Pretreatment Apparent Diffusion Coefficient as a Predictor of Response to Transcatheter Arterial Chemoembolization Immediately Combined with Radiofrequency Ablation for Treatment of Solitary Large Hepatocellular Carcinoma.
Tang Jing,Liu Fengyong,Yuan Hongjun,Li Xin,Tian Xiaomei,Ji Kan,Li Xueping,Wang Wei
Cancer management and research
Purpose:To evaluate whether the pretreatment apparent diffusion coefficient (ADC) measured with diffusion weighted imaging (DWI) of tumor can be used as an imaging biomarker for predicting prognosis in solitary large hepatocellular carcinomas (HCCs) treated with transcatheter arterial chemoembolization (TACE) immediately combined with radiofrequency ablation (RFA). Patients and Methods:In this single institution retrospective study, 40 solitary large HCCs that underwent treatment with TACE immediately combined with RFA were analyzed. All patients underwent abdominal dynamic contrast-enhanced magnetic resonance imaging within one month before treatment with DWI, and ADC values in the lesions were measured by two independent radiologists. Associations among patients' preoperative ADC values and objective response (OR), progression-free survival (PFS) and overall survival (OS) were examined. Survival curves were drawn with the Kaplan-Meier method, and differences were determined with the Log rank test. The Cox proportional-hazards model was used for univariate and multivariate analyses of PFS and OS. Results:Forty solitary large HCCs (mean 9.54 cm, range 5.04-16.06 cm) were successfully treated with TACE in immediate combination with RFA (OR 75%). The ADC values were significantly higher in the response group than the non-response group (1.51±0.32×10 mm/s vs 1.09±0.17×10 mm/s; <0.001). As predicted on the basis of the ADC values, the optimal cutoff value for the efficacy of TACE combined with RFA was 1.32×10 mm/s, with a predictive sensitivity of 0.63 and a specificity of 1.00. Patients with high ADC had longer PFS than those with low ADC (14.9 months vs 5.3 months; <0.001) and had significantly longer survival rates (22.6 months vs 12.1 months; =0.004). Conclusion:Preoperative ADC values <1.32×10 mm/s are an independent predictor of poorer prognosis in patients with solitary large HCCs who have undergone TACE immediately combined with RFA.
What is the difference in ablation zone of multi-bipolar radiofrequency ablation between liver cirrhosis and normal liver background? - a prospective clinical study.
Wang Hong,Lee Jung-Chieh,Cao Kun,Tang He-Wen,Wang Song,Zhang Zhong-Yi,Wu Wei,Yan Kun,Yang Wei
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group
PURPOSE:To explore the differences in ablation zone between liver cirrhosis and normal liver background and investigate the effect of hepatic blood flow on ablation zone of RFA. METHODS:Between 2017 and 2019, 203 patients who had liver malignancies and underwent percutaneous RFA with Celon bipolar electrodes enrolled into this study. There were 90 patients had liver cirrhosis and 113 patients had normal liver background. They were 63 females and 140 males with average age of 59.0 ± 10.9 years old. Contrast-enhanced CT/MRI was used to evaluate the ablation zone in one month after RFA. The hepatic flow measurements on CDFI and CEUS were performed before RFA. Correlations between ablation zone versus hepatic flow were assessed using multiple linear regression analysis. RESULTS:The average ablation zone in cirrhotic liver was significantly larger than those in normal liver background with 3 cm tip of RF electrodes (length 3.5 ± 0.5 vs 3.1 ± 0.4 cm, = 0.001; width 2.6 ± 0.3 vs 2.2 ± 0.3 cm, < 0.001; thickness 2.5 ± 0.3 vs 2.0 ± 0.2 cm, < 0.001). The similar result was found with three 4 cm tip of RF electrodes (width 3.6 ± 0.5 vs 3.1 ± 0.5 cm, = 0.019; thickness 3.3 ± 0.5 vs 2.7 ± 0.5 cm, = 0.002). The multiple linear regression analysis showed arrive time of hepatic vein and portal vein was statistically associated with ablation zone with 3 cm electrodes ( < 0.001, = 0.001), but explained part of the variance (Adjusted R=0.294, adjusted R=0.212). CONCLUSION:The ablation zones of RFA with multi-bipolar electrodes in liver cirrhosis were significantly larger than those in normal liver background, being up to 6 mm in thickness. The hepatic flow parameters partly contributed to the ablation zone.
Radiofrequency ablation versus surgical resection for the treatment of solitary hepatocellular carcinoma 2 cm or smaller: A cohort study in Taiwan.
Wu Chao-Chuan,Tseng Chih-Wei,Tseng Kuo-Chih,Chen Yen-Chih,Wu Ta-Wei,Chang Sou-Yi,Chang Yao-Jen,Chao You-Chen,Hsu Ching-Sheng
Journal of the Formosan Medical Association = Taiwan yi zhi
BACKGROUND/PURPOSE:Radiofrequency ablation (RFA) is increasingly being used instead of surgical resection for the treatment of hepatocellular carcinoma (HCC) tumor measuring ≦2 cm. However, the long-term outcomes of RFA, especially in comparison to surgical resection, are still debated. We compared the outcomes of surgical resection and RFA in patients with a solitary HCC tumor measuring ≦2 cm from a 10-year cohort study. METHODS:From Jan 2006 to Dec 2016, 156 patients with a resectable HCC measuring ≦2 cm who underwent surgical resection (n = 83) or RFA (n = 73) at the Buddhist Tzu Chi Medical Foundation were enrolled. Patient characteristics, overall survival (OS), and recurrence-free survival (RFS) were retrospectively examined, and comparisons were made between the two groups and through subgroup analyses. RESULTS:The 1-year, 3-year, 5-year, and 7-year OS outcomes were comparable between the surgical resection group and the RFA group (P = 0.193), but the surgical resection group had significantly higher 1-year, 3-year, 5-year, 7-year, and 10-year RFS than the RFA group (P = 0.018). Multivariate analysis revealed that patients with lower age, Child-Turcotte-Pugh score, or albumin-bilirubin score before treatment had better OS, and patients with an HCV infection or receiving RFA treatment had higher HCC recurrence rates. CONCLUSION:The liver reserve determined the long-term OS of patients with an HCC tumor ≦ 2 cm, and surgical resection offered better RFS than RFA (ClinicalTrials.gov number, NCT04525833.).
