Treatment of liver metastases from colorectal cancer with hepatic artery occlusion, intraportal 5-fluorouracil infusion, and oral allopurinol. A randomized clinical trial. Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy--an intergroup study. Comparative study of resection and radiofrequency ablation in the treatment of solitary colorectal liver metastases. Clinical outcomes of hepatic resection and radiofrequency ablation in patients with solitary colorectal liver metastasis. Rates and patterns of recurrence for percutaneous radiofrequency ablation and open wedge resection for solitary colorectal liver metastasis. Prophylactic hepatic arterial infusion chemotherapy for the prevention of liver metastasis in patients with colon carcinoma: a randomized control trial. Solitary colorectal liver metastasis: resection determines outcome. Comparison of resection and radiofrequency ablation for treatment of solitary colorectal liver metastases. Small hepatocellular carcinoma in cirrhosis: randomized comparison of radio-frequency thermal ablation versus percutaneous ethanol injection.
Regional therapy for colorectal liver metastases aimed at prolonging survival has not been tested fully in a randomized trial with untreated control subjects. This study explored the efficacy of temporary hepatic artery occlusion followed by intraportal infusion of 5-fluorouracil (5-FU) and oral allopurinol as biochemical modulators in prolonging the survival of patients with nonresectable liver metastases and no extrahepatic cancer.
                Eighty-four patients were considered for randomization, of whom 24 were excluded at laparotomy because of extrahepatic cancer (n = 17) or resectable lesions (n = 5). In two patients, no cancer was identified in the liver. Thirty-two patients were allocated to receive treatment, and 28 were allocated to receive no regional or systemic treatment. Six patients were excluded after randomization because of major protocol violations.
                The median survival time for patients was 17 months (range, 0-66), and for control subjects, the median was 8 months (range, 0-31). Log rank analysis demonstrated a significant survival benefit for treatment versus no treatment (P = 0.0039). (In two patients, early death was due to toxicity from the wrong dose of 5-FU and the wrong route of administration, respectively; the mean and median survival were reduced by 1 month).
                This study identified a treatment modality that prolongs survival in patients with nonresectable liver metastases and no extrahepatic metastases from colorectal cancer, suggesting that control subjects receiving no therapy may not be necessary in future randomized trials. Despite technical improvements that have minimized the morbidity and mortality of hepatic surgery, the long-term outcome of resection of hepatic metastases of colorectal cancer remains poor, with the majority of patients experiencing treatment failure in the liver. Because arterial chemotherapy regimens targeted to the liver have demonstrated high response rates, an intergroup trial of adjuvant therapy for patients undergoing hepatic resection of liver metastases from colorectal cancer was initiated.
                Patients with one to three potentially resectable metastases were randomized preoperatively to receive no further therapy (control arm, 56 patients) or postoperative hepatic arterial floxuridine combined with intravenous continuous-infusion fluorouracil (chemotherapy arm, 53 patients). After exclusion of patients identified as ineligible for the planned treatment at the time of surgery, there were 45 control patients and 30 on the chemotherapy arm. The study was powered to evaluate improvement in time to recurrence and hepatic disease-free survival, not overall survival.
                The 4-year recurrence-free rate was 25% for the control arm and 46% for the chemotherapy group (P =.04). The 4-year liver recurrence-free rate was 43% in the control group and 67% in the chemotherapy group (P =.03). The median survival of the 75 assessable patients was 49 months for the control arm and 63.7 months for the chemotherapy arm (P =.60). The median survival of all 109 patients was 47 months for the control arm compared with 34 months for the chemotherapy arm (P =.19)
                These data demonstrate that adjuvant intra-arterial and intravenous chemotherapy was beneficial in prolonging time to recurrence and pre-venting hepatic recurrence after hepatic resection of colorectal cancer. We compared outcomes in patients with solitary colorectal liver metastases treated by either hepatic resection (HR) or radiofrequency ablation (RFA).
                A retrospective analysis from a prospective database was performed on 67 consecutive patients with solitary colorectal liver metastases treated by either HR or RFA.
                Forty-two patients underwent HR and 25 patients underwent RFA. The 5-year overall and local recurrence-free survival rates after HR (50.1% and 89.7%, respectively) were higher than after RFA (25.5% and 69.7%, respectively) (P = .0263 and .028, respectively). In small tumors less than 3 cm (n = 38), the 5-year survival rates between HR and RFA were similar, including overall (56.1% vs 55.4%, P = .451) and local recurrence-free (95.7% vs 85.6%, P = .304) survival rates. On multivariate analysis, tumor size, metastases treatment, and primary node status were significant prognostic factors.
