Dose-escalated bladder radiotherapy: Result of first dose cohort


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Fiona McDonald1, Shaista Hafeez1,2, Susan Lallondrelle1, Victoria Harris1,2, Helen Taylor1, Karole Warren-Oseni1, Vibeke Hansen1, Kelly Jones1, Alan Thompson1, Vincent Khoo1, Robert Huddart1,2
1The Royal Marsden NHS Foundation Trust, Surrey, UK, 2The Institute of Cancer Research, Surrey, UK

Background

The purpose of this prospective phase I study was to assess the safety of dose escalation for localised muscle-invasive bladder carcinoma using image-guided adaptive radiotherapy (RT) combined with reduced high-dose tumour volume.

Method

Radical RT was planned and delivered in 3 phases. Phase 1 was delivered to the whole empty bladder (10Gy 5#). Bladder variation, assessed on daily imaging in phase 1, was used to decide on a composite volume or plan of the day approach for the adaptive phase 3. Phase 2 was delivered to a tumour boost volume in a partially full bladder (18Gy 9# if normal tissue dose-constraints were met, otherwise 14Gy 7#). Subsequently, the adaptive phase 3 was delivered to the whole empty bladder (40Gy 20#). The primary endpoint was late RTOG toxicity.

Results

Twenty patients were recruited between May 2009 and April 2011. Fourteen (70%) patients met the normal tissue constraints for reduced high-dose volume dose escalation. Nine patients (64%) had a composite volume selected for the phase 3 adaptive technique and 5 (36%) were treated using optimal plan of the day selection. At a median follow-up of 8 months, 10 of the dose escalated patients remain well with no sign of cancer recurrence and 4 patients have died of unrelated causes (2 from cardiac and 2 from pulmonary disease). There have been no grade ≥3 late toxicities. Three (21%) patients have experienced G1-2 late genitourinary toxicity.

Conclusion

Implementation of image-guided adaptive RT techniques with reduced high-dose volume strategy allow for a proportion of patients to achieve tumour dose-escalation within normal tissue constraints. Toxicity data to date suggest tolerability of 68Gy in the patients whose plans met normal tissue dose constraints. Local disease control rates are promising. According to protocol recruitment has now commenced at 72Gy dose level and follow-up continues.