Adjuvant Radiotherapy for Resected Hepatocellular Carcinoma With MVI

• Sponsor: Eastern Hepatobiliary Surgery Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT04891874
• Collaborator: (none)
• Enrollment: 76
• Location: 1
• Arms: 2
• Actual Duration (Months): 65
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

Positive micro vascular invasion in early stage hepatocellular carcinoma(HCC) leads to early recurrence after surgery. Adjuvant external radiotherapy will be applied in those patients to see if disease free survival and overall survival could be approved.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Radiation: Stereotactic radiotherapy	N/A

Detailed Description

Hepatocellular carcinoma(HCC) ranks the 6th most common cancer and is the 2nd leading cause of cancer-related death globally. Surgical resection remains the most efficient therapy in early stage. Though an anatomical resection of tumor lead to an up to 70% 5-year overall survival, the existence of micro vascular invasion(MVI) caused early recurrence. Stereotactic body radiation therapy (SBRT) has been proved to be efficient in treating vascular tumor thrombosis. The investigators tried to implement this technique in adjuvant setting for HCC after surgery with MVI. Participants with early stage HCC whose tumor locates closely to the main intrahepatic vascular will be regarded as potentially-not-enough-surgical-margin candidates. Surgical resection will be carried out as scheduled and an additional silver clip will be put into the margin. Postoperative pathological examination will detect micro vascular invasion or daughter nodule. MVI-positive candidates will be eligible for enrollment. Eligible participants will be randomized to two groups, SBRT group and surgery-alone(SA) group with 1-to-1 ratio. Participants in SBRT group will receive a 35Gy limited resection margin parenchyma SBRT after surgery, while participants in SA group just get surgery. Radiation related adverse events (AE) or reaction will be recorded and intervened necessarily. All participants will be followed up by investigators every three months. DFS, OS, and AEs are end points in this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 76 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Adjuvant SBRT after surgery group vs. surgery alone group.Adjuvant SBRT after surgery group vs. surgery alone group.
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Adjuvant Stereotactic Body Radiation for Hepatocellular Carcinoma With Microvascular Invasion and Narrow Resection Margin
• Actual Study Start Date: Aug 1, 2015
• Actual Primary Completion Date: Dec 31, 2020
• Actual Study Completion Date: Dec 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SBRT group Participants in SBRT group will receive SBRT as adjuvant radiotherapy for hepatocellular carcinoma with microvascular invasion and narrow resection margin.	Radiation: Stereotactic radiotherapy; Radiation using stereotactic radiotherapy device.
No Intervention: Surgery alone group Participants in surgery alone group will not receive any adjuvant therapy after surgery for hepatocellular carcinoma.

Outcome Measures

Primary Outcome Measures

1. Participants Without Recurrence (Disease-free). [DFS rate at 5-years after randomization.]

   Participants will be monitored for recurrence(disease) since enrollment. DFS was defined as time interval from randomization to the first recurrence. The unit of measure was month.

Secondary Outcome Measures

1. Overall Survival (OS) Rate. [OS rate at 5-years from randomization.]

   OS was defined as time interval from randomization to death.

Other Outcome Measures

1. Number of Participants Occured Adverse Events(AE) [AE will be evaluated up to 3 months after radiotherapy in SBRT group]

   AE was defined as side effect related to the radiotherapy

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. solitary nodule;

2. tumor adjacent to the main trunk of hepatic vein, cava vena, or to the major branch of portal vein (including the lobar branch at least);

3. macro-vascular negative;

4. no previous treatment before surgery;

5. no previous hepatic surgery;

6. Child-Pugh score A for hepatic function.

Exclusion Criteria:

1. spontaneous rupture;

2. pathologically proved positive resection margin;

3. severe cirrhosis with hypersplenism or esophageal and gastric varices;

4. 4-weeks postoperative examination revealed α-fetal protein(AFP) still positive or new lesion in remnant liver;

5. postoperative complications required a secondary operation or more than 3 weeks'recovery from surgery.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Second Military Medical University	Shanghai	Shanghai	China	200438

Sponsors and Collaborators

• Eastern Hepatobiliary Surgery Hospital

Investigators

• Principal Investigator: Jiamei Yang, MD, Secondary Military Medical Unversity, Shanghai

Study Documents (Full-Text)

• Study Protocol - Aug 1, 2015
• Statistical Analysis Plan - Aug 1, 2015
• Informed Consent Form - Aug 1, 2015

More Information

Publications

None provided.

