Clinical trial NCT03963726: Clinical Efficacy of Stereotactic Radiotherapy and Microwave Ablation for Liver Metastases From Colorectal Cancer.
Official title: Clinical Efficacy of Stereotactic Radiotherapy and Microwave Ablation for Liver Metastases From Colorectal Cancer: a Prospective Multicenter Cohort Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Radiotherapy
Microwave Ablation
Liver Metastases
Colorectal Cancer
Keywords: Radiotherapy
microwave ablation
Liver Metastases
Colorectal Cancer
Lead sponsor: Peking University Third Hospital
Sponsor class: OTHER
Collaborators: name: Beijing 302 Hospital
name: Tengzhou Central People's Hospital
name: Guangxi Ruikang Hospital
name: Hunan Aerospace Hospital
name: Beijing Ditan Hospital
First posted: 2019-05-28
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: non-randomized trial
Primary purpose: TREATMENT

Brief summary: Data of 100 colorectal cancer patients with liver metastases who received stereotactic radiotherapy of Cyberknife or microwave ablation in the multicenter of the research group from June 2019 to May 2021 were collected, as well as follow-up data.To evaluate the clinical efficacy of stereotactic radiotherapy and microwave ablation in liver metastases.In addition, the local control rate and side effects of stereotactic radiotherapy and microwave ablation in the treatment of liver metastases were explored, and the efficacy and safety of different doses of stereotactic radiotherapy were determined.

Detailed description: In the study，data of 100 colorectal cancer patients with liver metastases who received Cyberknife stereotactic radiotherapy or microwave ablation in the multi-center of the research group from June 2019 to May 2021 were collected, as well as follow-up data.

1. Radiation: Stereotactic Radiotherapy 1.1 Equipment: Accuray VSI Cyberknife stereotactic radiotherapy platform, simulated positioning CT machine, MR, positron emission computed tomography PET-CT, vacuum pad.

   1.2 Radiotherapy localization: CT, MRI and PETCT were used to simulate localization.

   1.3 Relevant Definitions of Tumor Targets CT, MRI, PET-CT fusion, combined with MRI location and PET-CT location image for sketching.

   To delineate target areas and organs at risk. GTV: Combining localization and fusion images to delineate the tumors seen PTV = GTV + 0-10mm Dangerous organs: The stomach, duodenum, jejunum, ileum, colon, spinal cord and esophagus were delineated on the base sequence of CT plain scan.

   The target area should be approved by at least one physician in charge or by a physician in charge.

   1.4 Target volume radiation dose: According to the volume, location, organ function and other factors, the dosage of radiotherapy was determined. The range of BED value of radiotherapy was 90-120 when the distance between the tumor and gastrointestinal tract was more than 5 mm (alpha/beta=10) and 70-90 when the distance between the tumor and gastrointestinal tract was less than 5 mm (alpha/beta=10).

   1.5 Normal Tissue Limit: Reference to TG101 Report
2. Microwave ablation 2.1 Preoperative positioning and planning: 2.1.1 Determine the fixing device: generally choose vacuum pad to fix 2.1.2 Choosing the right position: The principle is to choose the position that is easy to operate, taking into account the comfort and tolerance of patients.

2.1.3 CT scan 2.1.4 The range of tumors was determined by CT images. In principle, at the maximum level, the skin points corresponding to the vertical center of the tumor are the marker points of the locating needle. At the same time, the center of the tumor was taken as the origin point, and the longitudinal and transverse cross lines were drawn on the patient's body surface. Roughly delineate the range of tumors according to CT in body surface 2.2 Surgery and intraoperative optimization 2.2.1 Posture reduction and fixation of patients 2.2.2 Oxygen inhalation, ECG and blood pressure monitoring 2.2.3 Installation of 3D Printing Planar Coordinate Template Fixer 2.2.4 Routine disinfection, cave towel laying, local infiltration anesthesia, fixing 3D printing plane coordinate template according to the range of tumors determined by physical examination and preoperative plan, and adjusting the direction of plane template by protractor.

2.2.5 Puncture locating needle and puncture assistant fixing needle in 4 directions of tumor margin.

2.2.6The real-time CT 2.5mm image was imported into the navigation system, the puncture needle was marked, the puncture needle was simulated, and the resolution of the template was adjusted accurately.

2.2.7 Enhanced CT scan to determine the position and angle of template and pin accurately 2.2.8 Layer by layer puncture according to preoperative plan 2.2.9 After inserting the ablation antenna to the reserved position, scan CT again to confirm whether the puncture needle has reached the planned position. 2.2.10 Complete ablation of tumors as planned.

2.3Postoperative observation 2.3.1 With the assistance of the staff in the hospital, they will be transported back to the ward by flat car with their families.

2.3.2 Re-measurement of blood pressure and heart rate 2.3.3Observe whether there is bleeding or exudation at the puncture point after operation, and give hemostasis and pain relief if necessary.

To evaluate the clinical efficacy of stereotactic radiotherapy and microwave ablation in liver metastases after these treatment.In addition, the local control rate and side effects of stereotactic radiotherapy and microwave ablation in the treatment of liver metastases were explored, and the efficacy and safety of different doses of stereotactic radiotherapy were determined.