Prognostic Stratification Based on a Novel Nomogram for Solitary Large Hepatocellular Carcinoma After Curative Resection.
Zhuang Hongkai,Zhou Zixuan,Ma Zuyi,Huang Shanzhou,Gong Yuanfeng,Zhang Zedan,Hou Baohua,Yu Weixuan,Zhang Chuanzhao
Frontiers in oncology
Solitary large hepatocellular carcinoma (SLHCC) is a specific subtype of HCC with unique characteristics. It is of great interest to assess and stratify the prognosis of SLHCCs after curative resection. In this study, we tried to construct a prognostic nomogram for SLHCC following curative resection through a retrospective analysis of 202 SLHCC cases. Seven prognostic factors were identified and integrated to establish a novel prognostic nomogram, which included tumor size, microvascular invasion, tumor differentiation, Ki67 (%), α-fetoprotein (AFP), carbohydrate antigen 125 (CA125), and HBsAg status. The Harrell's concordance index (C-index) of the nomogram for overall survival (OS) in the training, validation, and whole sets was 0.752, 0.703, and 0.733, respectively. Furthermore, the area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the nomogram for predicting 1-, 3-, and 5-year OS indicated that the nomogram had an optimal discrimination of the prognostic prediction for SLHCC. The total score of each patient was calculated based on the nomogram, and patients were divided into three subgroups: low-risk group (total score ≦ 107), medium-risk group (107 < total score ≤ 125), and high-risk group (total score > 125). The 1-, 3-, and 5-year OS rates of the low-risk, medium-risk, and high-risk groups in the whole set were 89.3 vs. 70.1 vs. 33.3%, 76.6 vs. 37.8 vs. 14.5%, and 69.8 vs. 25.1 vs. 12.5%, respectively ( < 0.001). Similar results were shown in terms of the recurrence-free survival (RFS) rate. By analyzing 101 cases of recurrent tumors, transarterial chemoembolization (TACE) plus radiofrequency ablation (RFA)/surgery was found to prolong patient survival when compared to TACE alone in the low-risk group, but not in the medium/high-risk group. In conclusion, our prognostic nomogram successfully stratifies the prognosis for SLHCC after curative resection, which deserves further study in future clinical practice.
Microwave Ablation Versus Radiofrequency Ablation for Treatment of Hepatocellular Carcinoma: A Meta-Analysis of Randomized Controlled Trials.
Facciorusso Antonio,Abd El Aziz Mohamed A,Tartaglia Nicola,Ramai Daryl,Mohan Babu P,Cotsoglou Christian,Pusceddu Sara,Giacomelli Luca,Ambrosi Antonio,Sacco Rodolfo
There are limited and discordant results on the comparison between microwave ablation (MWA) and radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC). This meta-analysis aims to compare the two treatments in terms of efficacy and safety, based on a meta-analysis of randomized-controlled trials (RCTs). A computerized bibliographic search was performed on the main databases throughout August 2020. The primary outcome was the complete response rate, while survival rate (at 1-, 2-, 3-, and 5-year), disease-free survival rate (at 1-, 2-, 3-, and 5-year), local and distant recurrence rate, adverse event rate, and number of treatment sessions were the secondary outcomes. Seven RCTs enrolling 921 patients were included. No difference in terms of complete response between the two treatments was observed (risk ratio (RR) 1.01, 95% CI 0.99-1.02). Survival rates were constantly similar, with RRs ranging from 1.05 (0.96-1.15) at 1 year to 0.91 (0.81-1.03) at 5 years. While local recurrence rate was similar between MWA and RFA (RR 0.70, 0.43-1.14), distant recurrence rate was significantly lower with MWA (RR 0.60, 0.39-0.92). Disease-free survival at 1, 2, and 3 years was similar between the two groups with RR 1.00 (0.96-1.04), 0.94 (0.84-1.06), and 1.06 (0.93-1.21), respectively. On the other hand, RR for disease-free survival at 5 years was significantly in favor of MWA (3.66, 1.32-42.27). Adverse event rate was similar between the two treatments (RR 1.06, 0.48-2.34), with bleeding and hematoma representing the most frequent complications. Our results indicate a similar efficacy and safety profile between the two techniques. MWA seems to decrease the rate of long-term recurrences, but this finding needs to be confirmed in further trials.
Pre-radiofrequency ablation MRI imaging features predict the local tumor progression in hepatocellular carcinoma.
Hu Zhouchao,Yu Nannan,Wang Heping,Li Shibo,Yan Jingang,Zhang Guoqiang
ABSTRACT:To investigate whether MRI features could preoperatively predict local tumor progression (LTP) in patients with hepatocellular carcinoma (HCC) treated with radiofrequency ablation (RFA) as the first-line treatment and improve a novel predictive model through developing a nomogram including various conventional MRI parameters. 105 patients with HCCs who had received RFA were enrolled. All patients had undergone conventional MRI before RFA. Uni- and multivariable analyses for LTP were assessing using a Cox proportional hazards model. The developed MRI-based nomogram was further designed based on multivariable logistic analysis in our study and the usefulness of the developed model was validated according to calibration curves and the C-index. Rim enhancement (hazard ratio: 2.689, P = .044) and the apparent diffusion coefficient (ADC) values (hazard ratio: 0.055, P = .038) were statistically significant independent predictors of LTP after RFA at multivariable analysis. The performance of the nomogram incorporating two MRI parameters (with a C-index of 0.782) was improved compared with that based on rim enhancement and ADC alone (with C-index values of 0.630 and 0.728, respectively). The calibration curve of the MRI-based nomogram showed good conformance between evaluation and observation at 0.5, 1, and 1.5 years after RFA. The preliminary predictive model based on MRI findings including rim enhancement and ADC value could be used preoperatively to estimate the risk of LTP of HCC after RFA as the first-line treatment.
