Clinical trial NCT03964064: I125 Seed Implantation vs Stereotactic Radiotherapy for Pancreatic Cancer
Official title: 3D-printing Template-assisted CT-guided I125 Seed Implantation and Stereotactic Radiotherapy for Locally Advanced Pancreatic Cancer:A Prospective Multicenter Cohort Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Pancreatic Cancer Non-resectable
Brachytherapy
Radiotherapy
Keywords: Pancreatic Cancer Non-resectable
I125 seed implantation
Stereotactic radiotherapy
Lead sponsor: Peking University Third Hospital
Sponsor class: OTHER
Collaborators: name: Beijing 302 Hospital
name: Guangxi Ruikang Hospital
name: Tengzhou Central People's 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 patients with locally advanced pancreatic cancer who received stereotactic radiotherapy or ct-guided radioactive 125I seed implantation in the multicenter of the research group from July 2019 to June 2021 were collected, as well as follow-up data.To evaluate the clinical efficacy of stereotactic radiotherapy and ct-guided 125I seed therapy with 3D printing template in pancreatic cancer;In addition, the local control rate and side effects of ct-guided radioactive 125I particles in the treatment of pancreatic cancer lesions were explored, and the efficacy and safety of different doses of stereotactic radiotherapy were determined.

Detailed description: 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 80-100 when the distance between the tumor and gastrointestinal tract was more than 5 mm (alpha/beta=10) and 60-80 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. CT-guided radioactive 125I seeds therapy with 3D printing template for pancreatic cancer 2.1 Preoperative planning 2.2 Design and fabrication of 3D-PNCT 2.3 125I seeds implantation: 3D-PNCT was placed on the surface of the patient's treatment area, and positioned with the help of the patient's outline features, laser lines, body surface positioning lines and template alignment reference lines.

The location of the template and the tumor is well repeated. If there are errors, the template should be adjusted in time. The insertion needle was percutaneously punctured to a predetermined depth through a template guide hole. During the puncture process, the puncture path was monitored by CT scanning and fine-tuned if necessary to avoid injuring nerves and blood vessels. Seeds implantation and CT scan were performed according to the preoperative plan to understand the distribution of seeds. During the operation, the implant needle should be added or reduced when necessary to ensure that the whole target area is adequately irradiated and the surrounding normal tissues are protected.

2.4 Postoperative dose assessment: CT scan was performed after operation, and the image was transmitted to BTPS for dose verification (Figure 3-4). The dosimetric parameters included tumor volume, D90, mPD, V100, V150 and V200.

After these treatments,to evaluate the clinical efficacy of stereotactic radiotherapy and ct-guided 125I seed therapy with 3D printing template in pancreatic cancer;In addition, the local control rate and side effects of ct-guided radioactive 125I particles in the treatment of pancreatic cancer lesions were explored, and the efficacy and safety of different doses of stereotactic radiotherapy were determined.

Eligibility criteria: Inclusion Criteria:

* Age: 18-80 years old;
* Pathologically diagnosed pancreatic cancer patients;Follow-up treatment is in accordance with the NCCN2019 guidelines for standard treatment.
* Clinical MDT discussion, for the unresectable locally advanced pancreatic cancer, AJCC version 8 pancreatic cancer stage T4N0M0

Arterial invasion:

The pancreatic head and neck tumor invasion of pancreas superior mesenteric artery exceed 180 °;More than 180 ° celiac tumor invasion;The tumor invaded the first jejunal branch of the superior mesenteric artery.The pancreatic body tail superior mesenteric artery or celiac tumor invasion more than 180 °;The tumor invaded the abdominal trunk and abdominal aorta.

Venous invasion:

Tumor invasion or embolization (tumor thrombus or thrombus) of the head and neck of the pancreas leads to unresectable superior mesenteric vein or portal vein reconstruction;The tumor invaded the proximal end jejunal drainage branch of most superior mesenteric veins.The invasion or embolization of a tumor in the tail of the pancreas (thrombus or thrombus) leads to the unresectable reconstruction of the superior mesenteric vein or portal vein.

