Evaluation of the short - Term outcome of radiofrequency ablation in hepatocellular carcinoma treatment at Binh Dan hospital

T¹p chÝ y - d−îc häc qu©n sù sè 8-2020 177 EVALUATION OF THE SHORT-TERM OUTCOME OF RADIOFREQUENCY ABLATION IN HEPATOCELLULAR CARCINOMA TREATMENT AT BINH DAN HOSPITAL Ngo Viet Thi1, Pham Vinh Quang1 SUMMARY Objectives: To evaluate technical success as complete ablation rate, tumor progression, the safety and short-term outcome of radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC) treatment. Subjects and methods: Case series with 30 patients treated with RFA from 6/2014 - 6/2017 at Binh Dan Hospital. Results: RFA was perfomed percutaneously in 30 patients with complete ablation rate was 90%, recurrence rate at 3, 6 and 12 months followed up was 0%, 23.33% and 30%, respectively. Only one case (3.3%) with minor complication and no treatment-related deaths was recorded. Conclusions: RFA is an effective and safe treatment for small or unresectable HCC. However, further controlled trials are needed to determine the effect of hepatic RFA on long-term survival. * Keywords: Hepatocellular carcinoma; Radiofrequency ablation; Therapy, Survival; Efficacy. INTRODUCTION Hepatocellular carcinoma is a very common disease in both genders. The risk of HCC is surprisingly high in chronic hepatitis B, C or cirrhosis. Surveillance programs addressed to the early detection of small nodular type HCC in patients with chronic liver diseases are increasing the eligibility for local or surgical treatments. Nowadays, curative treatment for HCC includes liver resection, liver transplant and local therapy. However, in Vietnam, liver transplant still get many challenges due to the lack of donor organs. Liver resection brings good results but only 10 - 25% of patients are eligible to surgery because of problems such as multi focal tumor, not enough functional liver remnant... So, the local therapy (especially RFA) is strongly focused nowadays to give a better outcome for the patients. At present, RFA is the best indication for small HCC (≤ 3 cm) with no more than 3 lesions or unresectable tumor or in HCC patients who refused to undergo liver resection with promising outcome. The advantages of RFA is the high capacity of complete tumor destruction, it is a less invasive therapy which help to conserve the functional liver remnant with minor complications. However, although RFA was utilized throughout the world, it was not frequently applicated at Binh Dan Hospital and its efficacy is still on debate. Thus, we carried out this study: To investigate the efficacy and the safety of RFA in HCC. 1Binh Dan Hospital, Ho Chi Minh City Corresponding author: Ngo Viet Thi (ngovietthi@yahoo.com) Date received: 01/9/2020 Date accepted: 07/10/2020 T¹p chÝ y - d−îc häc qu©n sù sè 8-2020 178 SUBJECTS AND METHODS 1. Subjects 30 patients diagnosed with HCC were treated with RFA at Binh Dan Hospital from 6/2014 - 6/2017. * Inclusion criteria: Diagnosis of HCC was confirmed by specific wash-out image on multi-slice computed tomography or by core biopsy. The patients were indicated for RFA based on AASLD guidelines for HCC or patient with resectable lesion but refused to undergo surgery. * Exclusion criteria: Absolute exclusion criteria were 4 or more lesions, tumor diameter is more than 3 cm, portal thrombosis or progressive lesion which invade portal or hepatic vein, while relative contraindication for ablation is lesion located closely to important organs and serious coagulopathy (platelet counts less than 50,000 per mm3 or PT < 50%). 2. Methods * Patients and HCC characteristics: From 6/2014 - 6/2017, 30 consecutive patients fulfilling the inclusion criteria were treated with RFA. Pretreatment assessment was performed before each treatment with ordinary liver function tests, prothrombin time and alpha-foetoprotein (AFP), platelet counts, chest X-ray, abdominal ultrasound and abdominal multi-sliced computed tomography scan. The procedures were all performed percutaneously with ultrasound guidance. The patient was followed and discharged from hospital the following day if no complication was noticed. The surveillance protocol included early treatment response assessment by contrast-enhanced CT scan performed 1 month after the first treatment, and a long-term response evaluation with alphafoetoprotein measurement, abdominal ultrasound every 3 months with chest/abdominal CT scan in case of suspicion of recurrence or distal metastasis. The aim of this monitoring was to detect signs of both local tumor progression and new lesions separated from the previously treated nodule. Complete ablation was defined as no enhancements in both peripheral or intra-nodular on arterial phase at ablative site on the 1-month CT scan. Multicentric disease was defined as onset of more than 3 nodules or portal thrombosis or extrahepatic disease. An intra-nodular/peripheral enhancement at CT scan after the first treatment was considered incomplete ablative and if the patient still met the inclusion criteria, RFA was repeated. An intra-nodular/peripheral enhancement at CT scan after the lesion was completely treated (no enhancements after the first ablation at the first month CT scan was accounted as local recurrence). New lesions, or distant intrahepatic recurrence, was defined as new lesion appeared in the liver separate from the ablated area. Extrahepatic metastasis refers to any tumor recurrence out-side the liver. * Data analysis: Continuous data were expressed as the median and the range. Groups were compared by using Chi-square test. All statical analysis were performed by using Stata MP for Windous statical package. A p-value less than 0.05 was considered to indicate statistical significance. T¹p chÝ y - d−îc häc qu©n sù sè 8-2020 179 RESULTS Table 1: General