Microwave ablation determines similar survival outcomes as compared to radiofrequency ablation for the treatment of hepatocellular carcinoma.
Khan Amer,Mostowy Marcin,Owusu Michael,Mutambanengwe Mercy,Habimana Sam,Bence Somoskoi,Facciorusso Antonio
Expert review of gastroenterology & hepatology
OBJECTIVES:It is still unclear whether microwave ablation (MWA) outperforms radiofrequency ablation (RFA) in the treatment of hepatocellular carcinoma (HCC). Aim of this manuscript is to compare the two treatments through a meta-analysis of randomized-controlled trials (rcts). METHODS:Computerized bibliographic search was performed on main databases through August 2020. The primary outcome was the complete response rate, with survival rate, disease-free survival rate, and adverse event rate as secondary outcomes. Results were expressed in terms of risk ratio (RR) and 95% confidence interval (CI). RESULTS:Seven rcts enrolling 1143 patients were included. Rates of complete response were similar (RR 1.01, 95% CI 0.99-1.02); likewise, survival rates were constantly similar, with rrs ranging from 1.05 (0.96-1.15) at 1-year to 0.91 (0.81-1.03) at 5-year. Disease-free survival at 1-, 2-, and 3-year was similar between the two groups with RR 1.00 (0.96-1.04), 0.94 (0.84-1.06), and 1.06 (0.93-1.21), respectively. On the other hand, RR for disease-free survival at 5-year was significantly in favor of MWA (3.66, 1.32-42.27). Adverse event rate was similar between the two treatments (RR 1.06, 0.48-2.34), with bleeding and hematoma as most frequent complications. CONCLUSIONS:MWA seems to determine similar outcomes as compared to RFA.
Report of the 21st Nationwide Follow-up Survey of Primary Liver Cancer in Japan (2010-2011).
Kudo Masatoshi,Izumi Namiki,Kokudo Norihiro,Sakamoto Michiie,Shiina Shuichiro,Takayama Tadatoshi,Tateishi Ryosuke,Nakashima Osamu,Murakami Takamichi,Matsuyama Yutaka,Takahashi Arata,Miyata Hiroaki,Kubo Shoji
Hepatology research : the official journal of the Japan Society of Hepatology
In the 21st Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 22,134 new patients and 41,956 previously followed patients were compiled from 546 institutions over a 2-year period from 1 January 2010 to 31 December 2011. Basic statistics compiled for patients newly registered in the 21st survey were cause of death, medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathological diagnosis, recurrence status, and autopsy findings. Compared with the previous 20th survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, had more patients with non-B non-C HCC, had smaller tumor diameter, and was more frequently treated with hepatectomy and with radiofrequency ablation. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 1998 and 2011 whose final outcome was survival or death (excluding unknown). Cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter, and Child-Pugh grade) and by treatment type (hepatectomy, local ablation therapy, transcatheter arterial chemoembolization, and hepatic arterial infusion chemotherapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2011 into four time-period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer.
Histological Correlation for Radiofrequency and Microwave Ablation in the Local Control of Hepatocellular Carcinoma (HCC) before Liver Transplantation: A Comprehensive Review.
Habibollahi Peiman,Sheth Rahul A,Cressman Erik N K
Radiofrequency ablation (RFA) and microwave ablation (MWA) are the most widely studied and applied ablation techniques for treating primary and secondary liver tumors. These techniques are considered curative for small hepatic tumors, with post-ablation outcomes most commonly assessed by an imaging follow up. However, there is increasing evidence of a discrepancy between radiological and pathological findings when ablated lesions are evaluated following liver resection or liver transplantation. A comprehensive review of the available literature reporting the complete pathological response (cPR) following RFA and MWA was performed to estimate the success rate and identify the factors associated with treatment failure. Following RFA, cPR is reported in 26-96% of tumors compared to 57-95% with MWA. Larger tumor size and vessels larger than 3 mm adjacent to the treated tumor are the most important factors identified by previous studies associated with viable residual tumors after RFA. Correlating post-ablation radiological studies with pathological findings shows that computed tomography (CT) and magnetic resonance imaging (MRI) have low sensitivity but high specificity for detecting residual viable or recurrent hepatocellular carcinoma (HCC) tumors. There are promising recent reports combining multiprobe ablation techniques with three-dimensional treatment planning software and stereotactic-aiming instrumentation to achieve more than 90% cPR in both small and large HCC tumors. In conclusion, the reported success for achieving cPR in HCC following RFA and MWA is highly variable in different studies and decreases with increasing lesion size and unfavorable tumor characteristics. Very few studies have reported a high rate of cPR. As these studies are single-center and retrospective, they need to be further validated and reproduced in other clinical settings.
Outcomes of radiofrequency ablation as first-line therapy for hepatocellular carcinoma less than 3 cm in potentially transplantable patients.
