Adaptive Radiotherapy Using Plan Selection for Bladder Cancer

Study Overview
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Brief Summary
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This protocol describes a Phase 2 clinical trial of online adaptive Radiotherapy, using a library of 3 dose plans corresponding to Small, Medium and Large size bladder. The procedure includes 'Common Toxicity Criteria for Adverse Effects'(CTCAE) for registration of adverse effects (baseline, every 2'nd week during RT, 2 weeks, 3, 6, 12 and 24 month after RT) as well as cineMR for intra-fractional motion (baseline and every week during RT). Patients receive standard non-adaptive RT in the first week. Delineations of the bladder on the Cone-Beam scans (CBCT) from first week of treatment are used for planning the Small and Medium size bladder plans. Large size plan are the standard non-adaptive treatment plan used for the first week of treatment. A margin of 5 mm for intra fractional movement is used.

Detailed Description
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After inclusion patients are asked about their adverse effects by an oncologist using CTCAE (version 4.0) questionnaire. A planning CT-scan is acquired and for the first 10 patients also a MR-scan for intra fractional motion is acquired. The MR sequence is repeated every week during radiotherapy. The first week of treatment a standard non-adaptive IMRT-plan is used and CBCT-scans are acquired before and after treatment. The CBCT-scans are used for delineation of the bladder on the CBCT-scans from the first 4 fractions. The adaptive plans are generated from the union of the first 4 CBCT-bladders and the planning CT bladder (medium size) and the volume contained in at least 2 out of the 5 bladder volumes (small size). Details can be found in the reference list. From the 6'Th fraction the treatment is performed using the most appropriate size of treatment plan. CTCAE is repeated every other week during radiotherapy and 2 weeks, 3, 6, 12 and 24 month after radiotherapy.

Official Title
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Adaptive Radiotherapy Using Plan Selection for Bladder Cancer: A Phase II Trial

Conditions
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Adverse Effects for Adaptive RT of Bladder Cancer

Intervention / Treatment
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* Radiation: Adaptive Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven bladder cancer Age over 18 years Urothelial or planocellular carcinoma Stage T2 T4A Stage N0M0 Suitable for radiotherapy ECOG/WHO performance status 0-2 Exclusion Criteria: Suspected or confirmed distant metastases Previous surgery in the small pelvis Inflammatory bowel disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
Interventional Model Description: Daily adaptation of radiotherapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ART<br>Online adaptive radiotherapy | Radiation: Adaptive Radiotherapy<br>* CTCAE scoring baseline, every 2'nd week during RT, 2 weeks, 3, 12 and 24 month after RT cineMR (time resolved MR) baseline and weekly during RT for intra fractional motion<br>* Other names: Online Adaptive RT using plan selection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastro- Intestinal toxicity | Grade 2 or more GI toxicity using CTCAE 4.0 baseline, every 2'nd week during RT, 2 weeks, 3, 12 and 24 month after RT | Up to 2 years after ART | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intra-fractional changes of bladder shape and size | CineMR (time resolved MR) is performed pre-treatment and weekly during RT for the first 10 patients | spring 2013 | 
| Difference in accumulated dose to normal tissue | The gain of normal tissue sparring will be calculated using dose accumulation | autum 2014 | 
| 1 or 2 years disease free survival | 1 or 2 years disease free survival will be calculated | 2015 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adaptive radiotherapy, Bladder cancer