Thermal ablation of colorectal liver metastases: a position paper by an international panel of ablation experts, The Interventional Oncology Sans Frontières meeting 2013.

OBJECTIVES: Previous attempts at meta-analysis and systematic review have not provided clear recommendations for the clinical application of thermal ablation in metastatic colorectal cancer. Many authors believe that the probability of gathering randomised controlled trial (RCT) data is low. Our aim is to provide a consensus document making recommendations on the appropriate application of thermal ablation in patients with colorectal liver metastases. METHODS: This consensus paper was discussed by an expert panel at The Interventional Oncology Sans Frontières 2013. A literature review was presented. Tumour characteristics, ablation technique and different clinical applications were considered and the level of consensus was documented. RESULTS: Specific recommendations are made with regard to metastasis size, number, and location and ablation technique. Mean 31 % 5-year survival post-ablation in selected patients has resulted in acceptance of this therapy for those with technically inoperable but limited liver disease and those with limited liver reserve or co-morbidities that render them inoperable. CONCLUSIONS: In the absence of RCT data, it is our aim that this consensus document will facilitate judicious selection of the patients most likely to benefit from thermal ablation and provide a unified interventional oncological perspective for the use of this technology. KEY POINTS: • Best results require due consideration of tumour size, number, volume and location. • Ablation technology, imaging guidance and intra-procedural imaging assessment must be optimised. • Accepted applications include inoperable disease due to tumour distribution or inadequate liver reserve. • Other current indications include concurrent co-morbidity, patient choice and the test-of-time approach. • Future applications may include resectable disease, e.g. for small solitary tumours.

Image-guided tumor ablation: standardization of terminology and reporting criteria--a 10-year update.

Image-guided tumor ablation has become a well-established hallmark of local cancer therapy. The breadth of options available in this growing field increases the need for standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison among treatments that use different technologies, such as chemical (eg, ethanol or acetic acid) ablation, thermal therapies (eg, radiofrequency, laser, microwave, focused ultrasound, and cryoablation) and newer ablative modalities such as irreversible electroporation. This updated consensus document provides a framework that will facilitate the clearest communication among investigators regarding ablative technologies. An appropriate vehicle is proposed for reporting the various aspects of image-guided ablation therapy including classification of therapies, procedure terms, descriptors of imaging guidance, and terminology for imaging and pathologic findings. Methods are addressed for standardizing reporting of technique, follow-up, complications, and clinical results. As noted in the original document from 2003, adherence to the recommendations will improve the precision of communications in this field, leading to more accurate comparison of technologies and results, and ultimately to improved patient outcomes. Online supplemental material is available for this article .

Image-guided tumor ablation: standardization of terminology and reporting criteria--a 10-year update.

Image-guided tumor ablation has become a well-established hallmark of local cancer therapy. The breadth of options available in this growing field increases the need for standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison among treatments that use different technologies, such as chemical (eg, ethanol or acetic acid) ablation, thermal therapies (eg, radiofrequency, laser, microwave, focused ultrasound, and cryoablation) and newer ablative modalities such as irreversible electroporation. This updated consensus document provides a framework that will facilitate the clearest communication among investigators regarding ablative technologies. An appropriate vehicle is proposed for reporting the various aspects of image-guided ablation therapy including classification of therapies, procedure terms, descriptors of imaging guidance, and terminology for imaging and pathologic findings. Methods are addressed for standardizing reporting of technique, follow-up, complications, and clinical results. As noted in the original document from 2003, adherence to the recommendations will improve the precision of communications in this field, leading to more accurate comparison of technologies and results, and ultimately to improved patient outcomes.

Is it time to reconsider the BCLC/AASLD therapeutic flow-chart?