Doyle Adam,Gorgen Andre,Muaddi Hala,Aravinthan Aloysious D,Issachar Assaf,Mironov Oleg,Zhang Wei,Kachura John,Beecroft Robert,Cleary Sean P,Ghanekar Anand,Greig Paul D,McGilvray Ian D,Selzner Markus,Cattral Mark S,Grant David R,Lilly Leslie B,Selzner Nazia,Renner Eberhard L,Sherman Morris,Sapisochin Gonzalo
Journal of hepatology
BACKGROUND & AIMS:Radiofrequency ablation (RFA) is an effective treatment for single hepatocellular carcinoma (HCC) ≤3 cm. Disease recurrence is common, and in some patients will occur outside transplant criteria. We aimed to assess the incidence and risk factors for recurrence beyond Milan criteria in potentially transplantable patients treated with RFA as first-line therapy. METHODS:We performed a retrospective cohort study of potentially transplantable patients with new diagnoses of unifocal HCC ≤3 cm that underwent RFA as first-line therapy between 2000-2015. We defined potentially transplantable patients as those aged <70 years without any comorbidities that would preclude transplant surgery. Incidence of recurrence beyond Milan criteria was compared across 2 groups according to HCC diameter at the time of ablation: (HCC ≤2 cm vs. HCC >2 cm). Competing risks Cox regression was used to identify predictors of recurrence beyond Milan criteria. RESULTS:We included 301 patients (167 HCC ≤2 cm and 134 HCC >2 cm). Recurrence beyond Milan criteria occurred in 36 (21.6%) and 47 (35.1%) patients in the HCC ≤2 cm and the HCC >2 cm groups, respectively (p = 0.01). The 1-, 3- and 5-year actuarial survival rates after RFA were 98.2%, 86.2% and 79.0% in the HCC ≤2 cm group vs. 93.3%, 77.6% and 70.9% in the HCC >2 cm group (p = 0.01). Tumor size >2 cm (hazard ratio 1.94; 95%CI 1.25-3.02) and alpha-fetoprotein levels at the time of ablation (100-1,000 ng/ml: hazard ratio 2.05; 95%CI 1.10-3.83) were found to be predictors of post-RFA recurrence outside Milan criteria. CONCLUSION:RFA for single HCC ≤3 cm provides excellent short- to medium-term survival. However, we identified patients at higher risk of recurrence beyond Milan criteria. For these patients, liver transplantation should be considered immediately after the first HCC recurrence following RFA. LAY SUMMARY:Radiofrequency ablation and liver transplantation are treatment options for early stages of hepatocellular carcinoma (HCC). After ablation some patients will experience recurrence or metastatic spread of the initial tumor or may develop new tumors within the liver. Despite close follow-up, these recurrences can progress rapidly and exceed transplant criteria, preventing the patient from receiving a transplant. We identified that patients with HCC >2 cm and higher serum alpha-fetoprotein are at greater risk of recurrence beyond the transplant criteria. These data suggest that liver transplantation should be considered immediately after the first HCC recurrence for these patients.
Radiotherapy for Hepatocellular Carcinoma Results in Comparable Survival to Radiofrequency Ablation: A Propensity Score Analysis.
Hara Koji,Takeda Atsuya,Tsurugai Yuichiro,Saigusa Yusuke,Sanuki Naoko,Eriguchi Takahisa,Maeda Shin,Tanaka Katsuaki,Numata Kazushi
Hepatology (Baltimore, Md.)
Potentially curative treatments for early-stage hepatocellular carcinoma (HCC) have drawbacks and contraindications. Recently, radiotherapy has achieved good outcomes. We compared the outcomes of radiotherapy and radiofrequency ablation (RFA) for early-stage HCC. Consecutive patients with ≤3 early-stage HCC lesions and tumor diameters ≤3 cm treated with RFA or radiotherapy were reviewed. RFA was the first choice for HCC unsuitable for surgery. Otherwise, stereotactic body radiotherapy in five fractions was mainly performed. For HCC adjacent to the gastrointestinal tract, radiotherapy with mild hypofractionation was performed. Propensity score matching was performed to reduce the selection bias between the RFA and radiotherapy groups. Between 2012 and 2016, a total of 231 patients with 474 tumors and 143 patients with 221 tumors were eligible and were treated with RFA and radiotherapy, respectively. In an unmatched comparison, the 3-year local recurrence rate was significantly lower for radiotherapy than for RFA (5.3%; 95% confidence interval [CI], 2.7-9.2; versus 12.9%, 95% CI, 9.9-16.2) (P < 0.01). A propensity score matching analysis of 106 patients in each group successfully matched the two treatment groups with regard to Barcelona Clinic Liver Cancer staging, T stage, and tumor size but not the adjacency of the tumor to risk organs or first or salvage treatment. The 3-year overall survival rates for RFA and radiotherapy patients were comparable (69.1%; 95% CI, 58.2-77.7; and 70.4%; 95% CI, 58.5-79.4, respectively; P = 0.86). Conclusion: Radiotherapy has excellent local control and comparable overall survival in patients with well-compensated liver function, exhibiting advantageous characteristics and compensating for the deficiencies of other treatment modalities; radiotherapy appears to be an acceptable alternative treatment option for patients who are not candidates for RFA.
Radiofrequency ablation versus laparoscopic hepatectomy for hepatocellular carcinoma: A real world single center study.
Pan Yang-Xun,Long Qian,Yi Min-Jiang,Chen Jin-Bin,Chen Jian-Cong,Zhang Yao-Jun,Xu Li,Chen Min-Shan,Zhou Zhong-Guo
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
BACKGROUND:Both radiofrequency ablation (RFA) and laparoscopic hepatectomy (LH) are minimally invasive approach for hepatocellular carcinoma (HCC) at early stage. This study aimed to compare the efficacy of RFA and LH for treating HCC with a large cohort. METHODS:From March 2014 to July 2016, 477 patients who underwent RFA (n = 314) or LH (n = 163) for HCC tumors meeting the criteria were included. Overall survival (OS) and recurrence-free survival (RFS) were compared. Propensity score matching (PSM) was performed to balance for the factors that may affect the choice of treatment. RESULTS:Collectively, the 1-, 2- and 3-year OS rates were significantly greater after LH than RFA, as well the corresponding RFS rates, before and after PSM by 2:1. However, the RFA group had fewer major complications (P=0.004), shorter postoperative stays (P=0.023) and lower hospital charges (P<0.001) than the LH group. In the subgroup analysis, RFA demonstrated comparable RFS in treating less than 3 cm tumor (P=0.22) located in noncentral bisection (SII, SIII, SVI, SVII) and tumor between 3 cm and 5 cm (P=0.07) located in central bisections (SIV, SV, SVIII). The female, HBV infection, and RFA are factors of worse OS, and the latter two factors also indicated higher RFS. CONCLUSIONS:Though, LH possessed superior intrahepatic control rate than RFA in most condition of tumor smaller than 5 cm, the RFA could be an optimal approach achieved comparable outcomes in patients with centrally located HCC, with fewer major complications, shorter postoperative stays and lower hospital charges.
