Optimal Margin Evaluation of Online Adaptive Radiotherapy for Postoperative Treatment of Endometrial and Cervical Cancer

Study Overview
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Brief Summary
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Online adaptive radiotherapy has demonstrated to be feasible to reduce inter-fractional radiotherapy errors as it re-optimizes treatment plan every fraction. To investigate the extent and value of margin reduction，we conduct a prospective clinical trial to determine the optimal margin and toxicity of smaller margin.

Detailed Description
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This is a prospective phase II clinical trial with an anticipated total of more than 380 radiotherapy fractions of 15 patients to evaluate optimal margin of iterative cone-beam computed tomography（iCBCT） guided online adaptive radiotherapy （oART） for postoperative treatment of endometrial and cervical cancer. Postoperative endometrial and cervical cancer patients with following characteristics are included in the present study:（a）underwent radical surgery （b）no residual tumor at the resection margin by postoperative pathology（c）pathological findings indicate risk factors but no metastasis (d) adjuvant radiotherapy are prescribe (e)without evidence of para-aortic metastatic lymph nodes. Five patients （almost 125 fractions）treated with oART have the target volume contoured on pre-treatment iCBCTs and end-treatment iCBCTs. Anterior-posterior, lateral, and superior-inferior shifts were calculated and the average shift in all directions was calculated. A clinical target volume (CTV) to planing tumor volume (PTV) expansion is determined and verifies on a validation cohort of 10 patients (almost 250 fractions) treated with oART. Record acute toxicity from the start of treatment to 3 months after treatment.

Official Title
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A Prospective Study to Evaluate Optimal Margin of Iterative Cone-beam Computed Tomography Guided Online Adaptive Radiotherapy for Postoperative Treatment of Endometrial and Cervical Cancer

Conditions
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Uterine Cervical Neoplasm, Endometrial Neoplasms

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. Postoperative endometrial and cervical cancer patients with pathologically confirmed no residual tumor at the resection margin and no evidence of distant metastasis (FIGO stage IVB). Pathological findings indicate risk factors and adjuvant radiotherapy are prescribe. Karnofsky score ≥ 70. Subjects aged ≥ 18 years and ≤ 70 years. No evidence of para-aortic metastatic lymph nodes. No contraindications to CT scanning. Subjects must be able to cooperate in completing the entire study. 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: Subjects who have received prior pelvic radiotherapy. Subjects with other primary malignancies. Subjects with contraindications to radiotherapy, as determined by the investigators. 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. Active infection with fever. Active inflammatory bowel disease.

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
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. The CTV contours of the following areas: vaginal cuff, 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 45-50.4Gy is delivered to CTV with online adaptive radiotherapy. | Radiation: online adaptive radiotherapy<br>* CTV covers pelvis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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, total an average of six month | 
| A minimum PTV margin could encompass CTV | Expansions were applied to the pretreatment PTV to assess required minimum margin required to encompass the postreatment CTV. | Through study completion, toral an average of six month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety for treatment as assessed by organs at risk doses | Safety for treatment was mainly evaluated by the organs at risk doses, including bladder, rectum, bone marrow, etc | Through study completion, total an average of six month | 
| Number of participants with acute toxicity as assessed by CTCAE 5.0 | Evaluated with CTCAE 5.0 | From the start of treatment to 3 months after treatment | 
| Adaptive time data | For each treatment in each fraction, adaptive time was recorded from first cone beam computed tomography (CBCT) to the selection of the preferred plan for the treatment. | Through study completion, total an average of six month | 
| Target 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, total an average of six month | 
| Organs at risk contouring accuracy | For every organs at risk in each fraction, the evaluation of accuracy for organs at risk contouring are categorized as follows: no edits, minor edits, moderate edits, major edits and not applicable. | Through study completion, total an average of six month | 
| Late toxicity evaluated with Radiation Therapy Oncology Group (RTOG)/EORTC late radiation morbidity scoring scheme | Evaluated every three months with Radiation Therapy Oncology Group (RTOG)/EORTC late radiation morbidity scoring scheme | total an average of 2-year | 

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