MR-guided laser therapy proves worth in liver

We have conducted a large-scale 14-year study that found laser ablation with MR guidance is very effective in the treatment of primary and metastatic liver tumors. We presented data from 1394 patients with 3725 lesions at the 2007 European Congress of Radiology. We have since ablated a total of 5041 lesions in 1954 patients. The two largest patient groups suffered from colorectal liver metastases and breast cancer liver metastases.

MR-guided laser-induced thermotherapy (LITT) is a minimally invasive procedure to ablate tumors using optical fibers to deliver high-energy laser radiation to the target lesion. Due to the light absorption, temperatures of up to 120ºC are reached within the tumor, leading to a substantial thermocoagulation (Figure 1). MR imaging is used to 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.

The whole procedure, typically done under local anesthesia on an outpatient basis, takes between 60 and 90 minutes, from positioning the patient to 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. Although MRI is the best modality for guiding the procedure, ultrasound also will work under certain conditions.

LITT offers several advantages over surgery and other types of ablation:

• Treatment can be done on an outpatient basis under local anesthesia. No hospitalization is necessary.
• The treatment can be repeated easily if follow-up studies show new metastases.
• If metastases occur in both liver lobes, all lesions can be ablated.
• Mortality and morbidity rates are both low.
• Multiple laser applications can be used in completely different parts of the liver simultaneously because the different laser applicators do not interact with one another. Therefore, two or three metastases can be ablated simultaneously using anesthesia on an outpatient basis.

Up to 70% of patients with colorectal cancer, which, in many countries, is among the most common cancers, eventually develop liver metastases. These metastases are confined to the liver at the time of diagnosis in 30% to 40% of these patients.

Until recently, the traditional treatment for primary or metastatic liver tumors was surgical resection. Only 25% of patients with liver metastases are candidates for surgery, however, because of the size, distribution, or accessibility of their tumors. The morbidity rate for surgery is high, and therapeutic alternatives are also needed because the incidence of new liver metastases following successful resection of metastases is high: between 60% and 80%.

GROWTH FACTORS

Studies have shown that large liver resections stimulate many growth factors, including those associated with micrometastases that may be located elsewhere in the liver. This is probably the reason why many patients develop new metastases in the first year after surgical resection. Stimulation of these growth factors after surgical resection may also encourage the development of new metastases outside the liver, for example, in the lung or lymph nodes.

We performed MR-guided LITT in 915 patients (mean age 61.6 years) with 2720 liver metastases of colorectal cancer between 1993 and 2006. Survival rates were calculated using the Kaplan-Meier method. A total of 31.1% of the patients had recurrent metastases after surgery, 37.8% had metastases in both liver lobes, 14.8% refused surgical resection, 3.5% had contraindications for surgery, and 12.8% had metastases at difficult localization for surgery. While 703 patients were treated with curative intention, 212 were given palliative treatment.

The mean survival rate for all patients treated with curative intention--starting at the date of diagnosis of the metastases that were treated with LITT-was 3.5 years (95% confidence interval: 3.3 to 3.7 years). The one-year survival rate was 95%; two-year, 73%; three-year, 46%; and five-year, 16%. In the palliative group, mean survival was 2.5 years (95% CI: 2.2 to 2.7 years), with a one-year survival rate of 85%; two-year, 55%; three-year, 22%; and five-year, 6%. Patients who refused surgical resection of resectable liver metastases (n = 135) had a mean survival of 4.1 years (95% CI: 3.5 to 4.7 years).

Prognostic factors are primary lymph node status, number of initial metastases, synchronous versus metachronous metastases, complete ablation of all visible metastases, indication for LITT, and time between primary metastases and development of the first liver metastases.

LIVER INVOLVEMENT

LITT also is an effective treatment option in patients suffering from breast cancer metastases to the liver.

Our study included 865 metastases in 389 consecutive patients (mean age 55.7 years, range 23 to 82 years) treated between 1993 and 2006. A total of 6.2% of the patients had recurrent metastases after surgery, 45.2% had metastases in both liver lobes, 28% refused surgical resection, 1.8% had contraindications for surgery, and 18.8% had metastases at difficult localization for surgery.

The influence of prognostic factors, such as number of treated metastases, presence of bone metastases, and hormone receptor status, was evaluated. We treated 292 patients with curative intention and 97 patients palliatively.

The curative patients had five or fewer metastases and no extrahepatic disease except controlled bone metastases, while the palliative patients had more than five metastases and/or extrahepatic disease. Survival rates were calculated using the Kaplan-Meier method.

The mean overall survival rate was 4.3 years after diagnosis of treated metastases (95% CI: 4 to 4.7 years), with a one-year survival rate of 95%; two-year, 76%; three-year, 56%; and five-year, 34%.

In the curative patient group, the mean survival rate was 4.7 years (95% CI: 4.3 to 5.1 years), significantly superior to the palliative group with a mean survival of 3.1 years (95% CI: 2.6 to 3.6 years) (Figure 2). Patients with at least one positive hormone receptor status (n = 202) had superior survival rates (mean 4.7 years) compared with the patients with negative hormone receptor status (n = 43, mean survival rate 3.7 years). For primary liver tumors (hepatocellular carcinoma), we treated 140 lesions in 90 patients. The mean survival was 4.3 years (95% CI: 3.6 to five years), with a one-year survival rate of 96%; two-year, 74%; three-year, 57%; and five-year, 37%.

LITT can be used in a variety of different liver tumors as well as in extrahepatic tumors such as lymph node or adrenal metastases. The indication for treatment in these patients is based on an individual decision.

COMPLICATIONS, SIDE EFFECTS

Side effects to LITT ablation include pleural effusion, small subcapsular hematoma, fever for a few days, and pain if the lesions had a close relationship to the capsule. Mostside effects are minor, however, and they do not require hospitalization.

The most common side effect we encountered was reactive pleural effusion (9.2%), and puncture was necessary in 1% of cases. A small subcapsular hematoma was found in 4.3% of cases, though no treatment was necessary.

Other side effects were intrahepatic abscess (1.1%), intrahepatic bleeding (0.6%, treatment necessary in 0.1%), intrabdominal bleeding (0.2%, treatment necessary in 0.1%), pleura empyema (0.1%), local infection (0.1%), and injury to bile duct (0.1%).

Four patients (0.2% on patient basis, 0.1% on treatment session basis) died within 30 days. Interestingly, patients who were treated for pancreatic metastases have a higher risk of developing a liver abscess, which was observed in 12.5% of these patients compared with 0.6% in the other patients.

We have found LITT to be an excellent treatment option for management of liver metastases of colorectal carcinoma. We have also found it to be a safe and effective treatment option for selected patients with breast cancer liver metastases. As an effective curative therapeutic procedure, LITT has high local tumor control and survival rates in patients with intrahepatic oligonodular involvement of hepatocellular carcinoma.

DRS. MACK, EICHLER, AND ZANGOS, along with PROF. VOGL, are all from the department of diagnostic and interventional radiology at University Hospital Frankfurt, Johann Wolfgang Goethe-University in Germany.