Transarterial Embolization and Microwave Ablation Combination Therapy in Early-stage Hepatocellular Carcinoma: A Randomized Trial
Phase: NA
Conditions: Hepatocellular Carcinoma, Hepatoma, Liver Cancer, Adult, Liver Cell Carcinoma, Liver Cell Carcinoma, Adult
Sponsor: Wake Forest University Health Sciences

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Transarterial embolization and microwave ablation combination 
therapy in early-stage hepatocellular carcinoma: A randomized trial 
 
Project Lead:  Michael Fruscione 
Principal Investigator: Dionisios Vrochides, MD, PhD, FACS, FRCSC 
Coinvestigators: David A. Iannitti, MD, FACS; John B. Martinie, MD, FACS; and Erin 
Baker, MD 
Hepatopancreaticobiliary Division, Department of Surgery,  
Carolinas Medical Center 
Charlotte, North Carolina 28203 
 
 
 
 

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Summary 
This single-center, prospective RCT is designed to compare the outcomes and clinicopathologic results of 
blunt transarterial embolization (TAE) and microwave ablation (MWA) combination therapy with MWA 
monotherapy for the treatment of early (stages 0 and A) hepatocellular carcinoma (HCC). The primary 
aim of this study is to test the following hypothesis: 2-year intrahepatic disease-free survival does not 
differ between patients receiving the experimental therapy (MWA + TAE) and patients receiving the 
standard therapy (MWA alone) as treatment for early stage HCC. Secondary aims are: 1) to determine 
the clinical feasibility of TAE + MWA in HCC patients with a small tumor burden using patient 
demographics and disease characteristic data and 2) to determine the effect of TAE on radiographic 
tumor characteristics in this patient cohort. 
 
Principal Investigators 
Dionisios Vrochides, MD, PhD, FACS, FRCSC 
 
Co-Investigators 
David A. Iannitti, MD, FACS 
John B. Martinie, MD, FACS 
Erin Baker, MD 
 
Main Center 
Levine Cancer Institute, Carolinas Medical Center, Charlotte, NC 28203 
Sponsor 
Carolinas Healthcare Systems 
 
 
 
 

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Table of Contents 
 
BACKGROUND ............................................................................................................................................. 44 
STUDY DESIGN ............................................................................................................................................ 66 
Objective ................................................................................................................................................. 66 
Methods .................................................................................................................................................. 77 
Patient Eligibility and Allocation ......................................................................................................... 77 
Sample Size ......................................................................................................................................... 99 
Surgery ................................................................................................................................................ 10 
Data Collection ................................................................................................................................ 1111 
Statistical Analysis ........................................................................................................................... 1313 
ETHICAL AND SAFETY CONSIDERATIONS ................................................................................................ 1414 
Protection of Patients ......................................................................................................................... 1414 
Protection of health care providers .................................................................................................... 1414 
Protection of environment ................................................................................................................. 1515 
REFERENCES ............................................................................................................................................ 1717 
APPENDIX I: BCLC Classification of HCC .................................................................................................. 1919 
APPENDIX II. THE CLAVIEN-DINDO CLASSIFICATION OF SURGICAL COMPLICATIONS ............................ 2020 
APPENDIX III: LIVER IMAGING REPORTING AND DATA SYSTEM (LI-RADS) CRITERIA FOR HCC .............. 2121 
APPENDIX IV: DIAGNOSTIC WORK-UP/PATHWAY .................................................................................. 2222 
APPENDIX V: PERIOPERATIVE CARE PATHWAY FOR HCC ....................................................................... 2323 
APPENDIX VI: PHARMACOKINETIC PARAMETERS OF CHEMOTHERAPEUTIC AGENTS ........................... 2424 
 
 
 