A novel nomogram to predict the local tumor progression after microwave ablation in patients with early-stage hepatocellular carcinoma: A tool in prediction of successful ablation.
An Chao,Wu Songsong,Huang Zhimei,Ni Jiayan,Zuo Mengxuan,Gu Yangkui,Zhang Tianqi,Huang Jinhua
OBJECTIVES:To develop a nomogram for the local tumor progression (LTP) in patients with early-stage hepatocellular carcinoma (HCC) after computed tomography-guided percutaneous microwave ablation (CT-PMWA) and to assess clinical-pathologic risk factors for individual LTP estimation. Furthermore, we compared the prognostic predictive ability for LTP between the nomogram and the traditional staging systems. METHODS:This retrospective study was approved by the institutional review board. Five hundred and forty treatment-naïve patients with HCC according to the Milan criteria, who subsequently underwent CT-PMWA were reviewed from 2009 to 2019. Baseline characteristics were collected to identify the risk factors for the determination of LTP after CT-PMWA. The multivariate Cox proportional-hazards model based on significant prognostic factors of LTP was used to construct the nomogram, which was then assessed for its predictive accuracy using mainly the Harrell's C-index and time-dependent area under the curve (tAUC). RESULTS:After a median follow-up time of 28.7 months, 6.5% (35/540) patients had LTP. The nomogram was developed based on the tumor size, tumor number, Child-Turcotte-Pugh (CTP) grade, platelet, and alanine aminotransferase (ALT). The nomogram had good calibration and discriminatory abilities in the training set, with C-indexes of 0.799 (95% confidence interval (CI): 0.738, 0.860), and tAUCs of 0.844 (CI: 0.728, 0.895), that were greater than those of traditional staging systems. Internal validation with 1000 bootstrap resamples had a good C-index of 0.735 (CI: 0.648, 0.816). CONCLUSIONS:The nomogram model can be used to predict accurately LTP after CT-PMWA for early-stage HCC, as well as to assist physicians during the therapeutic decision-making process.
The LI-RADS Version 2018 MRI Treatment Response Algorithm: Evaluation of Ablated Hepatocellular Carcinoma.
Chaudhry Mohammad,McGinty Katrina A,Mervak Benjamin,Lerebours Reginald,Li Cai,Shropshire Erin,Ronald James,Commander Leah,Hertel Johann,Luo Sheng,Bashir Mustafa R,Burke Lauren M B
Background The Liver Imaging Reporting and Data System LI-RADS) treatment response algorithm (TRA) is used to assess presumed hepatocellular carcinoma (HCC) after local-regional therapy, but its performance has not been extensively assessed. Purpose To assess the performance of LI-RADS version 2018 TRA in the evaluation of HCC after ablation. Materials and Methods In this retrospective study, patients who underwent ablation therapy for presumed HCC followed by liver transplantation between January 2011 and December 2015 at a single tertiary care center were identified. Lesions were categorized as completely (100%) or incompletely (≤99%) necrotic based on transplant histology. Three radiologists assessed pre- and posttreatment MRI findings using LI-RADS version 2018 and the TRA, respectively. Interreader agreement was assessed by using the Fleiss κ test. Performance characteristics for predicting necrosis category based on LI-RADS treatment response (LR-TR) category (viable or nonviable) were calculated by using generalized mixed-effects models to account for clustering by subject. Results A total of 36 patients (mean age, 58 years ± 5 [standard deviation]; 32 men) with 53 lesions was included. Interreader agreement for pretreatment LI-RADS category was 0.40 (95% confidence interval [CI]: 0.15, 0.67; < .01) and was lower than the interreader agreement for TRA category (κ = 0.71; 95% CI: 0.59, 0.84; < .01). After accounting for clustering by subject, sensitivity of tumor necrosis across readers ranged from 40% to 77%, and specificity ranged from 85% to 97% when LR-TR equivocal assessments were treated as nonviable. When LR-TR equivocal assessments were treated as viable, sensitivity of tumor necrosis across readers ranged from 81% to 87%, and specificity ranged from 81% to 85% across readers. Six (11%) of 53 treated lesions were LR-TR equivocal by consensus, with most (five of six) incompletely necrotic at histopathology. Conclusion The Liver Imaging Reporting and Data System treatment response algorithm can be used to predict viable or nonviable hepatocellular carcinoma after ablation. Most ablated lesions rated as treatment response equivocal were incompletely necrotic at histopathology. © RSNA, 2019 See also the editorial by Do and Mendiratta-Lala in this issue.
A comparison between radiofrequency ablation combined with transarterial chemoembolization and surgical resection in hepatic carcinoma: A meta-analysis.
Wang Hongye,Liu Yihai,Shen Kangjie,Dong Yuxiang,Sun Jinyu,Shu Yimei,Wan Xiaojie,Ren Xiaohan,Wei Xiyi,Zhai Bo
Journal of cancer research and therapeutics
Objective:This study determined whether the effect of combination therapy for hepatic carcinoma (HCC) is comparable to surgical resection (SR). According to the guidelines of the American Association for the Study of Liver Disease, radiofrequency ablation (RFA) and SR are recommended for early HCC. However, patients treated with RFA had worse long-term survival than those who received SR. Many studies utilizing the combination therapy with RFA and transarterial chemoembolization (TACE) have reported better prognosis as compared to RFA alone. Materials and Methods:A comprehensive search in databases was conducted. Six retrospective studies and one cohort were enrolled in this meta-analysis. The overall survival (OS), disease-free survival (DFS), and major complications were compared between RFA plus TACE and SR. The pooled hazard ratio and 95% confidence interval (CI) were calculated and analyzed. Results:After comparison, no significant difference in the OS and DFS at 1 and 3 years between the combination therapy and SR was observed (OS1: pooled relative risk [RR]: 0.82, 95% CI [0.56, 1.21]; OS3: pooled RR: 1.07, 95% CI [0.82, 1.39]; DFS1: pooled RR: 0.92, 95% CI [0.58, 1.45]; DFS3: pooled RR: 1.18, 95% CI [1.00, 1.40]). SR had better clinical outcomes than combination therapy with respect to long-term survival and disease progression (OS5: pooled RR: 1.12, 95% CI [1.03, 1.23]; DFS5: pooled RR: 1.15, 95% CI [1.03, 1.28]). Major complications were reduced with combination therapy (pooled RR: 0.46, 95% CI [0.25, 0.85]). Conclusion:SR should remain as the first-line therapy for early HCC.