PURPOSE: Recommendations of the Barcelona Clinic Liver Cancer (BCLC) therapeutic flow-chart, endorsed by the American Association for the Study of Liver Diseases (AASLD), are the most applied worldwide. Over recent years, however, several referral centers have questioned some of the BCLC treatment allocations and proposed alternative strategies. The present study plans to review and discuss these suggestions, with the aim to evaluate whether there are well-grounded reasons to reconsider some of the BCLC/AASLD recommendations. METHODS: A search was made into the MEDLINE database, focusing on randomized controlled trials, meta-analysis reviews, case-control studies, concordant clinical trials on novel therapies and studies reporting the opinion of respected experts. Their results and conclusions were compared stage by stage with BCLC/AASLD recommendations. RESULTS: In stage 0 (very early, or single <2 cm, or carcinoma in situ, Child A) radiofrequency should replace resection. In stage A (early, or single or three nodules up to 3 cm, Child A-B) radiofrequency and resection should expand their indications. In stage B (intermediate, or multinodular, Child A-B) resection and transplantation should expand their indications, while intra-arterial therapies are changing from conventional to selective treatments. In stage C (advanced, portal invasion or extrahepatic disease, Child A-B) systemic therapies should offer previously unknown promising options. CONCLUSION: In our opinion, so much evidence leads to suggest it is time to reconsider several BCLC/AASLD recommendations. Some treatments are comparable in results but vary in costs, local availability, or complication rates.

Breast cancer liver metastases: US-guided percutaneous radiofrequency ablation--intermediate and long-term survival rates.

PURPOSE: To retrospectively assess the local control and intermediate- and long-term survival of patients with liver metastases from breast cancer who have undergone percutaneous ultrasonography (US)-guided radiofrequency (RF) ablation. MATERIALS AND METHODS: This study was approved by the hospital ethics committee, and all patients provided written informed consent. RF ablation was used to treat 87 breast cancer liver metastases (mean diameter, 2.5 cm) in 52 female patients (median age, 55 years). Inclusion criteria were as follows: fewer than five tumors, maximum tumor diameter of 5 cm or smaller, and disease either confined to the liver or stable with medical therapy. Forty-five (90%) of 50 patients had previously undergone chemotherapy, hormonal therapy, or both, and had no response or an incomplete response to the treatment. Contrast material-enhanced computed tomography and US were performed to evaluate complications and technical success and to assess for local tumor progression during follow-up. The Kaplan-Meier method was used to assess survival, and results were compared between groups with a log-rank test. Cox regression analysis was used to assess independent prognostic factors that affected survival. RESULTS: Complete tumor necrosis was achieved in 97% of tumors. Two (4%) minor complications occurred. Median time to follow-up from diagnosis of liver metastasis and from RF ablation was 37.2 and 19.1 months, respectively. Local tumor progression occurred in 25% of patients. New intrahepatic metastases developed in 53% of patients. From the time of first RF ablation, overall median survival time and 5-year survival rate were 29.9 months and 27%, respectively. From the time the first liver metastasis was diagnosed, overall median survival time was 42 months, and the 5-year survival rate was 32%. Patients with tumors 2.5 cm in diameter or larger had a worse prognosis (hazard ratio, 2.1) than did patients with tumors smaller than 2.5 cm in diameter. CONCLUSION: Survival rates in selected patients with breast cancer liver metastases treated with RF ablation are comparable to those reported in the literature that were achieved with surgery or laser ablation.

Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: Is resection still the treatment of choice?

UNLABELLED: If liver transplantation is not feasible, partial resection is considered the treatment of choice for hepatocellular carcinoma (HCC) in patients with cirrhosis. However, in some centers the first-line treatment for small, single, operable HCC is now radiofrequency ablation (RFA). In the current study, 218 patients with single HCC

Image-guided tumor ablation: standardization of terminology and reporting criteria.

The field of interventional oncology with use of image-guided tumor ablation requires standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison between treatments that use different technologies, such as chemical (ethanol or acetic acid) ablation, and thermal therapies, such as radiofrequency (RF), laser, microwave, ultrasound, and cryoablation. This document provides a framework that will hopefully facilitate the clearest communication between investigators and will provide the greatest flexibility in comparison between the many new, exciting, and emerging technologies. An appropriate vehicle for reporting the various aspects of image-guided ablation therapy, including classification of therapies and procedure terms, appropriate descriptors of imaging guidance, and terminology to define imaging and pathologic findings, are outlined. Methods for standardizing the reporting of follow-up findings and complications and other important aspects that require attention when reporting clinical results are addressed. It is the group's intention that adherence to the recommendations will facilitate achievement of the group's main objective: improved precision and communication in this field that lead to more accurate comparison of technologies and results and, ultimately, to improved patient outcomes. The intent of this standardization of terminology is to provide an appropriate vehicle for reporting the various aspects of image-guided ablation therapy.

