Online Adaptive Radiotherapy Cervical Cancer With Reduced Margin for Cervical Cancer

Study Overview
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Brief Summary
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Online adaptive radiotherapy (oART) has demonstrated to be feasible to reduce planning target volume (PTV) margins for cervical cancer. To explore the value of reduced margins in oART for cervical cancer, we conducted a prospective clinical trial to determine the clinical efficacy and toxicity of reduced margins.

Detailed Description
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This is an investigator-initiated efficacious, single-center, open-label clinical trial study. This study hypothesizes that the use of reduced PTV margins in oART for cervical cancer could decrease toxicity and achieve more accurate dosimetric coverage. A dose of 50.4 Gy is delivered to clinical target volume (CTV) with reduced margin oART. Patients receive cisplatin based concurrent chemotherapy. The primary endpoint is acute toxicity.

Official Title
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A Prospective Study to Evaluate Online Adaptive Radiotherapy in Cervical Cancer With Reduced Margin

Conditions
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Uterine Cervical Neoplasm

Intervention / Treatment
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* Radiation: online adaptive radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be informed of the investigational nature of this study and give written informed consent before treatment. Age ≥18 years and ≤ 75 years. Patients with newly histologically confirmed cervical cancer, including squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma, et al. No evidence of para-aortic metastatic lymph nodes (MLNs) and inguinal lymph nodes on CT, MRI or positron emission tomograph (PET)/CT. No contraindications to CT scanning. No evidence of distant metastasis (FIGO stage IVB). Adequate marrow: neutrophile granulocyte count ≥1.5*10^9/L, hemoglobin ≥ 80 g/L, platelet count ≥100*10^9/L. Normal liver and kidney function: Creatinine (Cr) < 1.5 mg/dl, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) < 2*upper limit of normal (ULN). Exclusion Criteria: With common iliac MLNs. Tumor extended to the lower third of the vagina. Tumor spread to mucosa of the bladder or rectum. Prior surgery (including pelvic or para-aortic lymph nodes resection, except for tumor biopsy), radiotherapy or chemotherapy to primary tumor or nodes. Prior malignancy. History of previous radiotherapy to the abdomen or pelvis. Pregnancy or lactation. Active inflammatory bowel disease, or history of severe stomach or duodenal ulcer. Active infection with fever. Patients with unacceptable risk that intracavitary brachytherapy can not be conducted. Any severe disease which may bring unacceptable risk or affect the compliance of the trial, for example, unstable cardiac disease requiring treatment, renal disease, chronic hepatitis, diabetes with poor control, and emotional disturbance.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Online Adaptive Radiotherapy<br>Patients receive online adaptive radiotherapy with 5-10mm PTV margin. The CTV contours of the following areas: gross tumor volume (GTV), cervix (if not already encompassed by the GTV), uterus, parametria, ovaries, vaginal tissue, obturator nodal chain, internal iliac nodal chain, external iliac nodal chain, presacral nodal chain and common iliac nodal chain. The upper border of CTV is at the level of aortic bifurcation. A dose of 50.4Gy is delivered to CTV with online adaptive radiotherapy. | Radiation: online adaptive radiotherapy<br>* PTV with 5-10 margins covers CTV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient-reported acute toxicity | Patient-reported acute toxicity evaluated with European Organization for Research and Treatment of Cancer Quality of Life C30 (EORTC QLQ-C30) 3.0 questionnaire | From the start of treatment to 3 months after treatment | 
| Physician-reported acute toxicity | Physician-reported acute toxicity evaluated with Common Terminology Criteria for Adverse Events (CTCAE) 5.0 | From the start of treatment to 3 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Late toxicity evaluated with Radiation Therapy Oncology Group (RTOG)/EORTC late radiation morbidity scoring scheme | Evaluated with Radiation Therapy Oncology Group (RTOG)/EORTC late radiation morbidity scoring scheme | 2-year | 
| The irradiated doses of organs at risk | The organs at risk includes bladder, rectum, bone marrow, femur head left, femur head right and bowel that may be irradiated near the target volume | Through study completion, an average of eight month | 
| The dose coverage of target volume as assessed by planing tumor volume V100% | Planing tumor volume V100%, defined as the planing tumor volume receiving at least 100% of the prescribed dose (V100%), is used to evaluate the dose coverage of target volume. | Through study completion, an average of eight month | 
| Target volume contouring accuracy | For every target in each fraction, the evaluation of accuracy for target contouring are categorized as follow: no edits, minor edits, moderate edits, major edits and not applicable. | Through study completion, an average of eight month | 
| Response evaluation evaluated with RECIST 1.1 | Evaluated with RECIST 1.1 | One month after treatment | 
| Movement of the uterus during per radiotherapy fractions | The pre- and post-treatment CBCT scans will be obtained during per treatment. The uterus intra-fractional motion were evaluated by comparison of uterus centroid from pre-treatment CBCT and uterus centroid from post-treatment images. | Through study completion, an average of eight month | 
| Movement of the cervix during per radiotherapy fractions | The pre- and post-treatment CBCT scans will be obtained during per treatment. The cervix intra-fractional motion were evaluated by comparison of cervix centroid from pre-treatment CBCT and cervix centroid from post-treatment images. | Through study completion, an average of eight month | 
| Progression-free survival | Progression-free survival is defined as the time from randomization to disease progression or death from any cause, whichever is first. | 2-year | 
| Personalized margin for cervical cancer | Pre- and post-treatment images are uploaded to the online adaptive radiotherapy simulator to re-delineate the target volume and determine the personalized margin range. | Six month after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uterine Cervical Neoplasm, Online Adaptive Radiotherapy