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Objectives: Comparison of the therapeutic efficacy of percutaneous microwave ablation (MWA) and radio frequency ablation (RFA) for treatment of hepatocellular carcinomas (HCC). Subjects and method: 136 patients with HCC were divided into two groups. 66 patients with 71 tumors were treated with MWA and 70 with 74 tumors were treated with RFA.
Journal of military pharmaco-medicine no2-2018 COMPARISON OF THE THERAPEUTIC EFFICACY OF MICROWAVE ABLATION AND RADIO-FREQUENCY ABLATION FOR HEPATOCCELULAR CARCINOMAS Vo Hoi Trung Truc*; Tran Viet Tu** SUMMARY Objectives: Comparison of the therapeutic efficacy of percutaneous microwave ablation (MWA) and radio frequency ablation (RFA) for treatment of hepatocellular carcinomas (HCC) Subjects and method: 136 patients with HCC were divided into two groups 66 patients with 71 tumors were treated with MWA and 70 with 74 tumors were treated with RFA Results: The complete response rate of MWA and RFA were 95.7% and 97.3%, respectively No significant differences in the complete response rate between modalities (MWA and RFA) and tumor sizes (< cm and ≥ cm) The disease-free survival (DFS) rates at and years in the MWA group were 68.2% and 43.9% with a mean DFS period of 17.4 ± 9.2 months Those at and years in the RFA group were 65.7% and 41.4%, respectively with a mean DFS period of 16.8 ± 8.7 months No significant difference in the DFS rates (p = 0.76 and 0.767) and DFS period (p = 0.446) between groups Platelet, age and AFP were identified independent prognostic factors for DFS by using Cox’s proportional hazards model Conclusion: MWA has the similar efficacy to RFA in treating HCCs Platelet, age and AFP were prognostic factors for DFS * Keywords: Hepatocellular carcinoma; Microwave ablation; Radio frequency ablation INTRODUCTION Liver cancer in men is the fifth most frequently diagnosed cancer worldwide but the second most frequent cause of cancer death In women, it is the seventh most commonly cancer and the sixth leading cause of cancer death [3] Local ablation therapies have been recognized as radical, minimally invasive ones for early HCCs Among a variety of these, RFA is the most common thermal ablation modality worldwide MWA was first deployed in Choray Hospital in June 2012 and should be proven its efficacy in destroying liver tumors in Vietnam Therefore, we did this research in order to: Compare the local ablation effects of percutaneous MWA and RFA in the treatment of HCC SUBJECTS AND METHODS Subjects 136 patients were diagnosed with HCCs and treated in the Liver Tumor Department, Choray Hospital between June, 2012 and December, 2013 They were divided into two groups: MWA group (66 patients with 71 tumors) and RFA group (70 patients with 74 tumors) * Choray Hospital ** 103 Military Hospital Corresponding author: Vo Hoi Trung Truc (bstruc200667@gmail.com) Date received: 20/11/2017 Date accepted: 22/01/2018 134 Journal of military pharmaco-medicine no2-2018 * Inclusion criteria: The pathological enhancement within the ablation area or finding is HCC, liver tumors (one or two the target tumor [1] All patients with nodules of cm or smaller in size), Child- incomplete ablation were further treated Pugh A or B, prothrombin time more than by complementary ablations All patients 50% were regularly followed up every - and platelet count more than 50.000/mm , unresectable HCC or patients’ refusal to undergo surgery, patients agree to participate in the study months during the follow-up Continuous variables were reported as mean ± standard deviation Differences in * Exclusion criteria: Patients with PST categorical variables and continuous > 2, venous thrombosis (portal vein, hepatic variables vein, lower vena cava), bile duct