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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SBRT group | Experimental | Participants in SBRT group will receive SBRT as adjuvant radiotherapy for hepatocellular carcinoma with microvascular invasion and narrow resection margin. |
|
| Surgery alone group | No Intervention | Participants in surgery alone group will not receive any adjuvant therapy after surgery for hepatocellular carcinoma. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Stereotactic radiotherapy | Radiation | Radiation using stereotactic radiotherapy device. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Participants Without Recurrence (Disease-free). | 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. | DFS rate at 5-years after randomization. |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) Rate. | OS was defined as time interval from randomization to death. | OS rate at 5-years from randomization. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Occured Adverse Events(AE) | AE was defined as side effect related to the radiotherapy | AE will be evaluated up to 3 months after radiotherapy in SBRT group |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jiamei Yang, MD | Secondary Military Medical Unversity, Shanghai | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Second Military Medical University | Shanghai | Shanghai Municipality | 200438 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35303509 | Derived | Shi C, Li Y, Geng L, Shen W, Sui C, Dai B, Lu J, Pan M, Yang J. Adjuvant stereotactic body radiotherapy after marginal resection for hepatocellular carcinoma with microvascular invasion: A randomised controlled trial. Eur J Cancer. 2022 May;166:176-184. doi: 10.1016/j.ejca.2022.02.012. Epub 2022 Mar 15. |
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| ID | Title | Description |
|---|---|---|
| FG000 | SBRT Group | 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. |
| FG001 | Surgery Alone Group | Participants in surgery alone group will not receive any adjuvant therapy after surgery for hepatocellular carcinoma. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | SBRT Group | 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. |
| BG001 | Surgery Alone Group |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Participants Without Recurrence (Disease-free). | 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. | Posted | Count of Participants | Participants | DFS rate at 5-years after randomization. |
|
3 months from radiotherapy.
The adverse events were reported according to the CTCAE 5.0 version.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | SBRT Group | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | CTCAE(5.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. SHI Changying | Shanghai Eastern Hepatobiliary Surgery Hospital | +86-021-81887735 | nona-peach@hotmail.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 1, 2015 | Jul 15, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 1, 2015 | Jul 15, 2021 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Aug 1, 2015 | Jul 15, 2021 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| D016634 | Radiosurgery |
| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D013238 | Stereotaxic Techniques |
| D019635 | Neurosurgical Procedures |
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Adjuvant SBRT after surgery group vs. surgery alone group.
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Participants in surgery alone group will not receive any adjuvant therapy after surgery for hepatocellular carcinoma. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Hepatitis Virus | The participants with hepatitis virus were recoreded in the baseline characteristics. Difference between the two groups in hepatitis will be examed. | Number | Number of Participants With Hepatitis Vi |
|
|
|
| Secondary | Overall Survival (OS) Rate. | OS was defined as time interval from randomization to death. | Posted | Count of Participants | Participants | OS rate at 5-years from randomization. |
|
|
|
| Other Pre-specified | Number of Participants Occured Adverse Events(AE) | AE was defined as side effect related to the radiotherapy | Posted | Count of Participants | Participants | AE will be evaluated up to 3 months after radiotherapy in SBRT group |
|
|
|
| 0 |
| 38 |
| 0 |
| 38 |
| 12 |
| 38 |
| EG001 | Surgery Alone Group | Participants in surgery alone group will not receive any adjuvant therapy after surgery for hepatocellular carcinoma. | 0 | 38 | 0 | 38 | 0 | 38 |
| Abdominal distension | Gastrointestinal disorders | CTCAE(5.0) | Systematic Assessment |
|
| Dyspepsea | Gastrointestinal disorders | CTCAE(5.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE(5.0) | Systematic Assessment |
|
| Liver injury | Hepatobiliary disorders | CTCAE(5.0) | Systematic Assessment |
|
| Myelosuppression | Blood and lymphatic system disorders | CTCAE(5.0) | Systematic Assessment |
|
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| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
| D013514 |
| Surgical Procedures, Operative |
| D008919 | Investigative Techniques |