                HR had better outcomes than RFA for recurrence and survival after treatment of solitary colorectal liver metastases. However, in tumors smaller than 3 cm, RFA can be recommended as an alternative treatment to patients who are not candidates for surgery because the liver metastases is poorly located anatomically, the functional hepatic reserve after a resection would be insufficient, the patient's comorbidity inhibits a major surgery, or extrahepatic metastases are present. The role of the radiofrequency ablation (RFA) in treatment of solitary liver metastasis has not been established yet. Both hepatic resection (HR) and RFA have been used increasingly in the treatment of colorectal liver metastases.
                A systemic review was performed to determine the impact of treatment modality of solitary liver metastasis on recurrence patterns, disease-free survival, and overall survival (OS) rates.
                Solitary liver metastases were treated by HR in 116 patients (75.8%) and 37 patients (24.2%) were treated with RFA. Prognostic factors, recurrence rate, recurrence patterns, and survival rates were analyzed. The cumulative 3-year and 5-year local recurrence free survival rates were markedly higher in the HR group (88.0% and 84.6%) as compared with those in the RFA group [53.3% and 42.6%, respectively (P</=0.001)]. The 5-year OS rate was lower in the RFA group as compared with the HR group without statistical significance (5-year OS, 65.7% in the HR, 48.5% in the RFA group, P=0.227).
                Despite of higher local recurrence rate, RFA may be considered as a therapeutic option for patients who are considered unsuitable for conventional surgical treatment. Randomized prospective controlled trials comparing the therapeutic outcome of RFA and HR are definitely warranted. The purpose of this study was to compare rates and patterns of disease progression following percutaneous, image-guided radiofrequency ablation (RFA) and nonanatomic wedge resection for solitary colorectal liver metastases.
                We identified 30 patients who underwent nonanatomic wedge resection for solitary liver metastases and 22 patients who underwent percutaneous RFA because of prior major hepatectomy (50%), major medical comorbidities (41%), or relative unresectability (9%). Serial imaging studies were retrospectively reviewed for evidence of local tumor progression.
                Patients in the RFA group were more likely to have undergone prior liver resection, to have a disease-free interval greater than 1 year, and to have had an abnormal carcinoembryonic antigen (CEA) level before treatment. Two-year local tumor progression-free survival (PFS) was 88% in the Wedge group and 41% in the RFA group. Two patients in the RFA group underwent re-ablation, and two patients underwent resection to improve the 2-year local tumor disease-free survival to 55%. Approximately 30% of patients in each group presented with distant metastasis as a component of their first recurrence. Median overall survival from the time of resection was 80 months in the Wedge group vs 31 months in the RFA group. However, overall survival from the time of treatment of the colorectal primary was not significantly different between the two groups.
                Local tumor progression is common after percutaneous RFA. Surgical resection remains the gold standard treatment for patients who are candidates for resection. For patients who are poor candidates for resection, RFA may help to manage local disease, but close follow-up and retreatment are necessary to achieve optimal results. The liver is the most frequent site of recurrence after curative resection in patients with colon carcinoma. For liver metastasis, a high response rate can be achieved with hepatic arterial infusion (HAI) chemotherapy. In the current study, the authors administered 5-fluorouracil (5-FU) as adjuvant chemotherapy by HAI to patients with colon carcinoma without liver metastases and studied its effects on recurrence in the liver and survival.
                A total of 316 patients with preoperative Stage II or Stage III colon carcinoma (according to the 1997 revision of the International Union Against Cancer TNM staging system) were randomly assigned to receive surgery plus 3-week continuous HAI of 5-FU or surgery alone. There were 305 eligible patients, of whom the 119 patients assigned to the HAI arm actually received 5-FU. The primary endpoint was disease-free survival, whereas the secondary endpoints were overall survival and liver metastasis-free survival. Analysis was by intent to treat.
