40% of those patients with metastases, their metastases are confined to the liver when diagnosed.

The traditional treatment for primary or metastatic liver tumors is surgical resection. However, only 25% of those with liver metastases are candidates for surgery because of the size, distribution, or accessibility of their tumors. Also, the morbidity rate for surgery is high.

A team of German investigators believes it has found a therapeutic technique using MR-guided laser ablation that is as effective as surgical resection for the treatment of metastatic liver tumors—and in many cases may be even more promising. The researchers reported on a large-scale, 12-year study of their technique at RSNA in Chicago at the end of this past November.

Martin Mack, MD, associate professor of diagnostic and interventional radiology at the University of Frankfurt in Frankfurt, Germany, and lead author of the study, believes laser ablation with MR guidance will have wide-ranging impact on the treatment of lesions throughout the body and, eventually, could replace traditional surgery as the gold standard of treatment. Coauthors of the study are Katrin Eichler, MD; Thomas Lehnert, MD; Dirk Proschek, MD; Joern O. Balzer, MD; and Thomas J. Vogl, MD.

“Laser is as effective as surgery but with far less morbidity and mortality,” Mack says.

Reduced Morbidity & Mortality
Researchers have been looking for therapeutic alternatives because the incidence of new liver metastases following successful resection of metastases is between 60% and 80%. Many studies have shown that large liver resections stimulate many growth factors, including growths of micro-metastases, which are potentially somewhere else in the liver. “This is probably the reason why many patients are developing new metastases already in the first year after surgical resection,” Mack explains. He adds there are also indicators that the stimulation of the growth factors after surgical resection not only stimulates the development of new metastases within the liver, but also outside the liver, such as in the lung or lymph nodes.

Also, surgical resection has a high rate of clinically relevant side effects. “It’s around 30% depending on the literature,” Mack says. Typically, too, patients who undergo resection must stay a couple days in the intensive care unit and a couple weeks afterward on the patient care floors of the hospital.

The mortality rate within 30 days after liver resection is between 3% and 5% following surgery, Mack says. Also, morbidity is increased in 30% of patients due to complications or side effects such as pleural effusion, compromised liver function, or bleeding. Patients who develop serious complications are often hospitalized for prolonged periods.

Mack and his researchers were looking for an alternative that would achieve survival statistics at least similar to those attained with surgery—if not better. “Ideally, such therapeutic alternatives also should be less invasive than liver resection, should have a low complication rate, should be possible under local anesthesia for patients with general contraindications for surgery, and should be less expensive,” Mack says.

The researchers in Frankfurt used laser-induced interstitial thermotherapy (LITT) to ablate the liver tumors. The minimally invasive procedure uses optical fibers to deliver high-energy laser radiation to the target lesion. As a result, tumor temperatures rise to approximately 120° C, leading to a substantial thermocoagulation.

In the procedure, the physician uses MR imaging to guide placement of the laser applicator in the tumor and monitor the progress of thermocoagulation. “The thermosensitivity of certain MR sequences is the key to real-time monitoring, allowing accurate estimation of the actual extent of the thermal damage,” Mack says.

The whole procedure takes between 60 and 90 minutes, including positioning the patient, CT-guided puncture, MR-guided tumor ablation, and finally removal of the laser application systems. The laser ablation itself takes between 10 and 30 minutes.

Ultrasound Alternative
Mack says MRI is the best modality for guiding the procedure, but ultrasound will also work under certain conditions. The main problem with ultrasound is the gas bubbles that develop during the ablation procedure. “This is causing a problem regarding the visualization of the treatment effects behind the bubbles because it is not possible to look through the bubbles with ultrasound,” Mack says. “Some improvements were made by the combination of ultrasound and ultrasound with contrast agents.”

Between 1993 and 2005, Mack and his colleagues performed MR-guided LITT in 839 patients with 2,506 liver metastases of colorectal cancer. The number of metastases treated were: one metastases in 29% of the patients; two metastases in 26.5% of the patients; three metastases in 17.8% of the patients; four metastases in 10.6% of the patients; five metastases in 7.5% of the patients; and more than five metastases in 8.6% of the patients.

One third of the lesions were 2 centimeters or less in diameter (mean applied energy 54.5 Kilojoules [KJ]); 33.3% were between 2 and 3 centimeters (mean applied energy 94.9 KJ); 18.1% were between 3 and 4 centimeters (mean applied energy 133.45 KJ); and 15.6% were larger than 4 centimeters in maximum diameter (mean applied energy 189.1 KJ).

Nearly 78% of the 651 patients (77.6%) had five or fewer liver metastases and no extrahepatic disease at the time of inclusion. Those patients were treated with curative intentions. The 188 patients (22.4%) with more than five metastases and/or limited extrahepatic disease were given the treatment as a palliative treatment.

The mean age of all patients was 61; 67.2% were male and 32.8% were female. The staging distribution was: T1, 2%; T2, 10.1%; T3, 72.6%; and T4, 15.4%.

