Sivabalasingham, S; (2016) Biological and Clinical Evaluation of Intensity Modulated Radiotherapy for Brain Tumours. Doctoral thesis , UCL (University College London).

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Abstract

Intensity modulated radiotherapy has gained attention in recent years as a high precision radiation technique, allowing tumour dose escalation and reductions in high dose to adjacent normal organs. IMRT optimises the therapeutic ratio even further than conventional conformal radiation techniques, providing effective dose for tumour control, whilst minimising side effects. Despite these potential benefits, there is concern regarding long term effects from the associated low dose bath, exposing more normal tissue to lower radiation dose as compared to more conventional radiation techniques. However, the effects of this low dose radiation have yet to be established. In this thesis, y-H2AX was used to assess radiation-induced DNA damage within peripheral blood lymphocytes of patients undergoing fixed gantry or static field IMRT (SF-IMRT). The reproducibility and sensitivity of y-H2AX as a comparison of DNA damage following differing radiation techniques has been documented, with significant differences in y-H2AX foci seen following SF-IMRT in comparison to volumetric arc-IMRT and 3D conformal radiation. Efforts have been made to demonstrate a difference in whole body exposure from these techniques and variations in y-H2AX foci distributions seen following techniques may reflect greater whole body exposure following SF-IMRT, which may have impact on long term toxicity. The benefits of IMRT to treat complex shaped meningiomas, often located close to critical dose limiting structures, have been investigated in a clinical phase I/II study. The feasibility of using IMRT to deliver conformal radiation to meningiomas, whilst respecting normal tissue tolerance has been demonstrated here. The preliminary report from this ongoing clinical study documents effective, safe treatment with acceptable toxicity levels and comparable local control, particularly within grade I meningiomas. Prospective data collection has revealed improvements in neurological symptoms and no significant quality of life deterioration. The findings in this thesis provide further information to guide future work, examining the biological and clinical long term effects of new radiation techniques.

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