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BACKGROUND 
According to the GLOBOCAN 2008 estimates, over 749,000 new cases of liver cancer are diagnosed and 
695,000 deaths from liver cancer occur worldwide each year1. Hepatocellular carcinoma (HCC) accounts 
for 75-90% of the total liver cancer burden worldwide and most often occurs in the setting of chronic 
liver disease and cirrhosis2. Surgical resection is the only treatment option that offers the potential of 
long-term survival; however, due to advanced, multifocal disease at diagnosis or lesions proximal to 
critical structures, fewer than 5% of patients are candidates for surgery. Overall 5-year survival following 
a diagnosis of HCC is <16%3. 
Prognostic variables including tumor status (number and size of nodules, vascular invasion, and N1 and 
M1 staging), liver function (Child-Pugh’s class, bilirubin, albumin, portal hypertension, ascites), and 
patient health (Eastern Cooperative Oncology Group (ECOG) performance status and symptomology) 
are used by the Barcelona-Clinic Liver Cancer (BCLC) guidelines for classification of HCC into 5 stages (0, 
A, B, C, and D) (Appendix I)4. This classification is intended to predict outcome and to enable appropriate 
treatment allocation for each HCC patient. Resection is recommended for patients with BCLC Stage 0 
(very early) disease, which is characterized by the presence of a single tumor <2 cm in diameter without 
vascular invasion/satellites in patients with good health status (ECOG-0) and well-preserved liver 
function (Child-Pugh A class)4. However, resection does not address the precancerous remnant liver, 
especially in the setting of cirrhosis, where progressive organ decompensation and ongoing 
hepatocarcinogenesis often lead to recurrence. The rate of recurrence of HCC at 5 years post-surgery is 
60–70%5,6, and the majority of these recurrences are limited to the liver and develop in the first 
postsurgical year6. Clearly, more effective operative techniques and treatment modalities are needed to 
improve clinical outcomes of surgical resections for early-stage HCC.  
Microwave ablation (MWA) has emerged as an accepted alternative to surgical resection for early-stage 
HCC. MWA delivers energy rapidly, directly, and uniformly into target tissues without the detrimental 
effects of tissue impedance experienced with radiofrequency ablation (RFA), which is also used often in 
the setting of early-stage HCC7. Multiple clinical trials have reported that percutaneous and operative 
MWA is safe and effective8-13, equivalent to RFA in terms of periprocedural morbidity14, and equivalent 
or superior to RFA in terms of local recurrence10,15-17 for treatment of primary and metastatic liver 
tumors. However, a recent retrospective outcome analysis of patients receiving RFA or MWA for early-
stage HCC reports a high rate of local recurrence in routine clinical practice18, which supports published 
recurrence rates of 10.5–24% following MWA in early-stage HCC19,20. Poorly-differentiated HCC and 

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pretreatment α-fetoprotein (AFP) were identified as independent predictors of local tumor progression 
in these patients18. Therefore, thermal ablation modalities have a proven role in the treatment of HCC, 
though their role in lieu of resection in early-stage HCC is currently under debate.  
Blunt transarterial embolization (TAE) is currently used predominantly as a palliative therapy for 
unresectable HCC21. In recent years, the technique of combining thermal ablation techniques with TAE 
has aimed to increase complete tumor response rates and reduce local recurrences. Randomized22 and 
nonrandomized23 trials comparing the combination treatment of TAE and RFA with RFA alone in patients 
with HCC lesions <3 cm in diameter show conflicting results in terms of overall survival and progression-
free survival. However, previously published reports have consistently found that the combination 
treatment carries equivalent risk of complications and mortality compared with thermal ablation 
alone24. Though use of MWA remains less common than RFA in this setting, recent investigations have 
demonstrated improved efficacy of MWA in combination with TAE for the treatment of large25 and 
small26 HCC lesions.    
Despite these suggested therapeutic benefits of combined thermal ablation and embolization 
techniques, little is known about the prognostic effects of MWA + TAE in early-stage HCC. To our 
knowledge, no RCTs have compared the combination therapy (MWA + TAE) with monotherapy (MWA 
alone) in this selective cohort. The efficacy of MWA in combination with TAE as a prophylactic treatment 
to reduce recurrence in HCC patients with a small tumor burden is unknown. Moreover, the optimal 
protocol and timing for MWA combined with TAE as a treatment for early stage HCC has yet to be 
determined. For all of these reasons, RCTs are required to examine the feasibility as well as the possible 
therapeutic and/or survival benefits of combination MWA + TAE in selected patients with early-stage 
HCC.      
 
