Trial Outcomes & Findings for Study of ThermoDox With Standardized Radiofrequency Ablation (RFA) for Treatment of Hepatocellular Carcinoma (HCC) (NCT NCT02112656)

Last Updated: 2024-08-20

Results Overview

Overall survival is defined as the time (in months) from the date of randomization to the death from any cause or the end of the study.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

554 participants

Primary outcome timeframe

All subjects to be contacted every 3 months after radiological progression for vital status reporting. Subjects were followed for OS up to 68 months from randomization.

Results posted on

2024-08-20

Participant Flow

Participant milestones

Participant milestones
Measure	ThermoDox 50 mg/m2 ThermoDox plus standardized RFA using standardized treatment dwell time for solitary HCC lesions ≥ 3.0 cm to ≤ 7.0 cm ThermoDox: Thermally Sensitive Liposomal Doxorubicin 50 mg/m2 Single 30 minute intravenous infusion	Dummy Infusion standardized RFA alone using standardized treatment dwell time for solitary HCC lesions ≥ 3.0 cm to ≤ 7.0 cm Dummy infusion: Sodium Chloride 0.9% or 5% Dextrose (D5W), Single 30 minute intravenous infusion
Overall Study STARTED	277	277
Overall Study COMPLETED	187	178
Overall Study NOT COMPLETED	90	99

Reasons for withdrawal

Reasons for withdrawal
Measure	ThermoDox 50 mg/m2 ThermoDox plus standardized RFA using standardized treatment dwell time for solitary HCC lesions ≥ 3.0 cm to ≤ 7.0 cm ThermoDox: Thermally Sensitive Liposomal Doxorubicin 50 mg/m2 Single 30 minute intravenous infusion	Dummy Infusion standardized RFA alone using standardized treatment dwell time for solitary HCC lesions ≥ 3.0 cm to ≤ 7.0 cm Dummy infusion: Sodium Chloride 0.9% or 5% Dextrose (D5W), Single 30 minute intravenous infusion
Overall Study Death	78	82
Overall Study Withdrawal by Subject	9	11
Overall Study Lost to Follow-up	2	4
Overall Study Noncompliance	1	2

Baseline Characteristics

Study of ThermoDox With Standardized Radiofrequency Ablation (RFA) for Treatment of Hepatocellular Carcinoma (HCC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ThermoDox 50 mg/m2 n=277 Participants ThermoDox plus standardized RFA using standardized treatment dwell time for solitary HCC lesions ≥ 3.0 cm to ≤ 7.0 cm ThermoDox: Thermally Sensitive Liposomal Doxorubicin 50 mg/m2 Single 30 minute intravenous infusion	Dummy Infusion n=277 Participants standardized RFA alone using standardized treatment dwell time for solitary HCC lesions ≥ 3.0 cm to ≤ 7.0 cm Dummy infusion: Sodium Chloride 0.9% or 5% Dextrose (D5W), Single 30 minute intravenous infusion	Total n=554 Participants Total of all reporting groups
Age, Continuous	62 years n=99 Participants	62 years n=107 Participants	62 years n=206 Participants
Sex: Female, Male Female	54 Participants n=99 Participants	65 Participants n=107 Participants	119 Participants n=206 Participants
Sex: Female, Male Male	223 Participants n=99 Participants	212 Participants n=107 Participants	435 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	265 Participants n=99 Participants	257 Participants n=107 Participants	522 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) White	12 Participants n=99 Participants	19 Participants n=107 Participants	31 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants

PRIMARY outcome

Timeframe: All subjects to be contacted every 3 months after radiological progression for vital status reporting. Subjects were followed for OS up to 68 months from randomization.

Population: Intent-to-treat (ITT) population

Overall survival is defined as the time (in months) from the date of randomization to the death from any cause or the end of the study.

Outcome measures

Outcome measures
Measure	ThermoDox 50 mg/m2 n=277 Participants ThermoDox plus standardized RFA using standardized treatment dwell time for solitary HCC lesions ≥ 3.0 cm to ≤ 7.0 cm ThermoDox: Thermally Sensitive Liposomal Doxorubicin 50 mg/m2 Single 30 minute intravenous infusion	Dummy Infusion n=277 Participants standardized RFA alone using standardized treatment dwell time for solitary HCC lesions ≥ 3.0 cm to ≤ 7.0 cm Dummy infusion: Sodium Chloride 0.9% or 5% Dextrose (D5W), Single 30 minute intravenous infusion
Overall Survival (OS)	58.06 Months Interval 45.53 to Not estimable (NA) due to insufficient number of participants reached the event at time of final analysis.	NA Months Interval 47.93 to Not estimable (NA) due to insufficient number of participants reached the event at time of final analysis.