The interval between diagnosis of the primary tumor and the liver metastases was less than six months in 57.7% of patients studied; 42.3% had metastases occurring or starting at different times.
The researchers found that the overall survival rate of the patients in the long-term study was at least as good as surgical resection. Survival rates were calculated using the Kaplan-Meier method.

“The overall length of survival in this long-term study was 3.8 years after the date of diagnosis, which is comparable to surgery in which the survival rate is 1.5 to five years,” Mack says. Ninety-three percent of patients were alive one year after treatment. After two years, 72% were alive, and after three years, 47% were alive. The five-year survival rate was 24%.

The mean survival in the curative group was four years and in the palliative group was 2.8 years. The mean survival in 119 patients, who were clear candidates for surgery but refused surgical resection of the metastases, was five years.

Side Effects
The researchers found some side effects to LITT ablation, including pleural effusion, small subcapsular hematoma, fever for a few days, and pain, if the lesions had a close relationship to the liver capsule, Mack says. However, he says, most side effects are minor and do not cause hospitalization. Clinical relevant side effects are found in only 1.5% to 2% of cases, and the mortality rate is 0.2%, Mack says.

Mack concludes that LITT has at least four distinct advantages over traditional surgery:

1. Treatment can be done on an outpatient basis under local anesthesia. No hospitalization is necessary.

2. Treatment can be repeated easily, if follow-up studies are showing new metastases. This is an important advantage, Mack says. “If there are recurrent liver metastases after surgical resection in the liver, it is extremely difficult or often not possible to repeat resection for the recurrent lesion where the laser ablation can be repeated multiple times without any problems.”

In its series, the maximum time the researchers repeated the procedure was 13. However, if follow-up examinations show multiple new lesions in the liver or extensive extrahepatic disease, additional LITT sessions are not indicated, Mack notes.

3. If there are metastases in both liver lobes, all lesions can be ablated. This is also an important advantage, Mack says, “because doing both lobes with resection is difficult. Typically with resection, a left or a right lobe is done.”

The problem is that in many cases, a large amount of normal and healthy liver tissue must be resected to reach a lesion whereas LITT can selectively destroy the lesion with a safety margin without destroying unnecessary normal liver tissue, Mack says.

4. Clearly, Mack says, the low mortality and morbidity rates achieved with LITT are a definite advantage.

Size Matters
The technique does have some disadvantages, however, Mack says. One is that the treatment of metastases larger than 5 centimeters in diameter is not possible. Another is that small lymph node metastases in the abdomen can be missed. “This is an extremely rare situation, though,” Mack says.

Also, treatment of patients with more than five metastases is problematic. However, patients with such a high number of metastases often cannot be treated with surgery either, Mack says.

Mack believes laser light also has advantages over radiofrequency ablation, which is also being used increasingly to ablate liver tumors. One advantage is that the laser can be combined with MR. “To generate a MR image, a radiofrequency pulse is used. If there is any radiofrequency source in the MR room, there is always interference between the radiofrequencies from the RF generator and the radiofrequencies from the MR scanner,” Mack says. “The result is that the MR image is completely destroyed. Even with an MR-compatible RF probe, it is necessary to disconnect the probes for every MR scan and this is quite uncomfortable for the patient,” he says.

Another advantage of laser is that multiple laser applications can be used in completely different parts of the liver simultaneously because the different laser applicators do not interact, Mack says. Multiple RF probes would interact. “Therefore, two or three metastases can be ablated simultaneously with the laser under anesthesia on an outpatient basis. With RF, it is only possible to ablate one metastatic tumor after the other. Therefore, treatment time is significantly shorter with laser.”

Remaining Questions
The big questions facing researchers now, Mack says, are: What is the best technique for ablation, for which patients, and at what time point in their oncological management?

Mack notes that laser ablation also works well in liver metastases where the primary cancer is breast, but the researchers have not been able to perform a randomized study so far. “We received a really good grant for such a study and had good cooperation with several departments of surgery for the study,” Mack says, “but almost all patients refused surgical resection and wanted to have LITT after they were informed about the study.

“When the patients were told the risk of LITT was lower and that the results of LITT are very good, they wanted LITT because they knew that if it failed, they could have surgery afterward.”

While Mack believes laser ablation will become the gold standard vs. traditional surgery for liver and other metastases, he says the change won’t come easily. Traditionally, resistance to change is high, especially in surgical departments, he says. Interventional radiologists perform laser treatment that could take patients and business from surgeons and make surgeons reluctant to refer them. Also, many oncologists still prefer systemic chemotherapy instead of ablation.

However, Mack says, “there are many positive synergistic effects if there is good cooperation among the disciplines.”

— Beth W. Orenstein is a freelance health writer based in Northampton, Pa., and a regular contributor to Radiology Today.

Subscribe to Radiology Today Magazine!