Synchrotron radiotherapy: towards a human clinical trial.

Abstract

OBJECTIVES: Synchrotron radiotherapy represents a radical departure from the radiobiological principles of conventional radiotherapy (CRT) and has the potential to address currently unmet clinical needs. 1,2 The aim of this project is to address the following areas requiring development and systematic data in order to conduct the first human clinical trial at the Australian Synchrotron: (1) safety and normal tissue toxicity, (2) dose-equivalence with CRT, and (3) treatment planning system (TPS). METHODS: For dose-equivalence and normal tissue toxicity studies, mice were irradiated using both CRT and synchrotron radiotherapy using a dose-escalation methodology. To validate a TPS for synchrotron radiotherapy, clinical treatment plans delivered using CRT were imported into a commercially available TPS (Eclipse™, Varian Medical Systems) and compared to plans for the same datasets generated for synchrotron radiotherapy. RESULTS: Dose-response curves and the TD50 (toxic dose for 50% of mice) for CRT and synchrotron radiotherapy were calculated for total body irradiations and partial body irradiations of the head, thorax and abdomen of mice. The maximum tolerated (safe) dose was also determined for each modality. In regard to treatment planning, synchrotron radiotherapy plans were comparable to CRT plans only for small or superficial target volumes. CONCLUSION: The data collected in this project is fundamental to the progression of synchrotron radiotherapy to clinical practice. The unified effort of a multidisciplinary team including radiotherapists, radiation oncologists and medical physicists, will be required to progress synchrotron radiotherapy from a pre-clinical animal studies to a human clinical trial.