Eligibility criteria: Inclusion Criteria:

* The age was 18 to 80 years old.
* It was confirmed by pathology that the liver metastasis of colorectal cancer was less than or equal to 3 lesions, each lesion was less than 3 cm, and there was no invasion of vascular tumor thrombus and adjacent organs according to the discussion of MDT.
* The preoperative imaging evaluation of iatrogenic or / and personal factors can realize microwave ablation or radiosurgery SBRT to require.
* The primary lesion has been treated radical and has no evidence of recurrence, and there is no metastasis outside the liver.
* The physical status score of ECOG : 0 ≥ 1 or more than 60 KPS.
* Predicted survival time was more than 3 months.
* The main organ function can tolerate stereotactic radiotherapy / microwave ablation, liver function child-pugh A or B, no severe hypertension, diabetes and heart disease. That is, within 14 days of random examination, the relevant test indexes meet the following requirements:

  1. blood routine examination: i. Hemoglobin was more than 90 g /L (no blood transfusion); ii. Neutrophil count was more than 1.5x109/L; iii platelet count was more than 100x109/ L;
  2. biochemical examination: i. total cholerythrin-1.5-ultraln (upper limit of normal); ii. Blood-valley-pyruvic transaminase (ALT) or blood-glutamic-aspartate aminotransferase (AST), 2.5-hulled; iii. The clearance of endophytic muscle was 60 ml/ min (ckroft-gault formula);
  3. cardiac Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) was more than 50%;
  4. blood glucose control was less than 7.2 mmol/ L, non-fasting blood glucose was less than 10 mmol/L, and glycosylated hemoglobin was less than 7%.
* Sign informed consent form.
* Good compliance, family agreed to cooperate with follow-up.

Exclusion Criteria:

* Patients who are being treated with drugs and whose liver metastases are stable or relieved, and who have participated in clinical trials of other drugs within four weeks;
* There was a history of bleeding, and any serious bleeding events of 3 degrees or more in ctcae 5.0 occurred within 4 weeks before screening.
* Patients with known central nervous system metastasis or history of central nervous system metastasis before screening. For patients with suspected central nervous system metastasis, CT or MRI examination must be performed within 14 days before randomization to exclude central nervous system metastasis.
* Patients with high blood pressure and single step-down medications were not able to obtain good control (systolic blood pressure was more than 140 mmHg, diastolic blood pressure was more than 90 mmHg); patients with a history of unstable angina; a new diagnosis within 3 months before screening was an event of myocardial infarction within 6 months before or after screening; Arrhythmias (including QTCF: male,450 ms, female, 470ms) require long-term use of anti-arrhythmic drugs and the New York Heart Association rating of grade ii cardiac insufficiency;
* Long-term unhealed wounds or incomplete fractures,
* Imaging showed that the tumor had invaded the perivascular area of important vessels or was judged by researchers that the tumor was highly likely to invade important blood vessels during treatment, resulting in fatal massive bleeding.
* Patients with abnormal coagulation function and bleeding tendency (14 days before randomization must be satisfied:INR is within the normal range without anticoagulant); Patients treated with anticoagulant or vitamin k antagonists such as warfarin, heparin or its analogues; Low dose warfarin (1mg oral, once a day) or low dose aspirin (not exceeding 100 mg); per day) is allowed for prophylactic purposes on the premise that the international standardized ratio of prothrombin time (INR) was less than 1.5;
* Hyperarteriovenous thrombosis occurred within 6 months before screening, such as cerebrovascular accidents (including temporary ischemic seizures), Deep venous thrombosis (except where venous thrombosis caused by intravenous catheterization after pre-chemotherapy has been cured by researchers) and pulmonary embolism, etc.
* There was abnormal thyroid function in the past, and even in the case of drug treatment, thyroid function could not be maintained within the normal range;
* Having a history of psychotropic substance abuse and unable to give up or have mental disorders.
* Radiotherapy for abdominal tumors has been carried out in the past.
* Have a history of immunodeficiency, or suffer from other acquired, congenital immunodeficiency diseases, or have a history of organ transplantation.
* According to the researchers' judgment, there are serious diseases that endanger the safety of patients or affect the completion of the study.

Primary outcomes:
measure: Local control rate
timeFrame: 3 years after the treatment
measure: Objective response rate
timeFrame: 1 years after the treatment
measure: Disease control rate
timeFrame: 3 years after the treatment
measure: PFS
timeFrame: 3 years after the treatment
Secondary outcomes:
measure: Overall survival
timeFrame: 3 years after the treatment
measure: Side effects
timeFrame: 1 years after the treatment
measure: Quality of life score of tumor patients(0-60)
timeFrame: 3 years after the treatment
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Ditan Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Beijing
country: China
facility: The fifth medical center of PLA general hospital
state: Beijing
city: NanNing
country: China
facility: Guangxi ruikang hospital
state: Guangxi
city: Changsha
country: China
facility: Hunan Aerospace Hospital
state: Hunan
city: Tengzhou
country: China
facility: Tengzhou Central People's Hospital
state: Shandong
Study officials:
affiliation: Peking University Third Hospital
name: Junjie U Wang, MD
role: STUDY_CHAIR
affiliation: Peking University Third Hospital
name: Fei U Xu, M Med
role: STUDY_DIRECTOR
affiliation: Beijing 302 Hospital
name: Xuezhang Duan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tengzhou Central People's Hospital
name: Kaixian Zhang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Ditan Hospital
name: Wei Li, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing 302 Hospital
name: Hui Xie, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Guangxi Ruikang Hospital
name: Zuping Lian, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hunan Aerospace Hospital
name: Xian Xu, M Med
role: PRINCIPAL_INVESTIGATOR
affiliation: Peking University Third Hospital
name: Fuxin Guo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing 302 Hospital
name: Jing Sun, M Med
role: PRINCIPAL_INVESTIGATOR
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