 
 

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STUDY DESIGN 
 
Objective 
This single-center, prospective RCT is designed to compare the outcomes and clinicopathologic results of 
blunt transarterial embolization (TAE) and microwave ablation (MWA) combination therapy with MWA 
monotherapy for the treatment of early (stages 0 and A) hepatocellular carcinoma (HCC). The primary 
aim of this study is to test the following hypothesis: 2-year intrahepatic disease-free survival does not 
differ between patients receiving the experimental therapy (MWA + TAE) and patients receiving the 
standard therapy (MWA alone) as treatment for early-stage HCC. Secondary aims are: 1) to determine 
the clinical feasibility of TAE + MWA in HCC patients with a small tumor burden using patient 
demographics and disease characteristic data and 2) to determine the effect of TAE on radiographic 
tumor characteristics in this patient cohort.  
 
The primary outcome is 2-year intrahepatic disease-free survival, which is measured from time of 
randomization and is defined as the absence of local or regional recurrence of HCC as determined by 
diagnostic imaging. Local recurrence is defined as an enhancing lesion contiguous with the ablation zone 
that is present on subsequent imaging but was not present on the initial postablation scan. Regional 
recurrence is defined as hepatic recurrence that is not adjacent to the ablation site. 
 
Secondary outcome measures include: 
• 
Patient and disease characteristics (Table 1) 
• 
1-year, 2-year, 3-year, and 5-year overall survival; 
• 
1-year, 3-year, and 5-year intrahepatic disease-free survival;  
• 
Number of TAE procedures required (for multilobar lesions or repeat effect)   
• 
Toxicity induced by TAE and or MWA using the latest published full version of Common 
Terminology Criteria for Adverse Events (CTCAE v5.0 is slated for release in October 2015; CTCAE 
v4.0 is available currently)  
• 
1-month and 3-month postoperative morbidity using the Clavien-Dindo Classification of Surgical 
Complications27 (Appendix II); 
• 
1-month and 6-month postoperative mortality 

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• 
Ablation characteristics including tumor location by hepatic segment, proximity to a portal 
pedicle, number of applications, power settings, and ablation duration (per application and per 
tumor) 
• 
Radiologic tumor observations applied to the Liver Imaging Reporting and Data System (LI-RADS) 
criteria at 4-6 weeks post-ablation, every 3 months for the first 2 years, and every 6 months 
thereafter 
• 
AFP levels: baseline (preoperative/at diagnosis), 4-6 weeks post-ablation and TAE, every 3 
months for the first 2 years, and every 6 months thereafter 
• 
Return of bowel function (days), subdivided in: time until first stool, introduction of liquid or 
solid diet; 
• 
Length of hospital stay (days); 
• 
Length of ICU stay (days); 
• 
30- and 90-day readmission rates; 
• 
Return to normal activity (days), i.e., return to full activity, work, or sport; 
• 
Preoperative (baseline), 6-month and 1-year postoperative quality of life (QOL), using the 
Standard form 36 (SF-36 v 1.0) customized for HCC  
• 
For those patients who go on to resection:  
o Duration of resection operation (minutes), defined as incision to dressing time; 
o Correspondence between pre-randomization clinical/radiologic/laboratory evaluation 
and intraoperative findings 
 
Methods 
Patient Eligibility and Allocation 
Eligible patients will be identified in collaboration with the Levine Cancer Institute (LCI) at Carolinas 
Medical Center (CMC). The Institute functions as a series of integrated cancer programs distributing 
high-quality cancer care system-wide and houses nine cancer clinics, infusion therapy, palliative care 
and clinical trials, and state-of-the-art technology to connect member institutions across the Carolinas 
and worldwide. CMC is a high-volume center for the treatment of hepatocellular carcinoma and is one 
of only a few hospitals across the nation to utilize minimally invasive microwave ablative therapies to 
treat liver cancer. Approximately 60 MWA and several hundred TAE procedures are performed annually 

