Individualized Precise Radiotherapy With the Guidance of Radiosensitivity of Locally Advanced Cervical Cancer

Study Overview
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Brief Summary
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Cisplatin-based chemoradiation (CCRT) has been considered as the standard care for patients with locally advanced cervical cancer (LACC). Nevertheless, increasingly more radio-resistant tumors still recur. IMRT including Rapid-Arc have obvious advantage in the dose distribution and organ protection, and positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) and Comet analysis have good sensitivity for detecting sites and radiosensitivity of disease. These may be helpful to individualized CCRT of LACC. Three hundred LACC patients are enrolled in the study, who were with FIGO stages IB2-IVA and had no para-aortic lymphadenopathy (>10 mm) assessed by PET-CT or MRI. All the patients received definitive radiotherapy consisting of external beam whole pelvic RT and HDR-ICBT. The cumulative linear quadratic equivalent dose (EQD2) was 70-75Gy prescribed at point A. Cisplatin 30 mg/m2 weekly was administered concurrently for 5 courses. 2-4 cycles TP (Taxol 135 mg/m2, D1 and DDP 25 mg/m2, D1-3) regimen sequential chemotherapy were performed if complete response (CR) not achieved according to magnetic resonance imaging (MRI) or PET-CT after CCRT. Hypothesis of the study is that CCRT and sequential chemotherapy is safe. Based on FDG-PET/CT and Comet assay, higher doses can be safely delivered individually to accurate tumor volume, while the doses to bladder and rectum are relative low. Comet and FDG-PET/CT-guided IMRT including RapidArc may improve survival in terms of time to progression (TTP), progression-free survival (PFS) and overall survival (OS) and less treatment-related toxicity. The data will be observed and analyzed.

Detailed Description
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Cisplatin-based chemoradiation (CCRT) has been considered as the standard care for patients with locally advanced cervical cancer (LACC). Nevertheless, increasingly more radio-resistant tumors still recur. IMRT including Rapid-Arc have obvious advantage in the dose distribution and organ protection, and positron emission tomography (PET) with F-18 fluorodeoxyglucose (FDG) and Comet analysis have good sensitivity for detecting sites and radiosensitivity of disease. These may be helpful to individualized CCRT of LACC. IMRT including RapidArc could be considered as a treatment selection for LACC patients, and it aims to improve the degree of target coverage, to protect organ at risk (OARs) and healthy tissue sparing compared to other RT solutions and to reduce significantly the treatment time as to RapidArc. Several studies have indicated that FDG-PET/CT increases the accordance between biopsies and delineated tumor volume and has the potential to positively impact the course of treatment. The Comet assay is attractive as a potential clinical test of tumour radiosensitivity. During radiotherapy, accurately defining disease areas is critical to avoid unnecessary irradiation of normal tissue. Based on FDG-PET/CT and Comet assay, higher doses can be safely delivered individually to accurate tumor volume, while the doses to bladder and rectum are relative low. Three hundred LACC patients are enrolled in the study, who were with FIGO stages IB2-IVA and had no para-aortic lymphadenopathy (>10 mm) assessed by PET-CT or MRI. All the patients received definitive radiotherapy consisting of external beam whole pelvic RT and HDR-ICBT. The cumulative linear quadratic equivalent dose (EQD2) was 70-75Gy prescribed at point A. Cisplatin 30 mg/m2 weekly was administered concurrently for 5 courses. 2-4 cycles TP (Taxol 135 mg/m2, D1 and DDP 25 mg/m2, D1-3) regimen sequential chemotherapy were performed if complete response (CR) not achieved according to magnetic resonance imaging (MRI) or PET-CT after CCRT. Hypothesis of the study is that CCRT and sequential chemotherapy is safe. Comet and FDG-PET/CT-guided IMRT including RapidArc may improve survival in terms of time to progression (TTP), progression-free survival (PFS) and overall survival (OS) and less treatment-related toxicity. The data will be observed and analyzed.