SECONDARY outcome

Timeframe: CT or MRI scan (Chest, Abdomen, Pelvis) done at Baseline and Day 28. Additional imaging done at months 5, 9, 13, 17, 21, 25, then every 6 months until disease progression is seen. Study subjects were followed up to 63 months after randomization.

Population: Intent-to-treat (ITT) population

The protocol incorporates modified RECIST developed for HCC clinical research as a basis to evaluate tumor response. PFS here is defined as the time (in months) from the date of randomization to the first date on which one of the following occurs (as determined by CT or MRI scan): * Death of any cause * Treatment failure (inability to achieve CR after two RFA ± ThermoDox treatment sessions) * Progression due to local tumor recurrence after initial CR * Progression due to distant intrahepatic tumor recurrence * Progression due to extrahepatic tumor recurrence

Outcome measures

Outcome measures
Measure	ThermoDox 50 mg/m2 n=277 Participants ThermoDox plus standardized RFA using standardized treatment dwell time for solitary HCC lesions ≥ 3.0 cm to ≤ 7.0 cm ThermoDox: Thermally Sensitive Liposomal Doxorubicin 50 mg/m2 Single 30 minute intravenous infusion	Dummy Infusion n=277 Participants standardized RFA alone using standardized treatment dwell time for solitary HCC lesions ≥ 3.0 cm to ≤ 7.0 cm Dummy infusion: Sodium Chloride 0.9% or 5% Dextrose (D5W), Single 30 minute intravenous infusion
Progression-free Survival (PFS)	19.31 Months Interval 15.72 to 25.2	16.78 Months Interval 12.86 to 21.32

Adverse Events

ThermoDox 50 mg/m2

Serious events: 73 serious events

Other events: 265 other events

Deaths: 78 deaths

Dummy Infusion

Serious events: 33 serious events

Other events: 216 other events

Deaths: 82 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Imunon, Inc.

Phone: (609) 896-9100

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI shall seek the Sponsor's prior review of publications, not before the multi-center publication has been published with Sponsor or 1 year from the date of Study completion/termination and only after review and comment by Sponsor. Proposed publication must be provided to Sponsor at least 60 days prior to submission to publisher. On Sponsor request, PI shall withhold a Publication from submission an additional 60 days to allow for the filing of a patent or any other protective actions available.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	ThermoDox 50 mg/m2 n=274 participants at risk ThermoDox plus standardized RFA using standardized treatment dwell time for solitary HCC lesions ≥ 3.0 cm to ≤ 7.0 cm ThermoDox: Thermally Sensitive Liposomal Doxorubicin 50 mg/m2 Single 30 minute intravenous infusion	Dummy Infusion n=273 participants at risk standardized RFA alone using standardized treatment dwell time for solitary HCC lesions ≥ 3.0 cm to ≤ 7.0 cm Dummy infusion: Sodium Chloride 0.9% or 5% Dextrose (D5W), Single 30 minute intravenous infusion
General disorders Oedema Peripheral	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
General disorders Multi-Organ Failure	0.00% 0/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Hepatobiliary disorders Portal Vein Thrombosis	0.73% 2/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Hepatobiliary disorders Cholecystitis Acute	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Hepatobiliary disorders Hepatic Failure	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Hepatobiliary disorders Hepatic Infarction	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Hepatobiliary disorders Cholelithiasis	0.00% 0/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Hepatobiliary disorders Hepatic Cirrhosis	0.00% 0/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Hepatobiliary disorders Hepatic Function Abnormal	0.00% 0/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Hepatobiliary disorders Ischaemic Hepatitis	0.00% 0/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Cardiac disorders Acute Myocardial Infarction	0.73% 2/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Cardiac disorders Tachycardia	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Cardiac disorders Atrial Fibrillation	0.00% 0/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Cardiac disorders Atrioventricular Block Complete	0.00% 0/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Cardiac disorders Bradycardia	0.00% 0/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Injury, poisoning and procedural complications Overdose	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Injury, poisoning and procedural complications Procedural Intestinal Perforation	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Injury, poisoning and procedural complications Procedural Pain	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Injury, poisoning and procedural complications Brachial Plexus Injury	0.00% 0/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Injury, poisoning and procedural complications Post Procedural Complication	0.00% 0/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Injury, poisoning and procedural complications Post Procedural Discharge	0.00% 0/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Injury, poisoning and procedural complications Post Procedural Haematoma	0.00% 0/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Injury, poisoning and procedural complications Post Procedural Inflammation	0.00% 0/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Nervous system disorders Cerebrovascular Accident	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Nervous system disorders Headache	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Nervous system disorders Hepatic Encephalopathy	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary Haemorrhage	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.00% 0/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	1.5% 4/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.00% 0/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Immune system disorders Drug Hypersensitivity	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Immune system disorders Immunosuppression	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Metabolism and nutrition disorders Decreased Appetite	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Metabolism and nutrition disorders Hyponatraemia	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Endocrine disorders Adrenocortical Insufficiency Acute	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Small Cell Lung Cancer	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour Haemorrhage	0.00% 0/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Renal and urinary disorders Urinary Retention	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Renal and urinary disorders Renal Failure Acute	0.00% 0/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.