dilation, analyzed with the Chi-square test or distant metastasis or invasion of adjacent Fisher’s exact test and with student’s organs t-test, between respectively, groups using Stata version A total of 136 eligible patients were signed-rank test is used when comparing enrolled in this prospective cohort study two matched samples DFS curve was Under the guidance of real-time ultrasound, evaluated using Kaplan-Meier curve and the antenna of the microwave system compared using the log-rank test To AveCure (Medwaves, USA) or the electrode identify the prognostic factors for DFS, 12 of Valley-lab Cool-tip™ RF Ablation System variables were used, including ablation (Covidien, USA) was percutaneously probed modality (MWA/RFA), age (< 60, ≥ 60), into the tumors A RFA was applied for - sex (male, female), albumin (< 3.5; ≥ 3.5 12 mins and a MWA for 7.5 - 10 mins until mg%), bilirubine (< 2, ≥ mg%), platelet whole tumor was ablated completely with (< 100, ≥ 100), prothrombin time (< 16, a safety margin of - 10 mm Patients ≥ 16), AFP level (< 200, ≥ 200), tumor were discharged one day after procedures differentiation (1, 2, 3), tumor size (< 3, A was ≥ cm), tumor number (1, 2), BCLC (0, A, performed month after ablation The B) Variables with p values less than 0.05 local efficacy was evaluated Complete in the univariate analysis were entered ablation was defined as that the ablated into a Cox proportional hazards model for area completely covers the target tumor multivariate analysis A p-value less than Incomplete ablation was defined as any 0.05 was considered statistically significant CT-scan software the were Methods contrast-enhanced 13.0 the The Wilcoxon 135 Journal of military pharmaco-medicine no2-2018 RESULTS Patients’ baseline characteristics Table 1: Characteristics of patients MWA group (n1 = 66) RFA group (n1 = 70) p Sex Male/female 55/11 62/8 0.379 Age Mean ± SD 60.8 ± 10.9 62.1 ± 10.7 0.408 Platelet (G/L) Mean ± SD 154.3 ± 68.5 172.2 ± 68.1 0.129 Fibrinogen (g/L) Mean ± SD 2.8 ± 1.3 2.8 ± 0.7 0.958 Prothrombin time (sec) Mean ± SD 13.8 ± 2.2 14.2 ± 1.8 0.312 APTT (sec) Mean ± SD 31.5 ± 4.3 31.9 ± 5.1 0.615 AST(U/L) Median (IQR) 61 (46 - 94) 60(45 - 87) 0.459 ALT(U/L) Median (IQR) 48 (37 - 88) 45(28 - 70) 0.729 Bilirubine (mg/dL) Median (IQR) 0.9 (0.6 - 1.2) 0.8(0.6 - 1.1) 0.221 Albumin blood (g/dL) Mean ± SD 4.2 ± 0.6 4.2 ± 0.5 0.629 Tumor differentiation 1/2/3 21/44/1 20/49/1 0.854 A/B 60/6 63/7 1.00 0/A/B 3/59/4 5/63/2 0.579 PST 0/1 62/4 66/4 1.00 The number of nodules 1/2 61/5 66/4 0.739 Median follow-up time Median (IQR) 24.7 (14 - 25.7) 24.4 (15.7 - 25.4) 0.806 Child-Pugh BCLC (n1: Total number of patients) There was no significant difference in clinical backgrounds between the two groups Ablation effectiveness Table 2: AFP changing after treatments AFP level MWA group (n1 = 66) RFA group (n1 = 70) Before the procedure Median (IQR) 11.8 (6.0 - 39.7) 11.2 (5.8 - 28.9) After the procedure Median (IQR) 7.5 (4.6 - 19.4) 8,1 (3.6 - 13.3) < 0.001 < 0.001 p AFP levels after treatment decreased significantly in both two groups 136 Journal of military pharmaco-medicine no2-2018 Table 3: Technique effectiveness MWA group (n2 = 71) p RFA group (n2 = 74) < 2/2 - 3/>3 3/27/41 0.534 5/33/36 Mean ± SD 3.3 ± 0.573 3.2 ± 1/≥ 57/14 0.504 56/18 Mean ± SD 1.2 ± 0,4 0.220 1.3 ± 0.6 Nodule size (cm) Sessions for one nodule Complete response Overall 95.8% 97.3% Nodule ≤ cm 97% 97.5% Nodule > cm 94.6% 97.1% (n2: Total number of nodules) No significant differences in nodule sizes and the number of ablation sessions for the target nodule were observed between the MWA and the RFA groups The CA rate in the tumor treated with MWA was the same as one in the tumors treated with RFA Disease free survival Table 4: DFS and rate MWA group (n1 = 66) RFA group (n1 = 70) p Disease free 1-year survival 68.2% 65.7% 0.76 Disease free 2-year survival 43.9% 41.4% 0.767 17.4 ± 9.2 (months) 16,8 ± 8.7 (months) 0.724 Mean DFS No significant differences in the DFS rates and DFS period between two groups Prognostic factors Table 5: Prognostic factors of complete response Multiple linear regression Odds ratio p-value 95%CI Ablation modality (MWA/RFA) 1.5 0.64 0.2 9.6 Nodule size (≤ cm, > cm) 0.6 0.64 0.1 No significant differences in the complete response rate between modalities (MWA and RFA) and tumor sizes (< cm and ≥ cm) 137 Journal of military pharmaco-medicine no2-2018 Table 6: Prognostic factors of DFS Multivariate analysis Hazard ratio p-value 95%CI Age(< 60, ≥ 60) 0,6 0.021 0,4 0,9 Platelet (< 100, ≥ 100) 0.4 0.002 0.2 0.7 AFP level (< 200, ≥ 200) 1.5 0.013 1.1 1.9 Variables were analyzed: ablation modality (MWA/RFA), sex (male, female), age (< 60, ≥ 60), albumin (≤ 3.5; > 3.5 mg%), bilirubine (≤ 2, > cm), platelet (< 100, ≥ 100), prothrombin time (< 16, ≥ 16), AFP level (< 200, ≥ 200), tumor differentiation (1, 2, 3), nodule size (< 3, ≥ cm), nodule number (1, 2), BCLC (0, A, B) Age, platelet count and AFP were independent prognostic factors of DFS DISCUSSION There was no significant difference in clinical backgrounds between the two groups AFP levels after treatment decreased significantly in both two groups Technique effectiveness of MWA Complete response confirmed at month after treatment is very important It is one of the main criteria to evaluate the efficacy of ablation The complete response rate of MWA group was 95.8% This rate is not different from many other studies Liu et al realized that 85.7% of tumors in the 915 MHz MW group and 73.7% of tumors in the 2,450 MHz MW group achieved complete ablation [4] Xu et al found that the complete response was 94.6% In our study, there was no difference between the complete response rate in nodules ≤ cm and the one in nodules > cm (p = 0.64) [7] Hetta et al showed that MW ablation success was higher with nodules ≤ cm (98.3%) in comparison to nodules > cm (92.5%) However, the 138 difference was not significant (p = 0.301) [2] Lu et al documented the complete response rate achieved using MWA group was 94.9% Complete response rates were 98.6% in tumors ≤ cm versus 83.3% in tumors > cm (p = 0.01) [8] Wang et al found that patients with tumor > cm were less likely to gain complete ablation at first microwave ablation and more likely to suffer from incomplete ablation after two sessions of MWA compared with those with tumor ≤ cm However, tumor number and location have no significant impact on technique effectiveness [6] The therapeutic efficacy of MWA versus RFA Theoretically, MWA outperforms RFA in some areas, such as faster ablation time, bigger coagulation volume, higher tumor temperature and being less affected by the heat-sink effect of local blood vessels However, we found that the CR rates using MWA and RFA were 95.8% and 97.3%, respectively There was no difference Journal of military pharmaco-medicine no2-2018 between the two groups (p = 0.64) Lu et al found that the complete response rates were 94.9% using MWA versus 93.1% using RFA (p = 0.75) [8] Zhang et al reported the complete response rate was achieved in 86.7% of tumors treated with MWA and 83.4% of the treated those with RFA, with no significant difference between the two groups (p = 0.957) [9] Xu et al found that the complete response rate in MW and RF ablation was 94.6% and 89.7%, respectively (p > 0.05) [7] Disease free survival According to our study, the 1-year and 2-year DFS rates in the MWA group were 68.2% and 43.9%, respectively with a mean DFS period of 17.4 ± 9.2 months The 1-year and 2-year DFS rates in the RFA group were 65.7% and 