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with either an open, laparoscopic, or robot-assisted laparoscopic approach. The expected enrollment 
rate is 2 patients/month.   
Patients diagnosed with primary HCC classified as stage 0 (very early) or stage A (early) will be 
considered for inclusion in this study. Tumors will be staged preoperatively with computed tomography 
(CT) and/or magnetic resonance imaging (MRI). Laparoscopic ultrasound will be performed 
intraoperatively. 
Eligible patients will meet the following inclusion criteria: 
• 
Male or female patients aged ≥18 and ≤75 years 
• 
Primary diagnosis of HCC according to the guidelines published by the American Association for 
the Study of Liver Diseases (AASLD)28 and the diagnostic criteria used by the European 
Association for the Study of the Liver (EASL)29:  
o Two imaging techniques showing typical features of HCC; or 
o Cytologic/histologic diagnosis of HCC; or 
o Radiographic classification as LIRAD 5 (Appendix III), regardless of AFP level.  
• 
HCC classification of stage 0 (very early) or stage A (early) according to BCLC staging system 
criteria (Appendix I):  
o Solitary HCC lesion <3 cm in diameter 
o ≤3 HCC lesions, each ≤3.0 cm in diameter 
• 
Total bilirubin level, with or without portal hypertension, less than or equal to 3.0.  
• 
Adequate clinical condition to undergo laparoscopic or robot-assisted laparoscopic TAE and/or 
MWA as treatment for HCC 
• 
Willing and able to give informed consent 
Patients meeting the inclusion criteria will be subjected also to the following exclusion criteria: 
• 
Radiologic (CT or MRI) evidence of invasion into major portal/hepatic venous branches and no 
extrahepatic metastases (LR-5V or LR-M radiologic classifications)  
• 
Evidence of residual disease at first post-MWA CT examination  
• 
Body Mass Index (BMI) > 35 
• 
Previous history of hepatic resections 
• 
Severe renal dysfunction (creatinine clearance of <40 mL/min) 

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• 
Pregnant or nursing women      
According to a computer-generated variable size blocked randomization method, eligible patients will be 
allocated on a 1:1 basis to receive the experimental therapy (MWA + TAE) and standard therapy (MWA 
alone), respectively. The nature of the treatments and their possible adverse effects preclude the use of 
double-blind and double dummy techniques. In patients randomized to receive the experimental 
therapy, TAE treatments will be initiated within one week of randomization, then followed by MWA 
within 4 to 6 weeks after reviewing radiological scans from TAE. MWA will be performed 4 to 6 weeks 
following randomization in MWA standard therapy groups. Treatment may be discontinued if any 
exclusion criteria develop in the patient or at the patient’s request.  
Sample Size 
Power calculations are based upon expected 2-year survival rates. The main endpoint is 2-year 
intrahepatic disease-free survival, measured from the time of randomization which is measured from 
time of randomization and is defined as the absence of local or regional recurrence of HCC as 
determined by diagnostic imaging. Considering an estimated 80% and 90% intrahepatic disease-free 
survival at 2 years of follow-up for patients receiving MWA alone and MWA + TAE combination therapy, 
respectively, a sample size of 92 patients is required to detect a clinically meaningful 10% absolute 
difference in 2-year peritoneal disease-free survival with MWA + TAE with a minimum of 95% power and 
a 2-sided α = .05. To account for a 5–10% withdrawal rate (following intraoperative detection of vascular 
invasion or extrahepatic metastasis, etc.), a sample size of 100 patients is required (50 patients per arm). 
If the rate of patient enrollment is suboptimal, a covariate adaptive randomization method will be used 
to allocate patients in a 2:1 ratio to receive experimental therapy (MWA + TAE) and standard therapy 
(MWA alone), respectively, which would result in an overall sample size of 83 patients. 
 
