RADIOFREQUENCY ABLATION AS PART OF INTRAHEPATIC TREATMENT STRATEGIES.

Combined liver resection and radiofrequency ablation for bilobar multiple colorectal liver metastasis

Radiofrequency versus microwave ablation for intraoperative treatment of colorectal liver metastases

BackgroundNo randomized controlled trial (RCT) has yet been performed to provide the evidence to clarify the therapeutic debate on liver resection (LR) and radiofrequency ablation (RFA) in treating colorectal liver metastases (CLM). The meta-analysis was performed to summarize the evidence mostly from retrospective clinical trials and to investigate the effect of LR and RFA.Methodology/Principal FindingsSystematic literature search of clinical studies was carried out to compare RFA and LR for CLM in Pubmed, Embase and the Cochrane Library Central databases. The meta-analysis was performed using risk ratio (RR) and random effect model, in which 95% confidence intervals (95% CI) for RR were calculated. Primary outcomes were the overall survival (OS) and disease-free survival (DFS) at 3 and 5 years plus mortality and morbidity. 1 prospective study and 12 retrospective studies were finally eligible for meta-analysis. LR was significantly superior to RFA in 3 -year OS (RR 1.377, 95% CI: 1.246–1.522); 5-year OS (RR: 1.474, 95%CI: 1.284–1.692); 3-year DFS (RR 1.735, 95% CI: 1.483–2.029) and 5-year DFS (RR 2.227, 95% CI: 1.823–2.720). The postoperative morbidity was higher in LR (RR: 2.495, 95% CI: 1.881–3.308), but no significant difference was found in mortality between LR and RFA. The data from the 3 subgroups (tumor<3 cm; solitary tumor; open surgery or laparoscopic approach) showed significantly better OS and DFS in patients who received surgical resection.Conclusions/SignificancesAlthough multiple confounders exist in the clinical trials especially the bias in patient selection, LR was significantly superior to RFA in the treatment of CLM, even when conditions limited to tumor<3 cm, solitary tumor and open surgery or laparoscopic (lap) approach. Therefore, caution should be taken when treating CLM with RFA before more supportive evidences for RFA from RCTs are obtained.

Liver resection is the treatment of choice for patients with solitary colorectal liver metastases. In recent years, however, radiofrequency ablation has been used increasingly in the treatment of colorectal liver metastases. In the absence of randomized clinical trials, this study aimed to compare outcome in patients with solitary colorectal liver metastases treated by surgery or by radiofrequency ablation. Solitary colorectal liver metastases were treated by radiofrequency destruction in 25 patients. The indications were extrahepatic disease in seven, vessel contiguity in nine and co-morbidity in nine patients. Outcome was compared with that of 20 patients who were treated by liver resection for solitary metastases and had no evidence of extrahepatic disease. Most patients in both groups also received systemic chemotherapy. Median survival after liver resection was 41 (range 0-97) months with a 3-year survival rate of 55.4 per cent. There was one postoperative death and morbidity was minimal. Median survival after radiofrequency ablation was 37 (range 9-67) months with a 3-year survival rate of 52.6 per cent. Survival after resection and radiofrequency ablation of solitary colorectal liver metastases was comparable. The latter is less invasive and requires either an overnight stay or day-case facilities only.

Objective To compare the efficacy of radiofrequency ablation versus surgical resection in treatment of colorectal liver metastases with a maximum diameter ≤ 3 cm and a number ≤ 3, and to analyze the risk factors of recurrence. Methods The data of 97 patients with colorectal liver metastases from January 2012 to June 2016 treated at Tianjin Medical University Cancer Institute and Hospital were analyzed retrospectively. There were 66 males and 31 females. The patients were divided into the radiofrequency ablation group (23 patients) and the surgical resection group (74 patients). The patients were followed up. The clinicopathological features of the two groups before treatment were compared. Kaplan-Meier curves were drawn, and the recurrence-free survival curve and overall survival curve of the two groups were compared by log-rank test. Univariate and multivariate Cox regression analysis was used to analyze the risk factors of recurrence. Results There were no significant differences in age, location of primary tumor, number and size of liver metastases, and preoperative carcinoembryonic antigen level between the two groups (P>0.05). On the date this study was censored, there were 50 patients who had developed recurrence in the surgical resection group and 22 patients in the ablation group, (67.6% vs. 95.7%). The difference was significant (P 0.05). Univariate and multivariate analysis showed that N 1~2 staging (HR=1.908, 95%CI: 1.094~3.325), simultaneous liver metastasis (HR=1.662, 95%CI: 1.024~2.695) and radiofrequency ablation (HR=2.708, 95%CI: 1.589~4.617) were independent risk factors of recurrence for colorectal liver metastasis. Conclusions Radiofrequency ablation can achieve complete ablation in patients with colorectal liver metastases with maximum diameter ≤ 3 cm and number ≤ 3, but the recurrence rate of radiofrequency ablation is significantly higher than that of surgical resection. N 1~2 staging, simultaneous liver metastasis and radiofrequency ablation were independent risk factors for recurrence of colorectal liver metastasis. Key words: Colorectal neoplasms; Neoplasm metastasis; Liver neoplasm; Surgical procedures, operative; Radiofrequency ablation