Follow-up after percutaneous radiofrequency ablation of renal cell carcinoma: contrast-enhanced sonography versus contrast-enhanced CT or MRI.

OBJECTIVE: The purpose of this study was to assess, with contrast-enhanced CT or MRI as the reference imaging technique, the diagnostic performance of low-mechanical-index contrast-enhanced sonography in detecting local tumor progression after percutaneous radiofrequency ablation of renal tumors. MATERIALS AND METHODS: Twenty-nine patients with 30 renal tumors (18 men, 11 women; mean age, 73 years; range, 53-83 years) underwent percutaneous radiofrequency ablation at a single center between March 1998 and January 2007. The imaging follow-up schedule was both contrast-enhanced sonography and CT or MRI 4 months after completion of treatment and every 4 months for the first year. Thereafter, the follow-up schedule was contrast-enhanced sonography every 4 months with CT or MRI every 8 months. The chi-square test with Yates correction was used to evaluate positive and negative predictive values and accuracy. RESULTS: One patient was scheduled to undergo surgical resection, and another patient was lost to follow-up. Twenty-seven patients with 28 renal tumors participated in follow-up. The concordance between contrast-enhanced sonographic and CT or MRI findings was 100% for 27 of 28 tumors (96.4%) that had a hypervascular pattern before treatment. In the case of the tumor that was hypovascular at imaging performed before percutaneous radiofrequency ablation, local tumor progression was missed at contrast-enhanced sonography. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of contrast-enhanced sonography were 96.6%, 100%, 100%, 95.8%, and 98.1%. CONCLUSION: Contrast-enhanced sonography is an effective alternative to CT and MRI in the follow-up of renal tumors managed with percutaneous radiofrequency ablation.

Radiofrequency ablation of liver tumors: the role of microbubble ultrasound contrast agents.

Radiofrequency ablation (RFA) is currently indicated for the treatment of primary and metastatic hepatic malignancies. Real-time ultrasound (US) is generally used during the procedure to guide electrode placement, but for evaluating the results of treatment, contrast-enhanced computed tomography and magnetic resonance imaging have traditionally been considered more effective. This view has changed, however, with the recent development of contrast-enhanced ultrasound (CEUS) (eg, using sulfur hexafluoride microbubbles), which can provide valuable information on the effects of RFA more rapidly and economically than computed tomography or magnetic resonance imaging without exposing the patient to ionizing radiation. In our center, CEUS is performed in patients with liver tumors before and immediately after RFA, in selected cases during the procedure as well, and in the follow-up. Between January 2003 and June 2005, we performed CEUS on 350 patients scheduled for RFA of primary or metastatic liver tumors. In 14 (13.4%) of the 96 patients whose disease was metastatic, CEUS revealed lesions that had been missed on the conventional US examination. In most of these cases, the result was a more complete treatment performed under CEUS guidance. In the remaining 2 (14%) of 14, the results of the examination allowed us to avoid subjecting the patient to useless treatment. In our experience, the use of CEUS also improved the management and follow-up of patients undergoing interstitial therapy.

Treatment with stem cell differentiation stage factors of intermediate-advanced hepatocellular carcinoma: an open randomized clinical trial.

There is no standard treatment for patients with advanced hepatocellular carcinoma (HCC). We developed a product containing stem cells differentiation stage factors (SCDSF) that inhibits tumor growth in vivo and in vitro. The aim of this open randomized study was to assess its efficacy in patients with HCC not suitable for resection, transplantation, ablation therapy, or arterial chemoembolization. A total of 179 consecutive patients were enrolled. We randomly assigned the patients to receive either SCDSF or only conservative treatment. Primary end points were tumor response and survival. Secondary end points were performance status and patient tolerance. Randomization was stopped at the second interim analysis (6 months) of the first 32 patients recruited when the inspection detected a significant difference in favor of treatment (p = 0.037). The responses to the therapy obtained in 154 additional patients confirmed previous results. Evaluation of survival showed a significant difference between the group of patients who responded to treatment versus the group with progression of disease (p < 0.001). Of the 23 treated patients with a performance status (PS) of 1, 19 changed to 0. The study indicated the efficacy of SCDSF treatment of the patients with intermediate-advanced HCC.

