Adaptive Radiotherapy Using Plan Selection for Bladder Cancer (plan selection)

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.

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.

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

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

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

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Vestergaard A, Hafeez S, Muren LP, Nill S, Hoyer M, Hansen VN, Gronborg C, Pedersen EM, Petersen JB, Huddart R, Oelfke U. The potential of MRI-guided online adaptive re-optimisation in radiotherapy of urinary bladder cancer. Radiother Oncol. 2016 Jan;118(1):154-9. doi: 10.1016/j.radonc.2015.11.003. Epub 2015 Nov 26.

Vestergaard A, Muren LP, Lindberg H, Jakobsen KL, Petersen JB, Elstrom UV, Agerbaek M, Hoyer M. Normal tissue sparing in a phase II trial on daily adaptive plan selection in radiotherapy for urinary bladder cancer. Acta Oncol. 2014 Aug;53(8):997-1004. doi: 10.3109/0284186X.2014.928419. Epub 2014 Jun 24.

Gronborg C, Vestergaard A, Hoyer M, Sohn M, Pedersen EM, Petersen JB, Agerbaek M, Muren LP. Intra-fractional bladder motion and margins in adaptive radiotherapy for urinary bladder cancer. Acta Oncol. 2015;54(9):1461-6. doi: 10.3109/0284186X.2015.1062138. Epub 2015 Aug 27.