Clinical Procedures 
Preprocedural Strategy 
Before randomization, patients will be assessed with either MRI or triphasic CT imaging and evaluated 
for baseline liver function, hematology, coagulation studies, and serum AFP. Liver function and 
underlying disease burden will be staged with the Child-Turcotte-Pugh criteria and the BCLC 
classification, respectively (Appendix IA and B). Radiologic findings will be reported according to the LI-
RADS criteria. Patient demographics, histologic analysis, and assessment of portal vein hypertension and 
its sequelae will also be recorded. Patients will receive pre-operative counseling.  

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Carolinas Medical Center follows already established Enhanced Recovery After Surgery (ERAS) SMART™ 
protocol for the pre-, intra-, and postoperative care of patients undergoing certain procedures in the 
hepatopancreatobiliary Division. Division-specific standard guidelines will be applied to the care of 
patients included in this study.  
Procedural Strategy 
For MWA and TAE procedures, patients will be given general anesthesia. In patients randomized to 
receive the experimental therapy, TAE treatments will be initiated within one week of randomization, 
then followed by MWA within 4 to 6 weeks after reviewing radiological scans from TAE. MWA will be 
performed 4 to 6 weeks following randomization in standard MWA therapy groups. Treatment may be 
discontinued if any exclusion criteria develop in the patient or at the patient’s request.  
For TAE procedures, moderate/procedural or general anesthesia will be induced.  A selective 5-F 
catheter will be introduced into the femoral vein, and visceral angiography will be performed to assess 
the arterial blood supply to the liver and to the lesion(s) identified on preprocedural imaging. All 
patients will undergo a distal super-selective catheterization of the hepatic arteries using a coaxial 
technique and microcatheters. Embolization will be performed with LC beads from BTG with a maximum 
size of 700 µm.  The LC beads will be admixed with 8-15 mL of contrast and injected into the arterial 
branch at a rate of 1-2 mL/min.  After embolization, angiography will be performed to determine the 
extent of vascular occlusion and to assess collateral tumor arterial supply. Patients will be observed 
carefully, and analgesia (morphine or meperidine) will be administered if necessary.  Given the small 
tumor size included in this study, bilobar lesions will be treated sequentially during the same 
interventional procedure. 
All operative MWAs will be performed in a laparoscopic or robot-assisted laparoscopic setting by one of 
four hepatobiliary surgeons with extensive experience with intraoperative US guidance and hepatic 
ablation (DI, JM, DV, EB). Care will be taken to create ample distance between the microwave near-field 
and any adjacent structures (diaphragm/heart, stomach/esophagus, colon, duodenum, gallbladder) by 
mobilization of the liver. All ablations will be guided by intraoperative ultrasound (BK Medical A/S, 
Herlev, Denmark) with care taken to allow for complete tumor treatment while preserving adequate 
distance between the microwave near-field and adjacent intrahepatic structures (portal pedicles, 
hepatic veins). Ablations will be performed with a 2.45-GHz generator with a 1.8-mm-diameter 
transcutaneous antenna (Acculis pMTA Accu2i; AngioDynamics Inc., Denmead, Hampshire, UK).  