characteristics of patients. Characteristics n (%) Sex, males 25 (83.0) Age 60.9 8.9 HBV 10 (33.0) HCV 14 (46.0) Ethanol abused 2 (4.0) Etiology Others 4 (13.0) AFP 185.2 ng/mL (2 - 2,000 ng/mL) 1 tumor 27 (90.0) 2 tumors 3 (10.0) Total numbers of tumors 3 tumors 0 (0.0) Size of tumor 2.27 ± 0.589 cm Follow-up observation time was 12 months for all the patients. During the observation time, there were 30 patients with 33 HCC lesions who were treated with RFA at Hepatology Department, Binh Dan Hospital. On patient-basis, a complete “tumor” response rate (complete ablation rate -complete response rate) was 90% (27/30 patients). On nodular-basis, the complete response rate was 90.9% (30/33 lesions). All 3 patients with incomplete ablative tumor were going for secondary ablation and complete tumor destruction was archived in all three based on CT scan one month later. Table 2: Recurrence rate after RFA. Within the observation time, the recurrence rate at 3, 6 and 12 months were 0%, 23.33% and 30%, respectively. At 6 months, there were 7 patients with signs of recurrence disease (4 local recurrence and 3 new lesions). They were checked both clinically and paraclinically and no signs of distal metastasis were noted, their liver function was still acceptable so they were all going for additional ablation. 3 months 6 months 12 months Recurrence n (%) Local recurrence 0 (0.0) 4 (13.33) 4 (13.33) Distant intrahepatic recurrence 0 (0.0) 3 (10.0) 5 (16.66) Extrahepatic metastasis 0 (0.0) 0 (0.0) 0 (0.0) T¹p chÝ y - d−îc häc qu©n sù sè 8-2020 180 * Complications after RFA: During the observation period, there was no treatment-related deaths, no major complications which require surgery, only one case (4.4%) with minor complication. The patient developed punction-site abscess 1 week after the first RFA treatment and was treated with percutaneous drainage with antibiotics. Then this patient could later move well and was discharged from hospital the following day. DISCUSSION Nowadays, liver resection is still the best treatment method for HCC in both overall survival rate and recurrence rate. However, despite the good outcome, hepatectomy carries lot of risks with high mortality rate and complications, thus HCC usually develops on liver with severe cirrhosis which made the conservation of the normal liver tissue a big problem. Luckily, RFA is a good alternative choice to treat HCC with its good result being accepted worldwide. Moreover, RFA is a less invasive therapy and can be repeated easily to treat recurrent cases. Data strongly support RFA as an effective treatment for single HCC ≤ 2 cm even when surgical resection is possible [1, 8]. As recently report for RFA less than 3.5 cm in size, the technical efficacy (complete tumor ablation) ranges from 76 - 96% of nodules after 1 session, and could be up to 100% after 2 sessions. In our studies, we achieved a complete ablation rate of 90% on patients-basis. Recent evidences support that percutaneous local ablative therapy for small HCC is considered as effective as liver resection [1, 6]. In our study, survival rate at 1 year followed-up was 100%, with no treatment- related deaths, no major complications with only one local minor complication. Local recurrence rates varied from 12 - 36% at 6 months and from 16 - 38% at 12 months follow-up after RFA [3]. The reccurence rates in our study at 6 and 12 months were 23.33% and 30%, respectively . Junichi Toshimori et al studied 397 cases of HCC treated with RFA and reported that large tumor size (> 2 cm), tumor location (adjacent to major portal or hepatic vein/biliary duct or major visceral and diaphragm) and small ablated margin (< 3 mm) were independent predisposing factors for local recurrence after RFA [5]. In our study, we also noticed the same results with factors which contributed to recurrence were: tumor size > 2 cm (100% of local recurrence at 6 and 12 months had lesions larger than 2 cm), tumor in the difficult location to ablate (3 on 4 local recurrent lesions at 12 months) and uneffective post RFA antiviral treatment. CONCLUSION In conclusion, RFA is a safe and effective curative treatment for early-stage HCC, alternative to liver resection. Thus, the therapy is expanding its indications to help treat larger lesion with stronger ablative needle. T¹p chÝ y - d−îc häc qu©n sù sè 8-2020 181 REFERENCES 1. Andrea Salmi. Efficacy of radiofrequency ablation of hepatocellular carcinoma associated with chronic liver disease without cirrhosis. International Journal of Medical Sciences 2008; 5(6):327-332. 2. Bruix Jordi, Sherman Morris. Management of hepatocellular carcinoma: An update. Hepatology 2011:1020-1022. 3. Courtney L Scaife. Complication, local recurrence, and survival rates after radiofrequency ablation for hepatic malignancies. Surg Oncol Clin N Am 2003; 12:243-255. 4. Josep M Llovet. The Barcelona approach: Diagnosis, staging and treatment of hepatocellular carcinoma. Liver transplation 2004; 10(2-Suppl 1):S115-S120. 5. Junichi Toshimori. Local recurrence and complications after percutaneous radiofrequency ablation of hepatocellular carcinoma: A retrospective cohort study focused on tumor location. Acta Med Okayama 2015; 69(4):219-226. 6. Gugliemi A, Ruzzenante A. Radiofrequency ablation versus surgical resection for the treatment of small hepatocellular carcinoma in cirrhosis. J Gastrointest Surg 2008; 12(1):192-198. 7. Ronnie TP Poon. Locoregional therapies for hepatocellular carcinoma: A critical review from surgeon’s perspective. Annals of Surg 2002; 235(4):466-486. 8. SM Lin, CC Lin, Lin CJ, et al. Randomised controlled trial comparing percutaneous radiofrequency thermal ablation, percutaneous ethanol injection, percutaneous acetic acid injection to treat hepatocellular carcinoma of 3 cm or less. Gut 2005; 54(8):1151-1156.