Official Title
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Individualized Precise Radiotherapy With the Guidance of Radiosensitivity: A Study on the Clinical Management Model of Locally Advanced Cervical Cancer

Conditions
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Cervical Cancer

Intervention / Treatment
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* Biological: 18F-FDG PET/CT and Comet assay guide RapidArc
* Biological: 18F-FDG PET/CT and Comet assay guide IMRT
* Biological: RapidArc
* Biological: 7f-IMRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age : 18-70 years old; Histology or cytology confirmed cervical squamous cell carcinomas; 2009 FIGO stage includesⅠB2, ⅡA2, ⅡB-ⅣA; Performance status(PS): 0-1; Peripheral blood meet the following conditions: neutrophil count > 2.0 * 109/L, white blood cell count > 4.0 * 109/L, the platelet count > 100.0 * 109/L; Liver and kidney function meet the following conditions: bilirubin < 1.5 mg/dl, AST and ALT < 2 times the upper limit of normal serum creatinine < 1.5 mg/dl, creatinine clearance > 50 ml/min; Signed informed consent before treatment. Exclusion Criteria: There is no definite pathological diagnosis; Clinical or imaging examination revealed distant metastases; Pelvic had received radiotherapy; Patients can't attend the study because of the associated with other diseases; Patients can't sign the informed consent because of mental disorders, mental disorders; Uncontrolled active infection; No follow-up.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PET/CT and Comet assay guided IMRT<br>18F-FDG PET/CT and Comet assay guide IMRT Based on FDG-PET/CT and comet analysis, higher doses of irradiation can be delivered to low sensitivity tumor region, so as to achieve individualized treatment. | Biological: 18F-FDG PET/CT and Comet assay guide IMRT<br>* Based on FDG-PET/CT and comet analysis, higher doses of irradiation can be delivered to low sensitivity tumor region, so as to achieve individualized treatment.<br>|
| Active Comparator: PET/CT and Comet assay guided RapidArc<br>18F-FDG PET/CT and Comet assay guide RapidArc: 1.A Rapid-Arc plan for cancer of the cervix uteri improved the sparing of organs at risk (OARs) with uncompromised target coverage. 2.Based on FDG-PET/CT and comet analysis, higher doses of irradiation can be delivered to low sensitivity tumor region, so as to achieve individualized treatment. | Biological: 18F-FDG PET/CT and Comet assay guide RapidArc<br>* 1.A Rapid-Arc plan for cancer of the cervix uteri improved the sparing of organs at risk (OARs) with uncompromised target coverage. 2.Based on FDG-PET/CT and comet analysis, higher doses of irradiation can be delivered to low sensitivity tumor region, so as to achieve individualized treatment.<br>|
| Active Comparator: RapidArc<br>RapidArc: A maximum DR of 600 MU/min was set for comparing the 7f-IMRT treatment time. Two 360° coplanar arcs (one clockwise arc rotated from 181° to 179° and the other counter-clockwise arc rotated from 179° to 181°) sharing the same isocentre were used. | Biological: RapidArc<br>* RapidArc: A maximum DR of 600 MU/min was set for comparing the 7f-IMRT treatment time. Two 360° coplanar arcs (one clockwise arc rotated from 181° to 179° and the other counter-clockwise arc rotated from 179° to 181°) sharing the same isocentre were used.<br>|
| Sham Comparator: 7f-IMRT<br>seventy-five patients received IMRT. The 7f-IMRT gantry angles were 0°, 51°, 102°, 153°, 204°, 255° and 306°, with 20 intensity levels and a dose rate of 400 monitor units (MU)/min. Doses were delivered using the step-and-shoot method.Conventional fractionation was used in all patients for a total dose 45-50.4 Gy with 6 MV high-energy photons. | Biological: 7f-IMRT<br>* seventy-five patients received IMRT. The 7f-IMRT gantry angles were 0°, 51°, 102°, 153°, 204°, 255° and 306°, with 20 intensity levels and a dose rate of 400 monitor units (MU)/min. Doses were delivered using the step-and-shoot method.Conventional fractionation was used in all patients for a total dose 45-50.4 Gy with 6 MV high-energy photons.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Progression-Free-Survival | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Overall survival | 3 years | 
| TTP | Time to progression | 3years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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locally advanced cervical cancer; radiotherapy