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Operative variables will be recorded per patient, and individual ablation characteristics including tumor 
location by hepatic segment, proximity to a portal pedicle, number of applications, power settings, and 
ablation duration will be recorded for each individual tumor. A clearly demarcated zone of color flow 
Doppler activity will be visualized within 30 s of initiating the ablation to assure that the target is within 
the microwave ablation zone. Patients will be observed carefully, and analgesia will be administered per 
standard protocol if necessary. 
Postprocedural Strategy 
Division-specific standard guidelines will be applied to the postoperative care of patients included in this 
study.  Postoperative complications will be recorded and treated symptomatically. All patients will be 
closely followed up for disease progression with clinical and laboratory examinations 4–6 weeks after 
ablation/TAE procedures, then every 3 months for the first 2 years. At 4–6 weeks following TAE +/- 
MWA procedures, tumors will be assessed radiographically and characteristics will be reported 
according to the LI-RADS criteria and guidelines. Imaging techniques will then be performed every 3 
months during the first 2 years postoperative and every 6 months afterward. In addition, AFP levels will 
be obtained every 3 months during the first 2 years postoperative and every 6 months afterward.    
Data Collection 
All parameters will be prospectively collected. The study will be approved by the Internal Review Board 
of Carolinas Medical Center, and informed consent will be obtained from all patients prior to study 
participation. All hepatocellular carcinomas will be classified according to the TNM criteria of the 
American Joint Commission on Cancer (AJCC) 2010 Cancer System. A comprehensive medical history will 
be obtained from each patient and supplemented by clinical notes. Pre-, intra-, and postoperative 
variables (Table 1) and clinical outcomes will be recorded in an electronic database. Toxicity induced by 
TAE and or MWA will be graded according to the Common Terminology Criteria for Adverse Events - 
CTCAE v5.0 (Slated for release in October 2015; v4.3 available at 
http://evs.nci.nih.gov/ftp1/CTCAE/About.html).  
  
 
 

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Table 1. Variables for analysis  
Patient characteristics 
age, sex, viral hepatitis status, nicotine use, 
alcohol use, drug use, hypertension, obesity, 
diabetes mellitus, general conditions, prior 
therapy, underlying disease status as 
determined by Child-Pugh and MELD score 
Preoperative imaging 
presence of cirrhosis; tumor size, location and 
number  
Intraoperative findings 
surgeon performing procedures, proximity of 
tumor to portal pedicle, number of TAE 
applications, number of MWA applications, 
power settings, ablation duration (per 
application and per tumor), pathology from 
random liver biopsy 
Postoperative data 
Tumor radiology, length of stay, 30- and 90-day 
readmission, wound infection, postoperative 
complications (encephalopathy, liver failure, 
ascites, upper GI bleeding), postoperative 
ΔMELD score 
Tumor characteristics 
BCLC classification, Okuda stage, AJCC clinical 
tumor stage, venous infiltration, lymphatic 
infiltration  
Laboratory data 
 
α-fetoprotein (AFP) level, Hb, leukocytes, 
thrombocytes, serum proteins, albumin, 
bilirubin, γ-GT, ASAT, creatinine, INR, alkaline 
phosphatase  
Abbreviations: MELD, Model for End-Stage Liver Disease; TAE, transarterial chemoembolization; MWA, 
microwave ablation; GI, gastrointestinal; BCLC, Barcelona Clinic Liver Cancer; AJCC, American Joint Committee 
on Cancer; Hb, hemoglobin; γ-GT, gamma-glutamyl transpeptidase; ASAT, aspartate amino transferase; INR, 
international normalized ratio.  
 
Definitions   
Incomplete ablation is defined as enhancement present at the ablation border on arterial phase CT 
consistent with residual tumor on the initial post-ablation scan. Local recurrence is defined as an 
enhancing lesion contiguous with the ablation zone that is present on subsequent imaging but was not 
present on the initial postablation scan. Regional recurrence is defined as hepatic recurrence that is not 
adjacent to the ablation site. Metastatic recurrence is defined as extra-hepatic recurrence including 
lymph node metastases. Expected residual disease is defined as disease that was intentionally left 