A commentary on “The prognosis of radiofrequency ablation versus hepatic resection for patients with colorectal liver metastases: A systematic review and meta-analysis based on 22 studies” (Int J Surg 2021;87:105896)

Radiofrequency ablation is a new invasive procedure that is being increasingly used in the treatment of colorectal liver metastases. Resection as the only potential cure for colorectal liver metastases is limited by the size and the itrahepatic localization of lesions. Radiofrequency ablation may extend the limitations of classic surgery. In this work we analyzed the combination of surgical liver resection and radiofrequency ablation of liver metastases. This study included 11 patients with colorectal metastases. Colon resection and radiofrequency ablation have been performed in five (5) patients, three (3) patients underwent liver resection and radiofrequency ablation, and in three (3) patients colon resection, liver resection and radiofrequency ablation were performed. In our study group, there were 6 (54.54%) men and 5 (45.45%) women aged 55 to 66 years and 52 to 67 years of age, respectively. During operations, we treated 30 liver metastases, 2.72 metastses per patient. There were from 2 to 4 ablation metastases. The diameter of colorectal metastases was between 11 mm and 44 mm. Most of ablation metastases (12 or 40%) were between 2.1 cm and 3 cm in diameter. Only 10% of ablation metastases were over 40 mm in diameter. The majority of patients with metastatic colorectal hepatic tumors are not candidates for surgical resection, due to tumor size, location and multifocality. However, we can treat advanced colorectal cancers and colorectal liver metastases with a combination of liver resection and radiofreqency ablation. In this way we can operate and give a chance to patients with multifocal metastases and metastases with a diametar over 40 mm. A combination of liver resection and radiofrequency ablation in treatment of advanced colorectal cancers with liver metastases is a good treatment modality which increases the number of operabile cases.

Liver transplantation (Lt) for colorectal cancer (CRC) liver metastases is no more considered due to the poor outcome observed up to the 1990s. According to the European Liver Transplant Registry (ELTR), 1- and 5-year patient survival following Lt for CRC liver metastases performed prior to 1995 was 62% and 18%, respectively. However, 44% of graft loss or patient deaths were not related to tumor recurrence. Over the last 20 years there has been dramatic progress in patient survival after Lt, thus it could be anticipated that survival after Lt for CRC secondaries today would exceed from far, the outcome of the past experience. By utilizing new imaging techniques for proper patient selection, modern chemotherapy and aggressive multimodal treatment against metastases, long term survivors and even cure could be expected. Preliminary data from a pilot study show an overall survival rate of 94% after a median follow up of 25 months. While long term survival after the first Lt is 80% all indications confounded, 5-year survival after repeat Lt is no more than 50% to 55%. If patients transplanted for CRC secondaries can reach the latter survival rate, it could be difficult to discriminate them in the liver allocation system and live donation could be an option.

A systematic review on the clinical benefit and role of radiofrequency ablation as treatment of colorectal liver metastases

Local radiofrequency ablation techniques for liver metastases of colorectal cancer

