الفهرس 
AcknowledgementOnly 14 pages are availabe for public view
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Abstract
Hepatocellular carcinoma (HCC) a global health challenge being ranked as the fifth most common cancer in the world and the second most common cause of cancer death in men. The majority of HCC cases are diagnosed at advanced stages when curable treatment options cannot be offered and only symptomatic or supportive interventions are available.
Local ablation is established as a potentially curative therapy for very-early and early-stage HCCs with results comparable to liver resection. Also, it has been used as a bridging therapy before liver transplantation. Additional advantages of local ablation include reduced costs and morbidity with less need for training and operative wards with shorter hospital stay.
Radiofrequency ablation (RFA) and microwave ablation (MWA) are the most widely used ablations techniques nowadays with contradictory results on comparing effectiveness and complications of both of them. Therefore, several studies have been conducted to fill this gap.
Our study aimed firstly to evaluate the therapeutic effectiveness of RFA versus MWA in terms of patients’ survival and tumor recurrence. Secondly, to investigate the most important prognostic factors that may influence those patients’ survival or tumor recurrence at the post-ablation time. Thirdly, to test markers of systemic inflammation including lymphocytes monocytes ratio (LMR) and neutrophil lymphocytes ratio (NLR) that may serve as effective prognostic tools to predict patients’ outcomes in this cohort. And finally, to demonstrate the effect of HCV viraemia on HCC patients’ outcome following local ablation using RFA or MWA.
After gaining proper research authorization (Institutional Review Board approval at Mayo Clinic, USA), we conducted this cohort study on HCC patients undergoing local ablation (a retrospective part including electronic patients’ data (from January 2000 till December 2016 and prospective part including patients from January 2017 till September 1st 2020).
Patients included were all adults (≥18 years) presented to the Gastroenterology and Hepatology Department, Mayo Clinic Rochester with HCC diagnosis and underwent local ablation using RFA or MWA as a treatment. Patients were excluded if they underwent other uncommon ablation techniques (percutaneous ethanol injection, cryoablation, laser ablation), had local ablation combined with other treatments e.g., embolic therapy, presented with recurrent HCC, presented with secondaries from extra-hepatic primary tumors, had incomplete data at the diagnosis, treatment or follow up time-points, had loss of follow up or declined the study consent.
Finally, 221 patients were included in the statistical analysis; 140 underwent RFA and 81 patients underwent MWA for HCC. We proposed 2 types of outcomes; Overall survival (OS); defined as the time period from HCC ablation (RFA or MWA) till death or last follow-up date and Disease-free survival (DFS); defined as the time to relapse (identification of tumor recurrence on imaging) or death, whichever came first.
Patients were evaluated for tumor recurrence using Contrast-enhanced multiphase Computed tomography (CECT) and/or Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) immediately following ablation, and at a 3 to 6-month intervals during the first 2 years and approximately every 6 months subsequently until death or September 1st, 2020.
We explored the influence of demographic, clinical, and laboratory and radiological factors on outcomes of HCC patients receiving RFA or MWA. On comparing RFA versus MWA, we couldn’t find any significant differences in ablation effectiveness. local tumor recurrence rate was non significantly higher in the RFA group versus the MWA group (62.1% vs 53%, P= 0.187). Moreover, There were no significant differences in OS or DFS between both treatments.
Univariate analysis of the factors associated with OS revealed that portal hypertension, tumor size, tumors number, Child Pugh score, BCLC staging, hypercholesteremia, MELD score, pre-ablation LMR and NLR were significantly associated with OS. However, multivariate analysis revealed that only tumor size, tumors number, MELD score and pre-ablation LMR and NLR were significantly associated with OS.
On the other side, Univariate analysis of the factors associated with DFS demonstrated that portal hypertension, tumor size, tumors number, Child Pugh score, BCLC staging, log² AFP, MELD score, pre-ablation LMR and NLR were significantly associated with DFS. However, multivariate analysis revealed that tumor size, tumors number, MELD score, log² AFP and pre-ablation LMR and NLR were significantly associated with DFS.
We found that chronic HCV viraemia was associated with 0.37 folds increase in risk of death and/or recurrence highlighting the need for proper management of chronic HCV infection in patients with HCV-induced HCC receiving local ablation.
In conclusion, RFA and MWA of HCC have comparable effectiveness, tumor recurrence rate, overall survival and disease-free survival. Factors associated with overall survival and disease-free survival are tumor size, tumor number, MELD score, lower pre-ablation LMR, higher pre-ablation NLR. While, pre-ablation AFP
is significantly associated with disease-free survival only.
Recommendations
• Further studies with increasing sample size are recommended for confirmation of our results.
• Global risk evaluation in HCC patients receiving local ablation using RFA or MWA is of paramount significance and is the main determinant of the subsequent clinical course in those patients.
• HCC biological characteristics (tumors number, tumors size and AFP) and liver functional reserve could be precise prognostic tools in patients treated with RFA or MWA.
• Further studies evaluating other HCC treatment modalities and increasing sample size are recommended to select the ablation method with the best outcome.
• Further studies testing the utility of the systemic inflammatory markers pre- and post-ablation to evaluate its prognostic value.