Trial Outcomes & Findings for Impact of Y90 Radiation Segmentectomy on HCC (NCT NCT03248375)

Last Updated: 2023-02-13

Results Overview

Efficacy of 90Yttrium (Y90) Radiation Segmentectomy on Unresectable Hepatocellular Carcinoma as measured by tumor response according to mRECIST. CR = Disappearance of any intratumoral arterial enhancement in all target lesions PR = At least a 30% decrease in the diameter of the viable (enhancement in the arterial phase) target lesion SD = Any cases that do not qualify for either partial response or progressive disease PD = An increase of at least 20% in the diameter of viable (enhancing) target lesion

Recruitment status

COMPLETED

Study phase

Target enrollment

29 participants

Primary outcome timeframe

2 years

Results posted on

2023-02-13

Participant Flow

Individuals were enrolled between Aug 3, 2016, and April 4, 2019

Participant milestones

Participant milestones
Measure	Radiation Segmentectomy Patients diagnosed with hepatocellular carcinoma underwent radiation segmentectomy on resectable hepatocellular carcinoma and cirrhosis HCC. Radiation segmentectomy was done with ⁹⁰Y microspheres infused through selective branches off the hepatic artery. The delivery device used was glass-based (TheraSphere; Boston Scientific, Ottawa, ON, Canada), in which ⁹⁰Y is an integral constituent of the biocompatible glass matrix. Estimated dose to the treated area was \>205Gy.
Overall Study STARTED	29
Overall Study COMPLETED	24
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Radiation Segmentectomy Patients diagnosed with hepatocellular carcinoma underwent radiation segmentectomy on resectable hepatocellular carcinoma and cirrhosis HCC. Radiation segmentectomy was done with ⁹⁰Y microspheres infused through selective branches off the hepatic artery. The delivery device used was glass-based (TheraSphere; Boston Scientific, Ottawa, ON, Canada), in which ⁹⁰Y is an integral constituent of the biocompatible glass matrix. Estimated dose to the treated area was \>205Gy.
Overall Study Lost to Follow-up	5

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Radiation Segmentectomy n=29 Participants Radiation Segmentectomy on Resectable HCC on patients diagnosed with hepatocellular carcinoma
Liver segment tumor distribution 1 - caudate lobe	0 Participants n=29 Participants
Age, Continuous	63.4 years STANDARD_DEVIATION 8.4 • n=29 Participants
Sex: Female, Male Female	6 Participants n=29 Participants
Sex: Female, Male Male	23 Participants n=29 Participants
Cause of liver disease Hepatitis B virus	3 Participants n=29 Participants
Cause of liver disease Hepatitis C virus	13 Participants n=29 Participants
Cause of liver disease Non-alcoholic steatohepatitis	5 Participants n=29 Participants
Cause of liver disease Alcohol	7 Participants n=29 Participants
Cause of liver disease Sarcoidosis	1 Participants n=29 Participants
Cause of liver disease Haemochromatosis	1 Participants n=29 Participants
Child-Pugh score A5	14 Participants n=29 Participants
Child-Pugh score A6	12 Participants n=29 Participants
Child-Pugh score B7	3 Participants n=29 Participants
α-Fetoprotein	5 ng/mL n=29 Participants
Albumin-bilirubin grade (ALBI) Albumin-bilirubin grade 1	7 Participants n=29 Participants
Albumin-bilirubin grade (ALBI) Albumin-bilirubin grade 2	22 Participants n=29 Participants
Ascites	1 Participants n=29 Participants
Tumor diameter	2.1 cm STANDARD_DEVIATION 0.4 • n=29 Participants
Liver segment tumor distribution 2 - left of the left hepatic vein and falciform ligament and superior to the portal plane	5 Participants n=29 Participants
Liver segment tumor distribution 3 - left of the left hepatic vein and falciform ligament and inferior to the portal plane	0 Participants n=29 Participants
Liver segment tumor distribution 4 - between the left and middle hepatic veins - subcardiac location	8 Participants n=29 Participants
Liver segment tumor distribution 5 - located below the portal plane between the middle and right hepatic veins	2 Participants n=29 Participants
Liver segment tumor distribution 6 - located below the portal plane to the right of the right hepatic vein	5 Participants n=29 Participants
Liver segment tumor distribution 7 - located above the portal plane to the right of the right hepatic vein	3 Participants n=29 Participants
Liver segment tumor distribution 8 - located above the portal plane between the middle and right hepatic veins	11 Participants n=29 Participants
Location Peripheral	28 Participants n=29 Participants
Location Central	1 Participants n=29 Participants
Number of injection locations 1	24 Participants n=29 Participants
Number of injection locations 2	5 Participants n=29 Participants
Lobar volume Right	896.7 mL n=29 Participants
Lobar volume Left	439.0 mL n=29 Participants
Perfused liver volume	153.6 mL STANDARD_DEVIATION 99.2 • n=29 Participants
Distribution of Perfused Liver Volumes <100 cc	9 Participants n=29 Participants
Distribution of Perfused Liver Volumes 100-200 cc	12 Participants n=29 Participants
Distribution of Perfused Liver Volumes >200 cc	8 Participants n=29 Participants
Lung shunt fraction (LSF)	4 percentage reaching lung n=29 Participants
Calculated dose to the perfused segment	584 Gy n=29 Participants