Thermal ablation for hepatocellular carcinoma: what's new in 2019.
Zhu Feipeng,Rhim Hyunchul
Chinese clinical oncology
Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide, but a major proportion of patients are not appropriate candidates for surgical resection or transplantation. For this reason, image-guided tumor ablation using thermal energy for early-stage HCC has become an accepted curative treatment option in all HCC treatment guidelines due to its minimal invasiveness and proven outcomes. In recent years, microwave ablation (MWA) has been gaining popularity worldwide over radiofrequency ablation (RFA) due to its better performance with high temperature heating and lack of heat sink effects. However, more high-level evidence of real survival gain is required before MWA will completely replace RFA. Although cryoablation and irreversible electroporation are promising for safe and effective ablation in the liver, clinical evidence for these remains limited. In addition to specific ablative modalities, therapeutic outcomes can be improved by current technological advances in fusion imaging, contrast-enhanced ultrasound, and post-ablation antiviral therapy. In fact, immuno-ablation has the great potential to maximize therapeutic outcomes after ablation. The purpose of this review is to briefly illustrate the current status of ablation in HCC treatment guidelines and update on recently introduced therapeutic outcomes and new advances in ablation-related techniques.
Complications after Radiofrequency Ablation for Hepatocellular Carcinoma: A Multicenter Study Involving 9,411 Japanese Patients.
Maeda Masaki,Saeki Issei,Sakaida Isao,Aikata Hiroshi,Araki Yasuyuki,Ogawa Chikara,Kariyama Kazuya,Nouso Kazuhiro,Kitamoto Mikiya,Kobashi Haruhiko,Sato Shuichi,Shibata Hiroshi,Joko Kouji,Takaki Shintaro,Takabatake Hiroyuki,Tsutsui Akemi,Takaguchi Koichi,Tomonari Tetsu,Nakamura Shinichiro,Nagahara Takakazu,Hiraoka Atsushi,Matono Tomomitsu,Koda Masahiko,Mandai Mari,Mannami Tomohiko,Mitsuda Akeri,Moriya Takashi,Yabushita Kazuhisa,Tani Joji,Yagi Takahito,Yamasaki Takahiro
Introduction:Radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is considered a safe and minimally invasive procedure. We previously reported that the mortality and complication rates for RFA were 0.038% (5/13,283 patients) and 3.54% (579 complications/16,346 procedures), respectively, from 1999 to 2010 (previous period). In this study, we investigated the clinical criteria for RFA and the mortality and complication rates from 2011 to 2015 (recent period). Methods:Data were collected from 25 centers by using a questionnaire developed by the Chugoku-Shikoku Society for Local Ablation Therapy of HCC. The criteria for RFA, RFA modification, use of image-guidance modalities, mortality, and complications during the previous and recent periods were compared. Results:We evaluated 11,298 procedures for 9,411 patients, including those that involved new devices (bipolar RFA and internally adjustable electrode system). The criterion of hepatic function for RFA increased from a Child-Pugh score ≤8 during the previous period to ≤9 during the recent period. The criteria regarding the tumor location and other risk factors have been expanded recently because of the increased use of several modifications of the RFA procedure and image-guidance modalities. The mortality rate was 0.064% (6/9,411 patients), and the complication rate was 2.92% (330 complications/11,298 procedures). There was no difference in mortality rates between the 2 periods ( = 0.38), but the complication rates was significantly lower during the recent period ( = 0.038). Discussion and Conclusions:Our findings confirmed that RFA, including the use of new devices, is a low-risk procedure for HCC, despite the expansion of the criteria for RFA during the recent period.
MRI-guided stereotactic radiation therapy for hepatocellular carcinoma: a feasible and safe innovative treatment approach.
Boldrini Luca,Romano Angela,Mariani Silvia,Cusumano Davide,Catucci Francesco,Placidi Lorenzo,Mattiucci Gian Carlo,Chiloiro Giuditta,Cellini Francesco,Gambacorta Maria Antonietta,Indovina Luca,Valentini Vincenzo
Journal of cancer research and clinical oncology
PURPOSE:Hepatocellular carcinoma (HCC) in early stages benefits from local ablative treatments such as radiofrequency ablation (RFA) or transarterial chemoembolization (TACE). In this context, radiotherapy (RT) has shown promising results but has not been thoroughly evaluated. Magnetic resonance-guided RT (MRgRT) may represent a paradigm shifting improvement in stereotactic body radiotherapy (SBRT) for liver tumors. METHODS:We retrospectively evaluated HCC patients treated on a hybrid low-tesla MRgRT unit. A total biologically effective dose (BED) > 100 Gy was delivered in 5 consecutive fractions, respecting the appropriate organs-at-risk constraints. Hybrid MR scans were used for treatment planning and cine MR was used for delivery gating. Patients were followed up for toxicity and treatment-response assessment. RESULTS:Ten patients were enrolled, with a total of 12 lesions. All the lesions were irradiated with no interruptions. Six patients had already performed previous local therapies. Median follow-up after SBRT was 6.5 months (1-25). Two cases of acute toxicity were reported (G ≤ 2 according to CTCAE v4.0). At the time of the analysis, 90% of the population presented local control. Child-Pugh before and after treatment remained unchanged in all but one patient. CONCLUSION:MRgRT is a feasible and safe option showing favorable toxicity profile for HCC treatment.