                There were no significant differences noted in morbidity between the two treatment arms. During the follow-up period (median, 59.0 months), the incidence of liver metastasis was significantly decreased in the HAI arm whereas there were no significant differences reported between the 2 arms with regard to the frequency of metastasis at other sites. In the HAI arm, the risk ratio for recurrence was 0.40 (95% confidence interval [95% CI], 0.24-0.64; P=0.0002), the risk ratio for death was 0.37 (95% CI, 0.21-0.67; P=0.0009), and the risk ratio for liver metastasis was 0.38 (95% CI, 0.22-0.66; P=0.0005). These differences were found to be significant only for patients with Stage III disease. Toxicities were mild.
                A schedule of 3-week HAI of 5-FU given as adjuvant chemotherapy to patients with Stage III colon carcinoma appeared to contribute to a significant decrease in the frequency of liver metastases and was associated with an improved survival rate.
                Copyright 2003 American Cancer Society. Hepatic resection (HR) and radiofrequency ablation (RFA) have been proposed as equivalent treatments for colorectal liver metastasis.
                Recurrence patterns after HR and RFA for solitary liver metastasis are similar.
                Analysis of a prospective database at a tertiary care center with systematic review of follow-up imaging in all of the patients.
                Patients with solitary liver metastasis as the first site of metastasis treated for cure by HR or RFA were studied (patients received no prior liver-directed therapy). Prognostic factors, recurrence patterns, and survival rates were analyzed.
                Of the 180 patients who were studied, 150 underwent HR and 30 underwent RFA. Radiofrequency ablation was used when resection would leave an inadequate liver remnant (20 patients) or comorbidity precluded safe HR (10 patients). Tumor size and treatment determined recurrence and survival. The local recurrence (LR) rate was markedly lower after HR (5%) than after RFA (37%) (P<.001). Treatment by HR was associated with longer 5-year survival rates than RFA, including LR-free (92% vs 60%, respectively; P<.001), disease-free (50% vs 0%, respectively; P = .001), and overall (71% vs 27%, respectively; P<.001) survival rates. In the subset with tumors 3 cm or larger (n = 79), LR occurred more frequently following RFA (31%) than after HR (3%) (P = .001), with a 5-year LR-free survival rate of 66% after RFA vs 97% after HR (P<.001). Patients with small tumors experienced longer 5-year overall survival rates after HR (72%) as compared with RFA (18%) (P = .006).
                The survival rate following HR of solitary colorectal liver metastasis exceeds 70% at 5 years. Radiofrequency ablation for solitary metastasis is associated with a markedly higher LR rate and shorter recurrence-free and overall survival rates compared with HR, even when small lesions (< or = 3 cm) are considered. Every method should be considered to achieve resection of solitary colorectal liver metastasis, including referral to a specialty center, extended hepatectomy, and chemotherapy. 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.
                Copyright 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. To compare the effectiveness of radio-frequency (RF) thermal ablation with that of percutaneous ethanol injection (PEI) for the treatment of small hepatocellular carcinoma (HCC) in patients with cirrhosis.
                A series of 102 patients with hepatic cirrhosis and either single HCC 5 cm in diameter or smaller or as many as three HCCs each 3 cm or smaller (overall number of lesions, 142) randomly received either RF ablation (n = 52) or PEI (n = 50) as the sole first-line anticancer treatment. Mean follow-up was 22.9 months +/- 9.4 (SD) in the RF group and 22.4 months +/- 8.6 in the PEI group. Prognostic value of treatment techniques was assessed with univariate and multivariate Cox proportional hazards regression models.
                One- and 2-year survival rates were 100% and 98% in the RF group and 96% and 88% in the PEI group, respectively (univariate relative risk [RR] = 0.20; 95% CI: 0.02, 1.69; P =.138). One- and 2-year local recurrence-free survival rates were 98% and 96% in the RF group and 83% and 62% in the PEI group, respectively (univariate RR = 0.17; 95% CI: 0.06, 0.51; P =.002). One- and 2-year event-free survival rates were 86% and 64% for the RF group and 77% and 43% for the PEI group, respectively (univariate RR = 0.48; 95% CI: 0.27, 0.85; P =.012). RF treatment was confirmed as an independent prognostic factor for local recurrence-free survival rates with multivariate analysis (adjusted RR = 0.20; 95% CI: 0.05, 0.73; P =.015).
                RF ablation is superior to PEI with respect to local recurrence-free survival rates.
The single study included in this review provides very limited evidence to support the effectiveness of one intervention over the other. The authors conclude that local ablative therapies might be useful for the management of liver metastases, but more research is required to further evaluate the effects of these treatment options and their potential role in increasing disease-free survival and in decreasing recurrence rates.