* ECOG physical condition score: 0-1, Karnofsky score 60, able to withstand puncture;
* Expected survival 3 months;
* Good function of main organs, no severe hypertension, diabetes and heart disease.
* Signed informed consent;
* Has a good compliance, families agree to accept the survival follow-up.

Exclusion Criteria:

* Non-locally advanced pancreatic cancer.
* Participated in other drug clinical trials within four weeks;There was a history of bleeding, and any bleeding event with severe grade of CTCAE5.0 or above occurred within 4 weeks before screening;
* Screening of patients with known central nervous system metastasis or a history of central nervous system metastasis.
* Patients with hypertension who cannot obtain good control by single antihypertensive drug treatment (systolic blood pressure \>140mmHg, diastolic blood pressure \>90mmHg);Having a history of unstable angina pectoris;Patients newly diagnosed with angina within 3 months before screening or myocardial infarction within 6 months before screening;Arrhythmia (including QTcF: 450ms in male and 470ms in female) requires long-term use of anti-arrhythmia drugs and New York heart association grade II cardiac dysfunction;
* Long-term unhealed wounds or incomplete fracture healing;
* Imaging showed that the tumor had invaded important blood vessels or the researchers judged that the patient's tumor had a very high possibility to invade important blood vessels during the treatment and cause fatal bleeding;
* Coagulation function abnormalities, have bleeding tendency;Patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogues;The use of low-dose warfarin (1mg oral, once daily) or low-dose aspirin (no more than 100mg daily) for preventive purposes is permitted on the premise that the international standardized ratio of prothrombin time (INR) is 1.5;
* Screening for the occurrence of hyperactive/venous thrombosis events in the first 6 months, such as cerebrovascular accidents (including temporary ischemic attack), deep vein thrombosis (except for venous thrombosis caused by intravenous catheterization in the early stage of chemotherapy, which was determined by the researchers to have recovered) and pulmonary embolism, etc.
* Thyroid function was abnormal in the past and could not be kept within the normal range even in the case of drug treatment.
* Attending has a history of psychotropic drug abuse, and can't attend or has mental disorder;
* Always half a year after abdominal tumor lesion radiation;
* Immunodeficiency disease, or has other acquired, congenital immunodeficiency disease, or has a history of organ transplantation;
* Judgment according to the researchers, there is serious to endanger the safety of patients or patients completed the research associated with disease.

Primary outcomes:
measure: Overall survival (OS)
timeFrame: 3 years after the treatment
measure: Progression-free survival (PFS)
timeFrame: 3 years after the treatment
Secondary outcomes:
measure: Local control rate，LCR
timeFrame: 3 years after the treatment
measure: Pain score
timeFrame: 1 years after the treatment
measure: Qol: Quality of Life Score of Tumor Patients
timeFrame: 3 years after the treatment
measure: Adverse reactions
timeFrame: 1 years after the treatment
Other outcomes:
Locations:
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: Tengzhou
country: China
facility: Tengzhou Central People's Hospital
state: Shandong
Study officials:
affiliation: Peking University Third Hospital
name: Junjie Wang, Chairman
role: STUDY_CHAIR
affiliation: Peking University Third Hospital
name: Fei Xu
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing 302 Hospital
name: Xuezhang Duan, Director
role: STUDY_DIRECTOR
affiliation: Tengzhou Central People's Hospital
name: Kaixian Zhang, Director
role: STUDY_DIRECTOR
affiliation: Guangxi Ruikang Hospital
name: Zuping Lian, Director
role: STUDY_DIRECTOR
affiliation: Peking University Third Hospital
name: Zhe Ji
role: STUDY_DIRECTOR
affiliation: Beijing 302 Hospital
name: Jing Sun
role: STUDY_DIRECTOR
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