BackgroundAt present, there are no widely accepted criteria for the use of radiofrequency ablation (RFA) for the treatment of colorectal liver metastases (CLM) in the context of effective modern-agent therapies. We aimed to define selection criteria for patients with liver-limited CLM who may benefit from adding RFA to systemic therapy with respect to long-term disease control.MethodsBetween 2002 and 2007, 88 consecutive patients received RFA for liver-only CLM during partial remission (PR), stable disease (SD), or progressive disease (PD) after systemic therapy. At a median follow-up of 8.2 years (range 5.2-11.1 years), clinical data were correlated to overall survival (OS) and recurrence-free survival (RFS).ResultsPoor OS and RFS correlated significantly with PD to systemic therapy before RFA (HR 5.46; p < 0.0001; and HR 6.46; p < 0.0001), number of ≥4 CLM (HR 3.13; p = 0.0005; and HR 1.77; p = 0.0389), and carcinoembryonic antigen (CEA) level of ≥100 ng/ml (HR 1.67; p = 0.032; and HR 1.67; p = 0.044). The presence of four criteria (PR, ≤3 CLM, ≤3 cm maximum size, and CEA ≤100 ng/ml) selected a subgroup (n = 23) with significantly higher probabilities for OS and RFS at 5 years (39% and 22%,respectively) compared to those without any or up 3 of these criteria (0-27% and 0-9%, p < 0.001, respectively).ConclusionsA score based on four criteria (response to systemic therapy, ≤3 CLM, ≤3 cm size, low CEA value) may allow to select patients with liver-only CLM for whom additional use of RFA most likely adds benefit in an attempt to achieve long-term disease control. Almost one-fourth of patients fulfilling these four criteria may achieve 5-year survival without disease recurrence following effective systemic plus local RFA treatment.

The use of radiofrequency ablation (RFA) for the treatment of colorectal liver metastases has been approved by the US Food and Drug Administration for several years, and this therapy is now being adopted worldwide. However, US Food and Drug Administration approval of medical devices and techniques relates only to safety and feasibility, and does not relate to proven clinical benefit, which is necessary for approval of new drugs and their indications. RFA appears to be beneficial in the treatment of primary hepatocellular carcinoma, where its use has received the tentative support of the UK National Institute for Clinical Excellence. There is also growing interest in its use at other sites of colorectal cancer, including the treatment of lung metastases. RFA is being used increasingly as an adjunct to surgical resection of colorectal liver metastases, as an alternative to resection if the disease is deemed inoperable at laparotomy, with some authors even arguing equivalence of outcome when compared with surgical resection of low-volume liver disease. With the evolution of more powerful generators (commercial generators can now produce 300 W of energy, sufficient to destroy a sphere of tissue of 6 to 7 cm diameter in 10 to 20 minutes), and better results achieved by hepatic inflow occlusion, the responses of liver tumors to RFA destruction are now highly predictable and reproducible. The report by Berber et al in this issue of Journal of Clinical Oncology, therefore, is both timely and welcome. This study reports one of the largest prospective series of patients with colorectal liver metastases treated with RFA. The authors present an honest and frank assessment of the use of this technique, with the first large-scale study addressing predictive factors for patients undergoing this treatment. By 2003, 1 year after completion of the study period, the widely accepted definition of surgical resectability of colorectal liver metastases was essentially any number of metastases (unior bilobar) as long as no more than 70% of liver (five to six of the eight liver segments) needed to be removed. One might therefore be concerned about the definition of resectability of liver metastases employed at this particular center, in view of the fact that only 44 patients underwent liver resection during the 5-year study period, whereas 328 patients underwent laparoscopic RFA. However, the 135 consecutive patients recruited to the study already fall into a poorer prognostic group, including recurrence after previous liver resection, disease progression while receiving chemotherapy, or presence of extrahepatic disease. The authors are to be congratulated on attempting to perform laparoscopic RFA, rather than percutaneous RFA in patients after previous liver resection, bearing in mind the difficult dissection frequently encountered by experienced liver surgeons at open surgery in these patients. Berber et al have shown that predictive factors for better survival after RFA include a preprocedure serum carcinoembryonic antigen of less than 200 ng/mL, dominant lesion size of less than 3 cm diameter, and three or fewer tumors. Although one might wonder why patients who fell into the latter two groups were not considered for resectional surgery rather than entry to the study, these results are similar prognostic factors for outcome after hepatectomy and cryosurgery for the same condition. Taken together, these results bear out the currently accepted rule of fives (five or fewer tumors, smaller than 5 cm diameter) when selecting patients with colorectal liver metastases for RFA treatment by whatever route of access: percutaneous, laparoscopic, or open surgery. There are concerns about taking the results of the study by Berber et al at face value for two reasons. First, at the time of RFA, 40 of their patients (30%) had extrahepatic disease, which apparently went untreated. In this scenario, one questions the purpose of the RFA regarding whether the treatment intention was to improve the liver computed JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 7 MARCH 1 2005