Treatment of hepatocellular carcinoma by percutaneous interventional methods.

In the treatment of early and intermediate hepatocellular carcinoma the range of indications for percutaneous ablation techniques is becoming wider than surgery or intra-arterial therapies. Indeed, whereas for some years only patients with up to three small tumors were treated, with the introduction of the single-session technique performed under general anesthesia, even patients with more advanced disease are now being treated. Although it is understood that partial resection assures the highest local control, the survival rates after surgery are roughly comparable with percutaneous ethanol injection. The explanation is due to a balance among advantages and disadvantages of the two therapies. Percutaneous ethanol injection survival curves are better than curves of resected patients who present adverse prognostic factors, and this means that surgery needs a better selection of the patients. Indications for both of these therapies are reported. An open question remains about the choice between percutaneous ethanol injection and other new ablation procedures. In our department we currently use radiofrequency ablation in the majority of patients but consider percutaneous ethanol injection and segmental transarterial chemoembolization complementary, and use them according to the features of the disease and the response. Evaluation of their therapeutic efficacy, techniques and results are reported.

Complications of microwave ablation for liver tumors: results of a multicenter study.

PURPOSE: New technologies for microwave ablation (MWA) have been conceived, designed to achieve larger areas of necrosis compared with radiofrequency ablation (RFA). The purpose of this study was to report complications by using this technique in patients with focal liver cancer. METHODS: Members of 14 Italian centers used a 2.45-GMHz generator delivering energy through a cooled miniature-choke MW antenna and a standardized protocol for follow-up. They completed a questionnaire regarding number and type of deaths, major and minor complications and side effects, and likelihood of their relationship to the procedure. Enrollment included 736 patients with 1.037 lesions: 522 had hepatocellular carcinoma with cirrhosis, 187 had metastases predominantly from colorectal cancer, and 27 had cholangiocellular carcinoma. Tumor size ranged from 0.5 to 10 cm. In 13 centers, the approach used was percutaneous, in 4 videolaparoscopic, and in 3 laparotomic. RESULTS: No deaths were reported. Major complications occurred in 22 cases (2.9%), and minor complications in 54 patients (7.3%). Complications of MWA do not differ from those RFA, both being based on the heat damage. CONCLUSION: Results of this multicenter study confirmed those of single-center experiences, indicating that MWA is a safe procedure, with no mortality and a low rate of major complications. The low rate of complications was probably due to precautions adopted, knowing in advance possible risk conditions, on the basis of prior RFA experience.

Radiofrequency ablation of hepatocellular carcinoma.

Radiofrequency ablation (RFA), usually performed under percutaneous ultrasound guidance, is considered the gold standard among minimally invasive therapies. On the strength of some recent randomized trials, its indications include operable patients with small hepatocellular carcinoma and inoperable patients with more advanced disease also in combination with other therapies. RFA has lower complication rates and costs less than surgery.

Complete response in 5 out of 38 patients with advanced hepatocellular carcinoma treated with stem cell differentiation stage factors: case reports from a single centre.

Hepatocellular carcinoma (HCC) represents the third cause of cancer-related death. Because HCC is multi-centric with time, excluding the few transplanted patients, sooner or later it becomes untreatable with loco-regional therapies and, until some years ago, it was not responsive to systemic therapies. In 2005 a randomized trial indicated the efficacy of a product containing stem cell differentiation stage factors (SCDSF) taken from zebra fish embryos during the stage in which the totipotent stem cells are differentiating into the pluripotent adult stem cells. In such a trial the patients, with "intermediate" and "advanced" HCC according to BCLC/AASLD guidelines, presented benefit in terms of performance status (PS) and objective tumoral response, with some cases (2.4%) of complete response (CR). The aim of this cohort study is to report the experience of a tertiary referral center on the evidence of cases of CR in patients with "advanced" stage HCC treated with SCDSF as supportive care. CR was regarded as sustained disappearance of the neoplastic areas or blood supply therein, accompanied by normalization of AFP levels. Out of 49 patients consecutively recruited and retrospectively evaluated, 38 had "advanced" stage and 11 "terminal" stage. In 5 patients with "advanced" stage a sustained CR was reported (13.1%). Improvement on PS was obtained in 17 patients (34.6%). No side effects occurred. SCDSF treatment confirmed its efficacy in patients with "advanced" HCC, in terms of PS and tumoral response.