PRIMARY outcome

Timeframe: 2 years

Outcome measures

Outcome measures
Measure	Radiation Segmentectomy n=29 Participants Radiation Segmentectomy on Resectable HCC on patients diagnosed with hepatocellular carcinoma
Number of Participants With Local Tumor Response According to mRECIST CR - Complete response	26 Participants
Number of Participants With Local Tumor Response According to mRECIST SD - Stable disease	0 Participants
Number of Participants With Local Tumor Response According to mRECIST PR - Partial response	0 Participants
Number of Participants With Local Tumor Response According to mRECIST PD - Progressive disease	3 Participants

SECONDARY outcome

Timeframe: 2 years

Population: Data for participants who had target lesion progression only

Time until progression of the target lesion and overall disease based on mRECIST

Outcome measures

Outcome measures
Measure	Radiation Segmentectomy n=3 Participants Radiation Segmentectomy on Resectable HCC on patients diagnosed with hepatocellular carcinoma
Median Time to Progression (TTP)	NA days There was an insufficient number of participants with events to calculate a median TTP. Three patients had target lesion progression at 227, 496, and 668 days.

SECONDARY outcome

Timeframe: 1 year and 2 years

Cumulative incidence function estimation of the incidence of the occurrence of local progression (event) at 1 year and 2 years while taking the competing risk of transplant into account. Local progression was defined per modified Response Evaluation Criteria In Solid Tumors Criteria (mRECIST) for target lesions and assessed by MRI with local progression defined as an \>20% increase in the diameter of the viable (enhancing) target lesion, taking as a reference of the baseline enhancing tumor size.

Outcome measures

Outcome measures
Measure	Radiation Segmentectomy n=29 Participants Radiation Segmentectomy on Resectable HCC on patients diagnosed with hepatocellular carcinoma
Cumulative Incidence of Participants With Local Progression 1 years	4 percentage of participants Interval 0.0 to 16.0
Cumulative Incidence of Participants With Local Progression 2 years	12 percentage of participants Interval 3.0 to 28.0

SECONDARY outcome

Timeframe: 0 days

Population: Dose delivered to the tumour was calculated for 26 (90%) patients with 90Y PET CT imaging. Three (7%) patients were excluded due to technical issues.

The dose was calculated using PET/CT calculated dose estimation delivered to the tumor. Counts on PET/CT post-treatment were used to estimate the dose delivered to the tumor.

Outcome measures

Outcome measures
Measure	Radiation Segmentectomy n=26 Participants Radiation Segmentectomy on Resectable HCC on patients diagnosed with hepatocellular carcinoma
Quantifying Dose to Target Lesion	1004.6 Gy Interval 844.7 to 1400.8

SECONDARY outcome

Timeframe: For 2 years with visits 6 weeks post treatment then every 3 months since treatment for 24 months for assessment of laboratory and clinical symptoms

Number of treatment related adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events v 5.0 (CTCAE).