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untreated at the initial MWA session. Further, liver-directed therapy is defined as any secondary hepatic 
ablation procedure for incomplete ablation or any recurrent disease. Survival will be calculated from the 
time of randomization until last recorded follow-up, liver transplantation, or death. 
Intrahepatic disease-free survival time is defined as the time between randomization and absence of 
local or regional recurrence of HCC as determined by diagnostic imaging. Overall survival will be 
measured as time from randomization until last recorded follow-up, liver transplantation, or death from 
any cause. Perioperative mortality is defined as in-hospital mortality.  
Quality of Life 
Quality of Life (QOL) will be assessed prospectively in a subgroup of patients who undergo follow-up 
examinations in the outpatient clinic of our facility. The data will be collected for a maximum of 5 years 
postoperatively or until patient death. Regular follow-up checkups will be offered to patients at 2-, 3-, or 
6-month intervals depending upon time elapsed from surgery, with frequency of checkups decreasing as 
postoperative period increases in duration.   
Statistical Analysis 
Patients alive at the time of analysis will be censored at the last follow-up examination or at liver 
transplantation. Univariate analyses will be performed using the log-rank test of equality for categorical 
variables and the chi-square test with Cox proportional hazard model for continuous variables to 
identify clinical variables (Child–Pugh class, Okuda class, Model for End-Stage Liver Disease (MELD) 
score, etiology of cirrhosis), tumor factors (extrahepatic disease, multicentric disease, tumor size, Milan 
criteria, AJCC tumor stage, AFP level), and treatment-related factors (TAE, complications, recurrence) 
predicting intrahepatic disease-free and overall survival. Survival and disease-free survival will be 
estimated using the Kaplan–Meier method and tested with the log-rank test following the intention-to-
treat principle. Statistical analysis will be performed using SAS software (SAS Institute, Cary, NC, USA). 
The analysis will be planned at a median follow-up of two years, with an interim analysis scheduled for 1 
year after the first patient is enrolled or when 50% of total expected enrollment has been reached.  
To improve patient selection in the future, additional exploratory analyses will be performed to identify 
potential prognostic factors. Table 1 details variables that will be included in a Cox proportional hazards 
regression model to obtain hazard ratios and 95% confidence intervals (CIs). All P values will be two-
sided and a p value < .05 will be considered significant. 

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ETHICAL AND SAFETY CONSIDERATIONS 
Protection of Patients 
The techniques and procedures used in this study protocol are not investigational or provisional in 
nature; rather, they are established in the provision of care for patients of the HPB Division at Carolinas 
Medical Center. The therapeutic benefit of combination of TAE/MWA treatment in this patient 
population remains unknown and is the focus of this study. The additive risk for adverse events is 
expected to be equal to the individual risks of the study procedures in this protocol.  
Standard Division-specific guidelines will be closely followed to ensure patient safety and clinical well-
being during all procedures. Patients will be closely monitored for complications associated with MWA 
and TAE, including wound complications, hematologic toxicities, and others. 
During the preparatory phase for procedures, the anesthesia personnel will evaluate the routine 
monitoring and support equipment. Several prophylactic actions may be employed to avert problems 
during the procedures. Adequate patient hydration prior to beginning the procedures will be ensured.  
Protection of health care providers  
Occupational health risks for health care providers include: 
• 
Exposure to hepatitis, HIV, tuberculosis, or any infectious process; 
• 
inadvertent inhalation of anesthetics; 
• 
exposure to intraoperative X-rays; and 
• 
Exposure to cytotoxic agents. 
Strict adherence to Universal Precautions will be ensured at all times. Any blood, body fluid, or tissue 
from any patient will be considered potentially contaminated. Gloves, gowns, masks, and eye protection 
will be used to prevent contact between any contaminated object and the staff. The following items, 
which are not included under Universal Precautions, will be required: 
 
• 
Use of unpowdered latex gloves. 
• 
Use of the smoke evacuator to remove aerosols and vapors. 
• 
Modifications to the routine operating room clean up. 

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• 
Recommended procedures for clean up of biohazardous or chemical spills. 
 
Certain equipment will be available and appropriately utilized by personnel who come in contact with 
cytotoxic agents. This equipment will include: unpowdered latex gloves, impervious sterile gowns, 
protective eye wear, respirator mask (if a spill occurs), a spill kit, an impenetrable hazardous waste 
container, specially marked linen bags, and appropriate cytotoxic agent labels. 
 