Single HCC smaller than 2 cm: surgery or ablation: interventional oncologist's perspective.

In the EASL and AASLD guidelines, hepatic resection (HR) is considered the first option for patients in stage 0 (very early HCC). This statement was not based on randomized controlled trials (RCTs) versus other therapies, but on the oncological assumption that HR is the better procedure for obtaining complete tumor ablation including a safety margin. Subsequently, three RCTs compared percutaneous radiofrequency ablation (RFA) versus HR in patients with early HCC. All failed to demonstrate better survival in favor of HR, even though the larger size of the early stage needs a larger area of necrosis. A recent study focused on stage 0 demonstrated a sustained local complete response after RFA comparable with that of HR. All these trials established that RFA is less invasive and associated with lower complication rates and lower costs. These data suggest that RFA can be considered the first option for operable patients with very early HCC. Other options (HR, PEI, selective TAE/TACE) can be used as salvage therapy for the few cases in which RFA is unsuccessful or unfeasible.

Image-guided tumor ablation: standardization of terminology and reporting criteria.

The field of interventional oncology with use of image-guided tumor ablation requires standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison between treatments that use different technologies, such as chemical (ethanol or acetic acid) ablation, and thermal therapies, such as radiofrequency (RF), laser, microwave, ultrasound, and cryoablation. This document provides a framework that will hopefully facilitate the clearest communication between investigators and will provide the greatest flexibility in comparison between the many new, exciting, and emerging technologies. An appropriate vehicle for reporting the various aspects of image-guided ablation therapy, including classification of therapies and procedure terms, appropriate descriptors of imaging guidance, and terminology to define imaging and pathologic findings, are outlined. Methods for standardizing the reporting of follow-up findings and complications and other important aspects that require attention when reporting clinical results are addressed. It is the group's intention that adherence to the recommendations will facilitate achievement of the group's main objective: improved precision and communication in this field that lead to more accurate comparison of technologies and results and, ultimately, to improved patient outcomes. The intent of this standardization of terminology is to provide an appropriate vehicle for reporting the various aspects of image-guided ablation therapy.

Image-guided tumor ablation: standardization of terminology and reporting criteria.

The field of interventional oncology with use of image-guided tumor ablation requires standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison between treatments that use different technologies, such as chemical (ethanol or acetic acid) ablation, and thermal therapies, such as radiofrequency, laser, microwave, ultrasound, and cryoablation. This document provides a framework that will hopefully facilitate the clearest communication between investigators and will provide the greatest flexibility in comparison between the many new, exciting, and emerging technologies. An appropriate vehicle for reporting the various aspects of image-guided ablation therapy, including classification of therapies and procedure terms, appropriate descriptors of imaging guidance, and terminology to define imaging and pathologic findings, are outlined. Methods for standardizing the reporting of follow-up findings and complications and other important aspects that require attention when reporting clinical results are addressed. It is the group's intention that adherence to the recommendations will facilitate achievement of the group's main objective: improved precision and communication in this field that lead to more accurate comparison of technologies and results and, ultimately, to improved patient outcomes.

Radiofrequency ablation, PEIT, and TACE for hepatocellular carcinoma.

At detection or over time, hepatocellular carcinoma(HCC) is multicentric in origin, against a background of chronic hepatic disease at different stages. Orthotopic liver transplantation (OLT) is the only therapy able to definitely cure both diseases. When OLT is not feasible, all other options can be only palliative. Owing to the multicentricity, surgical resection may be one possible option at the initial detection in selected patients, whereas percutaneous interventional techniques (percutaneous ethanol injection [PEI], radiofrequency ablation [RFA], selected transcatheter arterial chemoembolization [TACE]) are the options more of tenused. The range of their indications is becoming wider. Although it is understood that partial resection assures the greatest local control, the survival rates after surgery are roughly comparable with those obtained with PEI. The explanation for this result reflects a balance among the advantages and disadvantages of the two therapies. PEI survival curves are better than curves of resected patients who present with adverse prognostic factors, and this means that a better selection of the patients for surgery is needed. An open question remains the choice among percutaneous techniques. In our department we currently use RFA in most patients but consider PEI and selected TACE complementary, and use them according to the features of the disease and the response.