Outcome measures

Outcome measures
Measure	Radiation Segmentectomy n=29 Participants Radiation Segmentectomy on Resectable HCC on patients diagnosed with hepatocellular carcinoma
Number of Treatment-related Adverse Events fatigue	9 events
Number of Treatment-related Adverse Events nausea, vomiting, or anorexia	7 events
Number of Treatment-related Adverse Events abdominal discomfort	6 events
Number of Treatment-related Adverse Events ascites	1 events
Number of Treatment-related Adverse Events laboratory changes	24 events

SECONDARY outcome

Timeframe: For 2 years with visits 6 weeks post treatment then every 3 months since treatment for 24 months for assessment of laboratory and clinical symptoms

Number of participants with access site-related adverse events

Outcome measures

Outcome measures
Measure	Radiation Segmentectomy n=29 Participants Radiation Segmentectomy on Resectable HCC on patients diagnosed with hepatocellular carcinoma
Number of Participants With Access Site-related Adverse Events Arterial injury	1 Participants
Number of Participants With Access Site-related Adverse Events Hematoma (minor)	4 Participants
Number of Participants With Access Site-related Adverse Events None	24 Participants

SECONDARY outcome

Timeframe: For 2 years with visits 6 weeks post treatment then every 3 months since treatment for 24 months for assessment of laboratory changes

Population: All Patients

Number of participants with treatment-related laboratory adverse events assessed 6 weeks post-treatment then every 3 months since treatment for 24 months

Outcome measures

Outcome measures
Measure	Radiation Segmentectomy n=29 Participants Radiation Segmentectomy on Resectable HCC on patients diagnosed with hepatocellular carcinoma
Number of Participants With Treatment-related Laboratory Adverse Events ALP increased	4 Participants
Number of Participants With Treatment-related Laboratory Adverse Events Total blood bilirubin increased	4 Participants
Number of Participants With Treatment-related Laboratory Adverse Events Albumin decreased	6 Participants
Number of Participants With Treatment-related Laboratory Adverse Events Leukopenia	13 Participants
Number of Participants With Treatment-related Laboratory Adverse Events Anemia	3 Participants
Number of Participants With Treatment-related Laboratory Adverse Events Thrombocytopenia	6 Participants
Number of Participants With Treatment-related Laboratory Adverse Events AST or ALT increased	4 Participants
Number of Participants With Treatment-related Laboratory Adverse Events Creatinine increased	3 Participants
Number of Participants With Treatment-related Laboratory Adverse Events International normalised ratio increased	1 Participants

Adverse Events

Radiation Segmentectomy

Serious events: 0 serious events

Other events: 26 other events

Deaths: 1 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Radiation Segmentectomy n=29 participants at risk Radiation Segmentectomy on Resectable HCC on patients diagnosed with hepatocellular carcinoma
Injury, poisoning and procedural complications Arterial Injury	3.4% 1/29 • up to 2 years and every 3 months since treatment for 24 months for laboratory changes
Injury, poisoning and procedural complications Haemotoma	13.8% 4/29 • up to 2 years and every 3 months since treatment for 24 months for laboratory changes
General disorders Fatigue	31.0% 9/29 • up to 2 years and every 3 months since treatment for 24 months for laboratory changes
Gastrointestinal disorders Nausea, Vomiting, or Anorexia	24.1% 7/29 • up to 2 years and every 3 months since treatment for 24 months for laboratory changes
Gastrointestinal disorders Abdominal discomfort	20.7% 6/29 • up to 2 years and every 3 months since treatment for 24 months for laboratory changes
Gastrointestinal disorders Ascites	3.4% 1/29 • up to 2 years and every 3 months since treatment for 24 months for laboratory changes
Blood and lymphatic system disorders Leukopenia	44.8% 13/29 • up to 2 years and every 3 months since treatment for 24 months for laboratory changes
Blood and lymphatic system disorders Thrombocytopenia	20.7% 6/29 • up to 2 years and every 3 months since treatment for 24 months for laboratory changes
Blood and lymphatic system disorders Anaemia	10.3% 3/29 • up to 2 years and every 3 months since treatment for 24 months for laboratory changes
Hepatobiliary disorders AST or ALT increased	13.8% 4/29 • up to 2 years and every 3 months since treatment for 24 months for laboratory changes
Hepatobiliary disorders ALP increased	13.8% 4/29 • up to 2 years and every 3 months since treatment for 24 months for laboratory changes
Hepatobiliary disorders Total blood bilirubin increased	13.8% 4/29 • up to 2 years and every 3 months since treatment for 24 months for laboratory changes
Metabolism and nutrition disorders Albumin decreased	20.7% 6/29 • up to 2 years and every 3 months since treatment for 24 months for laboratory changes
Investigations Creatinine increased	10.3% 3/29 • up to 2 years and every 3 months since treatment for 24 months for laboratory changes
Investigations International normalised ratio increased	3.4% 1/29 • up to 2 years and every 3 months since treatment for 24 months for laboratory changes

Additional Information

Dr. Edward Kim

Icahn School of Medicine at Mount Sinai

Phone: (212) 241-7409

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place