• Responsible Party: Changying Shi, Principal Investigator, Eastern Hepatobiliary Surgery Hospital
• ClinicalTrials.gov Identifier: NCT04891874
• Other Study ID Numbers: Eastern HSH
• First Posted: May 19, 2021
• Last Update Posted: Sep 10, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Changying Shi, Principal Investigator, Eastern Hepatobiliary Surgery Hospital: Stereotactic body radiotherapy; Micro vascular invasion; Narrow resection margin
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular

Study Results

Participant Flow

Arm/Group Title	SBRT Group	Surgery Alone Group
Arm/Group Description	Participants in SBRT group will receive SBRT as adjuvant radiotherapy for hepatocellular carcinoma with microvascular invasion and narrow resection margin. Stereotactic radiotherapy: Radiation using stereotactic radiotherapy device.	Participants in surgery alone group will not receive any adjuvant therapy after surgery for hepatocellular carcinoma.
Period Title: Overall Study
STARTED	38	38
COMPLETED	38	38
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	SBRT Group	Surgery Alone Group	Total
Arm/Group Description	Participants in SBRT group will receive SBRT as adjuvant radiotherapy for hepatocellular carcinoma with microvascular invasion and narrow resection margin. Stereotactic radiotherapy: Radiation using stereotactic radiotherapy device.	Participants in surgery alone group will not receive any adjuvant therapy after surgery for hepatocellular carcinoma.	Total of all reporting groups
Overall Participants	38	38	76
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	34 89.5%	35 92.1%	69 90.8%
>=65 years	4 10.5%	3 7.9%	7 9.2%
Sex: Female, Male (Count of Participants)
Female	5 13.2%	6 15.8%	11 14.5%
Male	33 86.8%	32 84.2%	65 85.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	38 100%	38 100%	76 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
China	38 100%	38 100%	76 100%
Hepatitis Virus (Number of Participants With Hepatitis Vi) [Number]
Number [Number of Participants With Hepatitis Vi]	38 100%	38 100%	76 100%

Outcome Measures

1. Primary Outcome

Title	Participants Without Recurrence (Disease-free).
Description	Participants will be monitored for recurrence(disease) since enrollment. DFS was defined as time interval from randomization to the first recurrence. The unit of measure was month.
Time Frame	DFS rate at 5-years after randomization.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SBRT Group	Surgery Alone Group
Arm/Group Description	Participants in SBRT group will receive SBRT as adjuvant radiotherapy for hepatocellular carcinoma with microvascular invasion and narrow resection margin. Stereotactic radiotherapy: Radiation using stereotactic radiotherapy device.	Participants in surgery alone group will not receive any adjuvant therapy after surgery for hepatocellular carcinoma.
Measure Participants	38	38
Count of Participants [Participants]	16 42.1%	28 73.7%

2. Secondary Outcome

Title	Overall Survival (OS) Rate.
Description	OS was defined as time interval from randomization to death.
Time Frame	OS rate at 5-years from randomization.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SBRT Group	Surgery Alone Group
Arm/Group Description	Participants in SBRT group will receive SBRT as adjuvant radiotherapy for hepatocellular carcinoma with microvascular invasion and narrow resection margin. Stereotactic radiotherapy: Radiation using stereotactic radiotherapy device.	Participants in surgery alone group will not receive any adjuvant therapy after surgery for hepatocellular carcinoma.
Measure Participants	38	38
Count of Participants [Participants]	29 76.3%	20 52.6%

3. Other Pre-specified Outcome

Title	Number of Participants Occured Adverse Events(AE)
Description	AE was defined as side effect related to the radiotherapy
Time Frame	AE will be evaluated up to 3 months after radiotherapy in SBRT group

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SBRT Group	Surgery Alone Group
Arm/Group Description	Participants in SBRT group will receive SBRT as adjuvant radiotherapy for hepatocellular carcinoma with microvascular invasion and narrow resection margin. Stereotactic radiotherapy: Radiation using stereotactic radiotherapy device.	Participants in surgery alone group will not receive any adjuvant therapy after surgery for hepatocellular carcinoma.
Measure Participants	38	38
Count of Participants [Participants]	12 31.6%	0 0%

Adverse Events

Time Frame	3 months from radiotherapy.
Adverse Event Reporting Description	The adverse events were reported according to the CTCAE 5.0 version.
Arm/Group Title	SBRT Group		Surgery Alone Group
Arm/Group Description	Participants in SBRT group will receive SBRT as adjuvant radiotherapy for hepatocellular carcinoma with microvascular invasion and narrow resection margin. The AE like fatigue, vomitting, skin reaction and other items according to CTCAE5.0 will be recorded.		Participants in surgery alone group will not receive any adjuvant therapy after surgery for hepatocellular carcinoma.
All Cause Mortality
	SBRT Group		Surgery Alone Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/38 (0%)
Serious Adverse Events
	SBRT Group		Surgery Alone Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/38 (0%)		0/38 (0%)
Other (Not Including Serious) Adverse Events
	SBRT Group		Surgery Alone Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/38 (31.6%)		0/38 (0%)
Blood and lymphatic system disorders
Myelosuppression	2/38 (5.3%)	2	0/38 (0%)	0
Gastrointestinal disorders
Abdominal distension	2/38 (5.3%)	2	0/38 (0%)	0
Dyspepsea	2/38 (5.3%)	2	0/38 (0%)	0
Nausea	3/38 (7.9%)	3	0/38 (0%)	0
General disorders
Fatigue	9/38 (23.7%)	9	0/38 (0%)	0
Hepatobiliary disorders
Liver injury	2/38 (5.3%)	2	0/38 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.