Repeat liver resection for colorectal liver metastases (CRLMs) is possible in a limited number of patients, with radiofrequency ablation (RFA) as an alternative for unresectable CRLMs. The aim of this study was to analyse survival rates with these interventions. This was a database analysis of patients who underwent first and repeat interventions for synchronous and metachronous CRLMs between 2000 and 2013. Descriptive and survival statistics were calculated. Among 431 patients who underwent resection or RFA for CRLMs, 305 patients developed recurrences for which 160 repeat interventions (resection and/or RFA or ablative radiotherapy) were performed. In total, after 707 first or repeat interventions, 516 recurrences (73·0 per cent) developed, of which 276 were retreated curatively. At the time of first intervention, independent risk factors for death were lymph node-positive primary tumour (hazard ratio (HR) 1·40; P = 0·030), more than one CRLM (HR 1·53; P = 0·007), carcinoembryonic antigen level exceeding 200 ng/ml (HR 1·89; P = 0·020) and size of largest CRLM greater than 5 cm (HR 1·54; P = 0·014). The 5-year overall survival rates for liver resection and percutaneous RFA as first intervention were 51·9 and 53 per cent, with a median overall survival of 65·0 (95 per cent c.i. 47·3 to 82·6) and 62·1 (52·2 to 72·1) months, respectively. RFA had good oncological outcomes in patients with unresectable CRLMs. Radiofrequency ablation is progressively more applied with each additional intervention.

Colorectal liver metastasis (CRLM) is one of the most difficult and key points in the treatment of colorectal cancer. Approximately 50% to 60% of patients diagnosed as colorectal cancer develops metastasis, and 80% to 90% of CRLM is unresectable. Surgical resection is the first-line treatment for CRLM, while it is only suitable for about 15% patients. Systemic chemotherapy can prolong the survival of CRLM patients, however, a part of CRLM patients are resistant to chemotherapy. With the development of technology and the update of clinical evidence, individual therapy with target drugs and multidisciplinary treatment (MDT) have became a tendency, and minimally invasive interventional therapy has gained more acceptance in the MDT mode of the treatment for CRLM. Basically, the interventional treatment for CRLM is divided into two groups: vascular intervention and local minimally invasive intervention. Vascular approaches encompass portal vein embolization (PVE), hepatic artery infusion chemotherapy (HAIC), transarterial chemoembo- lization (TACE), and transarterial radioembolization (TARE). Local minimally invasive intervention includes radiofrequency ablation (RFA), microwave ablation(MWA), cryoablation (CRA), and irreversible electroporation (IRE). Thevefore intervention treatment is an important complement to the comprehensive therapy of CRLM.

Current literature evaluating radiofrequency ablation (RFA) for treatment of colorectal liver metastases describes high-risk surgical candidates or patients with unresectable disease. This creates bias when comparing RFA and hepatic resection. A Markov analysis would define theoretical outcomes necessary for RFA to demonstrate equivalence to resection. A multistate Markov decision analytic model was constructed. Second-order Monte Carlo analysis was used to simulate a randomized controlled trial. Sensitivity analyses were performed to determine the projected outcomes necessary for RFA to achieve equivalence with resection. Tertiary care teaching hospital. A systematic review of published literature was performed, identifying studies involving patients with colorectal liver metastases treated with RFA or resection. Data were also included from a prospective database of patients undergoing laparoscopic RFA at our institution. Percutaneous or laparoscopic RFA and hepatic resection. Quality-adjusted life expectancy and quality of life-adjusted survival. The base-case analysis (60-year-old man) demonstrated a mean ± SD quality-adjusted life expectancy of 5.67 ± 0.71 years and a 5-year survival of 38.2% following resection. Based on current literature, the mean ± SD quality-adjusted life expectancy for RFA was 3.61 ± 0.49 years, with a 5-year survival of 27.2%. Sensitivity analyses demonstrated that RFA becomes the preferred strategy if the median disease-free survival reaches 1.42 years. When limited to patients from our institution with resectable lesions, the quality-adjusted life expectancy for RFA improved to a mean ± SD of 5.72 ± 0.50 years. Classical Markov analysis demonstrates that based on current literature, resection is superior to RFA in the treatment of colorectal liver metastases. When input is limited to laparoscopic RFA in patients with resectable lesions, projected 5-year survival is superior to that of hepatic resection.