Small single perivascular hepatocellular carcinoma: comparisons of radiofrequency ablation and microwave ablation by using propensity score analysis.
An Chao,Li Wang-Zhong,Huang Zhi-Mei,Yu Xiao-Ling,Han Yu-Zhi,Liu Fang-Yi,Wu Song-Song,Yu Jie,Liang Ping,Huang Jinhua
OBJECTIVES:We aimed to compare the therapeutic outcomes of radiofrequency ablation (RFA) and microwave ablation (MWA) as first-line therapies in patients with small single perivascular hepatocellular carcinoma (HCC). METHODS:A total of 144 eligible patients with small (≤ 3 cm) single perivascular (proximity to hepatic and portal veins) HCC who underwent RFA (N = 70) or MWA (N = 74) as first-line treatment were included. The overall survival (OS), disease-free survival (DFS), and local tumor progression (LTP) rates between the two ablation modalities were compared. The inverse probability of treatment weighting (IPTW) method was used to reduce selection bias. Subgroup analysis was performed according to the type of hepatic vessels. RESULTS:After a median follow-up time of 38.2 months, there were no significant differences in OS (5-year OS: RFA 77.7% vs. MWA 74.6%; p = 0.600) and DFS (5-year DFS: RFA 24.7% vs. MWA 40.4%; p = 0.570). However, a significantly higher LTP rate was observed in the RFA group than the MWA group (5-year LTP: RFA 24.3% vs. MWA 8.4%; p = 0.030). IPTW-adjusted analyses revealed similar results. The treatment modality (RFA vs. MWA: HR 7.861, 95% CI 1.642-37.635, p = 0.010) was an independent prognostic factor for LTP. We observed a significant interaction effect of ablation modality and type of peritumoral vessel on LTP (p = 0.034). For patients with periportal HCC, the LTP rate was significantly higher in the RFA group than in the MWA group (p = 0.045). However, this difference was not observed in patients with perivenous HCC (p = 0.116). CONCLUSIONS:In patients with a small single periportal HCC, MWA exhibited better tumor control than RFA. KEY POINTS:• Microwave ablation exhibited better local tumor control than radiofrequency ablation for small single periportal hepatocellular carcinoma. • There was a significant interaction between the treatment effect of ablation modality and type of peritumoral vessel on local tumor progression. • The type of peritumoral vessel is vital in choosing ablation modalities for hepatocellular carcinoma.
Comparison of radiofrequency ablation and surgical resection for hepatocellular carcinoma conforming to the Milan criteria: a meta-analysis.
Wang Qiang,Tang Maocai,Zhang Shouru
ANZ journal of surgery
BACKGROUND:The purpose of this study was to include all current randomized controlled trials to compare the clinical efficacy between radiofrequency ablation (RFA) and surgical resection (SR) in patients with hepatocellular carcinoma who meet the Milan criteria using meta-analysis techniques. METHODS:We conducted literature search of PubMed, Embase and Cochrane library clinical database for studies of RFA versus SR. Only randomized clinical trials were included. The odds ratios (OR) were pooled and calculated with 95% confidence intervals (CIs) for both fixed-effects and random-effects models. RESULTS:A total of 8 randomized controlled trials with 1177 patients were included in the present meta-analysis. There were no significantly difference between the patients underwent SR or RFA in terms of 1, 3 and 5 years' overall survival rate (OR 0.87, 95% CI 0.46-1.64; OR 0.84, 95% CI 0.57-1.24 and OR 1.03, 95% CI 0.61-1.73, respectively). And there were no significantly difference between the patients received SR and RFA in terms of 1 and 3 years' disease-free survival rate (OR 0.85, 95% CI 0.61-1.18 and OR 0.77, 95% CI 0.57-1.03). However, it is worth noting that RFA has advantages over SR in terms of treatment-related complications (OR 0.65, 95% CI 0.44-0.80; P < 0.05), post-operative mortality, length of stay and hospitalization costs. CONCLUSION:For patients with hepatocellular carcinoma who meet the Milan criteria, RFA exhibited similar clinical efficacy to SR.
Treatment effect of radiofrequency ablation versus liver transplantation and surgical resection for hepatocellular carcinoma within Milan criteria: a population-based study.
Zhuang Bo-Wen,Li Wei,Wang Wei,Li Bin,Lu Ming-de,Kuang Ming,Xie Xiao-Hua,Xie Xiao-Yan
OBJECTIVES:Restricted mean survival time (RMST) has been increasingly used to assess the treatment effect. We aimed to evaluate a treatment effect of radiofrequency ablation (RFA) versus liver transplantation (LT) and surgical resection (SR) for hepatocellular carcinoma (HCC) within Milan criteria by using an adjusted RMST. METHODS:A total of 7,218 HCC patients (RFA, 3,327; LT, 2,332; SR 1,523) within Milan criteria were eligible for this retrospectively study. The RMST using inverse probability of treatment weighting (IPTW) adjustment were applied to estimate the treatment effect between RFA and LT, RFA, and SR groups. RESULTS:The 3-, 5-, and 10-year IPTW-adjusted difference in RMST of OS for LT over RFA were + 4.5, + 12.4, and + 36.3 months, respectively. For SR versus RFA group, the survival benefit was + 2.3, + 6.1, and + 15.8 months at 3, 5, and 10 years, respectively. But the incremental survival benefit of SR over RFA was only half than that of LT over RFA. In the subgroup of solitary tumor ≤ 2 cm, the adjusted RMST of RFA versus SR was comparable with no statistical differences. Beyond that, in comparison with RFA, a notably greater efficacy of LT and SR was consistently across all subgroups with solitary HCC > 2.0 cm, AFP positive or negative, and fibrosis score 0-4 or 5-6. CONCLUSIONS:RMST provides a measure of absolute survival benefit at a specific time point. Using IPTW-adjusted RMST, we showed that the incremental survival benefit of SR over RFA was about half than that of LT over RFA. KEY POINTS:• The restricted mean survival time offers an intuitive, clinically meaningful interpretation to quantify the treatment effect than the hazard ratio. • Liver transplantation and surgical resection provided better overall survival compared to radiofrequency ablation for HCC patients within Milan criteria, but RFA and SR provide equivalent long-term overall survival for solitary HCC ≤ 2 cm. • The incremental survival benefit of surgical resection over radiofrequency ablation was only half than that of liver transplantation over radiofrequency ablation.