Protection of environment 
 
Strict adherence to Universal Precautions will be maintained. Any biohazardous material will be 
separated from the standard trash and linen and placed in appropriate receptacles by the operating 
room staff. Biological waste will be stored onsite for 48 hours, then disposed of by a licensed hazardous 
waste facility. Bactericidal solutions will not be used to clean contaminated items; instead, 70% 
isopropyl alcohol will be used for clean up as recommended by the Occupational Safety and Health 
Administration (OSHA). 
Clean up of biological waste spills will be directed by specific hospital policies and procedures that are 
based upon OSHA, Joint Commission on Accreditation of Healthcare Organizations (JCAHO) and National 
Cancer Institute (NCI) guidelines. All spills will be contained and cleaned up immediately by the 
circulating nurse. The procedures will be dictated by the size of the spill. If any personnel make direct 
contact with biological waste, they will be directed to remove immediately the contaminated apparel 
and discard it in a hazardous waste container. The affected skin will be immediately washed with pure 
soap. If the eyes are affected, they will be immediately flooded with water or isotonic saline for five 
minutes. The personnel will then report to occupational health or to the emergency room. If only the 
clothing is contaminated, the article will be removed as soon as possible and placed in an appropriate 
receptacle. 
 
 

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Figure 1. CONSORT flow diagram of patient participation 
 
 
 

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APPENDIX I:  
 
A: BCLC Classification of HCC 
 
 
 
 
B: Child-Turcotte-Pugh Liver Function Scoring System 
 
 
 
 

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APPENDIX II. THE CLAVIEN-DINDO CLASSIFICATION OF SURGICAL COMPLICATIONS 
 

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APPENDIX III: LIVER IMAGING REPORTING AND DATA SYSTEM (LI-RADS) CRITERIA FOR HCC 
 
 

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APPENDIX IV: DIAGNOSTIC WORK-UP/PATHWAY 
 
 
 
 
 
 

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APPENDIX V: PERIOPERATIVE CARE PATHWAY FOR HCC 
 
 
 
 

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APPENDIX VI: PHARMACOKINETIC PARAMETERS OF  LC Bead®  
 
The LC Bead® is a preformed, deformable microsphere consisting of a biocompatible, sulphonate-
modified, N-Fil hydrogel. LC Bead® comprise a range of hydrogel microspheres that are biocompatible, 
hydrophilic, nonresorbable and precisely calibrated. . The LC Bead® is available in 3 sizes ranging from 
100μm to 700μm   
 
PRESENTATION:  
• 
Glass vial of 10ml 
• 
Stopper sealed by an aluminum cap equipped with a colored cap 
• 
Each vial contains approximately 1ml or 2ml of LC Bead® in a 
• 
non-pyrogenic sterile physiological buffered saline. 
• 
Each vial is intended for single patient use only. Do not resterilize. Discard any unused material 
 
INDICATIONS:  
LC Bead® microspheres are intended to be used for the embolization of 
hypervascular tumors and arteriovenous malformations (AVMs). 
CONTRAINDICATIONS  
1. Patients intolerant to occlusion procedures. 
2. Vascular anatomy or blood flow that precludes catheter placement or emboli injection. 
3. Presence or likely onset of vasospasm. 
4. Presence or likely on set of hemorrhage. 
5. Presence of severe atheromatous disease. 
6. Presence of feeding arteries smaller than distal branches from which they emerge. 
7. Presence of patent extra-to-intracranial anastomoses or shunts. 
8. Presence of collateral vessel pathways potentially endangering normal territories during 
embolization. 
9. Presence of end arteries leading directly to cranial nerves. 
10. Presence of arteries supplying the lesion not large enough to accept LC Bead®microspheres. 
11. Vascular resistance peripheral to the feeding arteries precluding passage of LC 
Bead®microspheres into the lesion. 
12. Do not use LC Bead® microspheres in the following applications: Embolization of large diameter 
arteriovenous shunts (ie. where the blood does not pass through the arterial/capillary/venous 
transition but directly from artery to vein. 
i. 
The pulmonary arterial vasculature. 
ii. 
Any vasculature where the use of LC Bead® Embolic Agent could pass directly into the 
internal carotid artery or the above listed vessels. 

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