Other adverse events
Measure	ThermoDox 50 mg/m2 n=274 participants at risk ThermoDox plus standardized RFA using standardized treatment dwell time for solitary HCC lesions ≥ 3.0 cm to ≤ 7.0 cm ThermoDox: Thermally Sensitive Liposomal Doxorubicin 50 mg/m2 Single 30 minute intravenous infusion	Dummy Infusion n=273 participants at risk standardized RFA alone using standardized treatment dwell time for solitary HCC lesions ≥ 3.0 cm to ≤ 7.0 cm Dummy infusion: Sodium Chloride 0.9% or 5% Dextrose (D5W), Single 30 minute intravenous infusion
Blood and lymphatic system disorders Neutropenia	49.6% 136/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	1.8% 5/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Blood and lymphatic system disorders Leukopenia	10.2% 28/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	1.5% 4/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Blood and lymphatic system disorders Febrile Neutropenia	4.4% 12/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Blood and lymphatic system disorders Anaemia	3.3% 9/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	1.8% 5/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Blood and lymphatic system disorders Leukocytosis	2.9% 8/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	1.1% 3/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Blood and lymphatic system disorders Thrombocytopenia	2.2% 6/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	1.8% 5/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Blood and lymphatic system disorders Bone Marrow Failure	1.1% 3/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Blood and lymphatic system disorders Pancytopenia	1.1% 3/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Blood and lymphatic system disorders Lymphopenia	0.73% 2/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Blood and lymphatic system disorders Disseminated Intravascular Coagulation	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Skin and subcutaneous tissue disorders Alopecia	51.8% 142/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Skin and subcutaneous tissue disorders Rash Erythematous	0.73% 2/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Skin and subcutaneous tissue disorders Urticaria	0.73% 2/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Skin and subcutaneous tissue disorders Decubitus Ulcer	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Skin and subcutaneous tissue disorders Ecchymosis	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Skin and subcutaneous tissue disorders Madarosis	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Skin and subcutaneous tissue disorders Nail Discolouration	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Skin and subcutaneous tissue disorders Pruritus	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Skin and subcutaneous tissue disorders Rash	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Skin and subcutaneous tissue disorders Rash Maculo-Papular	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Skin and subcutaneous tissue disorders Skin Exfoliation	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Skin and subcutaneous tissue disorders Skin Reaction	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Skin and subcutaneous tissue disorders Subacute Cutaneous Lupus Erythematosus	0.36% 1/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Skin and subcutaneous tissue disorders Blister	0.00% 0/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Skin and subcutaneous tissue disorders Dermatitis Allergic	0.00% 0/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Skin and subcutaneous tissue disorders Dermatitis Atopic	0.00% 0/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Skin and subcutaneous tissue disorders Skin Ulcer	0.00% 0/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.37% 1/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Investigations Neutrophil Count Decreased	26.6% 73/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	1.5% 4/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Investigations White Blood Cell Count Decreased	24.1% 66/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	1.1% 3/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Investigations Alanine Aminotransferase Increased	13.1% 36/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	16.5% 45/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Investigations Aspartate Aminotransferase Increased	12.8% 35/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	21.2% 58/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Investigations Platelet Count Decreased	6.9% 19/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	1.5% 4/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Investigations Blood Bilirubin Increased	4.0% 11/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	2.6% 7/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Investigations Neutrophil Count Increased	2.9% 8/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.73% 2/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Investigations Neutrophil Percentage Decreased	2.9% 8/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Investigations Haemoglobin Decreased	2.6% 7/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Investigations Monocyte Percentage Increased	2.6% 7/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.00% 0/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Investigations White Blood Cell Count Increased	2.6% 7/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	0.73% 2/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Investigations Bilirubin Conjugated Increased	2.2% 6/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	1.1% 3/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.
Investigations Blood Pressure Increased	2.2% 6/274 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.	2.6% 7/273 • Assess adverse events (AEs) through Day 28 following study treatment. AEs after Day 28 evaluated as possibly, probably or definitely related to the study treatment or the RFA procedure were recorded at any point during the trial and are to be followed until resolution or the patient is clinically stable. In general, all subjects were followed up to 68 months for AE's. Serious and Other (Not Including Serious) Adverse Events monitored/assessed for the safety-evaluable population and All-Cause Mortality monitored/assessed represent participants who received study treatment.