Efficacy and safety of radiofrequency ablation versus laparoscopic hepatectomy for small hepatocellular carcinoma: A protocol for a randomized controlled trial.
Zhu Fuping,Chang Qing,Duan Shigang,Leng Weiye
BACKGROUND:Hepatocellular carcinoma (HCC) is one of the most common type of malignant tumors in adults, and is the most common cause of death in people with cirrhosis. Both laparoscopic hepatectomy (LH) and radiofrequency ablation (RFA) are radical treatments for small HCC. However, there is no international standard for the treatment of small HCC, and it is still controversial to choose LH or RFA in treating small HCC. We try to carry out a randomized, controlled, prospective study to compare the the short-term and long-term effects and safety of LH versus RFA in the treatment of small HCC. METHODS:This study is a single-center, evaluator-blinded, randomized, controlled clinical trial (RCT). The patients will be randomly divided into RFA group and LH group in a 1:1 ratio according to a computer-generated randomization list. Postoperative complications rates, Alpha fetoprotein (AFP), hospital stay, 1, 2, 3-year overall survival (OS) rates, disease-free survival (DFS) rates and all possible adverse events will be recorded. Statistical analyses will be performed with SPSS v22.0 software. CONCLUSIONS:The study will compare the the short-term and long-term effects and safety of LH versus RFA in the treatment of small HCC. OSF REGISTRATION NUMBER:doi: 10.17605/OSF.IO/HNX2T.
Overall survival and local recurrence following RFA, MWA, and cryoablation of very early and early HCC: a systematic review and Bayesian network meta-analysis.
Gupta Pankaj,Maralakunte Muniraju,Kumar-M Praveen,Chandel Karamvir,Chaluvashetty Sreedhara B,Bhujade Harish,Kalra Naveen,Sandhu Manavjit Singh
OBJECTIVE:To compare overall survival (OS) and local recurrence (LR) following radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation (CA) for very early and early hepatocellular carcinoma (HCC). METHODS:This systematic review was performed according to the PRISMA guidelines. MEDLINE, Embase, and Cochrane databases were searched. Randomized controlled trials (RCTs) and observational studies were included. OS and LR at 1 year and 3 years were assessed. OS was reported as hazard ratio (HR) with 95% credible intervals (CrI) and LR as relative risk (RR) with 95% CrI, to summarize effect of each comparison. RESULTS:Nineteen studies (3043 patients), including six RCTs and 13 observational studies, met inclusion criteria. For OS at 1 year, as compared to RFA, CA had HR of 0.81 (95% CrI: 0.43-1.51), and MWA had HR of 1.01 (95% CrI: 0.71-1.43). For OS at 3 years, as compared to RFA, CA had HR of 0.90 (95% CrI: 0.48-1.64) and MWA had HR of 1.07 (95% CrI: 0.73-1.50). For LR at 1 year, CA and MWA had RR of 0.75 (95% CrI: 0.45-1.24) and 0.93 (95% CrI: 0.78-1.14), respectively, as compared to RFA. For LR at 3 years, CA and MWA had RR of 0.96 (0.74-1.23) and 0.98 (0.87-1.09), respectively, as compared to RFA. Overall, none of the comparisons was statistically significant. Age of patients and tumor size did not influence treatment effect. CONCLUSIONS:RFA, MWA, and CA are equally effective for locoregional treatment of very early and early HCC. KEY POINTS:• There is no significant difference in the OS and LR (at 1 year and 3 years) following ablation of very early and early HCC with RFA, MWA, and CA. • There was no effect of tumor size on the treatment efficacy. • More RCTs comparing CA with RFA and MWA should be performed.
Extrapolating Prognostic Factors of Primary Curative Resection to Postresection Recurrences Hepatocellular Carcinoma Treatable by Radiofrequency Ablation.
Ma Hui,Li Zhongchen,Yuan Jia,Zhang Lan,Xie Xiaoying,Yin Xin,Chen Rongxin,Ren Zhenggang
Gastroenterology research and practice
Objective:Recurrence after curative resection for hepatocellular carcinoma (HCC) is a major cause of death from this disease. Factors of primary curative resection are available and potential in the prognosis of follow-up treatment. Our aim was to assess the prognostic significance of primary curative resection factors in recurrent HCC patients undergoing radiofrequency ablation therapy (RFA). Methods:In this retrospective study, we assessed 235 patients who underwent limited RFA of HCC recurrences (tumors ≤ 5 cm; nodules ≤ 3) after primary curative resection. Factors of primary curative resection were collected, and overall survival and recurrence-free survival were evaluated by the Kaplan-Meier method. Univariate and multivariate analyses were used to identify significant prognostic factors. Results:After a median follow-up of 36 months, 54 patients died, and 128 patients had hepatic recurrence. On univariate analyses, patients whose primary tumors were less differentiated ( = 0.032 and = 0.048) and required less time to recur ( = 0.013 and = 0.001) after curative resection displayed poorer overall survival and higher recurrence rates following RFA. On multivariate analyses, the pathologic tumor grade ( = 0.026 and = 0.038) and recurrence-free survival after primary curative resection ( = 0.028 and < 0.001) emerged as independent risk factors of survival and HCC recurrence. Conclusions:Primary tumor differentiation and time to recurrence after curative resection are viable prognostic factors of overall survival and further recurrence risk in patients undergoing RFA of recurrent HCC.