Research Interest

Development of Image-Guided Radiotherapy Strategies

The aim of this work is to develop and assess methods of IGRT

Radiation therapy for prostate cancer currently treats the whole gland to a uniform dose, but technological advances allow accurate matching of dose to tumour target. Functional MR methods significantly improve the localisation of tumour tissue and the Cancer Research UK MR Unit (Dr DeSouza, Professor Leach) is evaluating dynamic contrast-enhanced pharmacokinetic data, diffusion weighted images, R2* BOLD mapping and spectroscopic data using an endorectal receiver coil at 3T. Tumour localisation will be validated by comparison with specially prepared whole-mount histopathology using methodology developed in the ICR.  

We shall develop and compare registration algorithms to link this functional MR data with T2 anatomical images and the planning CT scans. A planning study will be performed in 30 patients comparing whole prostate IMRT (dose 74Gy) with prostate RT to 70Gy with a boost to the dominant intraprostatic lesion (DIL-IMRT) of up to 90Gy in 35 fractions.

Effect of rectal disten sion on disease control in two trials of dose escalation.

We shall design a phase I study of DIL-IMRT using rigorous dose constraints recruiting initially a cohort of 15 men expanding to 54 to exclude a significant grade 2 toxicity rate and subsequently a pilot phase III trial comparing DIL-IMRT with standard IMRT therapy. Successful implementation of IMRT and DIL-IMRT are dependent on a high degree of treatment accuracy accounting for patient set up variability and inter and intra fraction prostate movement.

The study will be undertaken with appropriate on or offline tracking of gold grain fiducial markers or using the Calypso system. Methods of automatic identification of gold grains will be developed and the potential of MLC tracking explored. We will determine the potential effects of these systems on treatment accuracy and model a reduction in planning margins and effect on normal tissue DVH and NTCP.

A major cause of prostate movement is due to variations in rectal filling which may be responsible for treatment failure. This problem is being addressed by attempting to reduce variations in rectal filling.  We have designed the ProSpare device (patent pending) having a technology development agreement with Neen HealthCare. Features include a unique shape to follow rectal curvature, 'venting' to reduce gaseous rectal distension and prostate movement, a neck which 'locks' into position in the anal sphincter and fiducial markers. We aim to show ProSpare is patient acceptable, locates accurately with respect to gold grain intraprostatic fiducials and produces greater consistency of rectal-filling permitting margin reduction with rectal sparing.  

An initial study has shown ProSpare is well-tolerated, a minor re-design should improve location reproducibility and a further randomised assessment is planned. If successful, a phase III multicentre trial will be designed. A further option to explore would be to combine ProSpare with a Calypso Beacon transponder which would define anterior rectal wall position.  

ProSpare (initial design) and sagittal reconstruction of planning CT scan with device.

Additionally in the DIRECT study we are gaining detailed dietary history to individualise dietary/pharmacological interventions pre-radiotherapy with repeat CT-planning and cone-beam CT assessment to improve rectal consistency.

The Calypso 4-D Localization System (Calypso Medical Technologies, Seattle, WA) is designed to provide accurate, precise, objective, and continuous target localization during external-beam radiotherapy. The Calypso system consists of 'wireless', implanted Beacon transponders and a noncontact AC magnetic array.  

These transponders are glass encapsulated and can be administered via a 14-gauge needle, in the same fashion as gold-grain fiducial markers are inserted for prostate localization. One or more transponders are implanted before acquisition of a treatment-planning CT-scan and their location is determined relative to the isocenter.  

When the patient is to be positioned for radiotherapy, a magnetic source and receiver coil array is used to determine the transponder positions. The array is tracked in real-time relative to the isocenter through the use of an infrared optical tracking system that is calibrated to the machine isocenter.  

The array can then signal and detect the beacons and register their location to the treatment machine. The system display updates at a 10-Hz frequency and can be considered a ‘continuous’ tracking method. We took delivery of the system in 2010 and following on initial assessment of accuracy in collaboration with the manufacturer we plan to develop new applications for gating and tracking.