41.4% with a mean DFS period of 16.8 ± 8.7 months There was no difference in disease free 1year survival (0.76), disease free 2-year survival (p = 0.767) and mean DFS period (p = 0.724) between the two groups The outcome in our study is better than that in the Lu et al’s study Lu et al showed that the DFS rates at 1, 2, years in the MWA group were 45.9%, 26.9%, 26.9%, respectively, with a mean DFS period of 15.5 months The DFS rates at 1, 2, years in the RFA group were 37.2%, 20.7%, 15.5%, respectively, with a mean DFS period of 16.5 months (p = 0.53) in comparison with the MWA group [8] Zhang et al showed that the 1-, 3-, 5-year DFS rates were 62.3%, 33.8%, 20.8%, respectively, for the MWA group and 70.5%, 42.3%, 34.2%, respectively for the RF ablation group There was no significant difference between these two groups (p = 0.123) [9] Vogl et al reported that the progression-free survival rate at and years were much higher than ours In the Vogl et al’s study, the progressionfree survival rate for patients treated with MWA of 1, 2, years were 97.2%, 94.5%, 91.7 and treated with RFA were 96.9%, 93.8%, and 90.6%, respectively (p = 0.98) [5] The difference was not significant between the two groups (p = 0.98) [5] We confirmed that the prognostic factors of DFS were age (< 60, ≥ 60), platelet (< 100, ≥ 100) and AFP level (< 200, ≥ 200) Wang et al identified levels of AFP and GGT as independent prognostic factors of recurrence-free survival in patients receiving MWA [6] 139 Journal of military pharmaco-medicine no2-2018 CONCLUSION Findings in this study revealed that the complete response rates of MWA and RFA were 95.8% and 97.9%, respectively There was no difference between the two groups (p = 0.64) There was no difference between the complete response rate in nodules ≤ cm and the one in nodules > cm (p = 0.64) The 1-year and 2-year DFS rates in the MWA group were 68.2% and 43.9% with a mean DFS period of 17.4 ± 9.2 months The 1-year and 2-year DFS rates in the RFA group were 65.7% and 41.4% with a mean DFS period of 16.8 ± 8.7 months There was no difference in disease free 1-year survival (0.76), disease free 2-year survival (p = 0.767) We confirmed that age (< 60, ≥ 60), platelet (< 100, ≥ 100) and AFP level (< 200, ≥ 200) were the prognostic factors of DFS after ablations REFERANCES Goldberg S.N, Charboneau J.W, D.G r, Dupuy D.E, Gervais D.A, Gillams A.R, Kane 140 R.A, Lee F.T Jr, Livraghi T, McGahan J.P, Rhim H, Silverman S.G Image-guided tumor ablation: Proposal for atandardization of terms and reporting criteria Radiology 2003, 228 (2), pp.335-345 Hetta O.M, Shebrya N.H, Amin S.K Ultrasound-guided microwave ablation of hepatocellular carcinoma: Initial institutional experience The Egyptian Journal of Radiology and Nuclear Medicine 2011, 42 (3-4), pp 343-349 Jemal A, Bray F., Center M.M et al Global cancer statistics CA: a Cancer Journal for Clinicians 2011, 61 (2), pp.69-90 Liu F.Y, Yu X.L, Liang P et al Comparison of percutaneous 915 MHz microwave ablation and 2,450 MHz microwave 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microwave ablation for hepatocellular carcinoma PLoS One 2013, (10), p.e76119 141 ... percutaneous thermal ablation of hepatocellular carcinoma using microwave and radiofrequency ablation Clinical Radiology 2003, 59 (1), pp.53-61 Zhang L, Wang N, Shen Q et al Therapeutic efficacy of percutaneous... number of ablation sessions for the target nodule were observed between the MWA and the RFA groups The CA rate in the tumor treated with MWA was the same as one in the tumors treated with RFA... effectiveness of MWA Complete response confirmed at month after treatment is very important It is one of the main criteria to evaluate the efficacy of ablation The complete response rate of MWA group