Doctor of Philosophy
Department of Physics
Wallace, Steven A., Treatment planning for boron neutron capture therapy for cancer, Doctor of Philosophy thesis, Department of Physics, University of Wollongong, 1996. http://ro.uow.edu.au/theses/1641
Over the past 40 years, tremendous advances in science and technology have been reflected in the techniques for diagnosis and therapy of cancer.
With such an enormous use of resources, we should realistically expect a reduction in incidence and mortality rates. While this is true for some types of cancers, the same cannot be said for the overall profile of mortality due to cancer. Indeed an increase in incidence and mortality from primary brain cancer in the elderly has been reported in the U S A and Europe. Clearly what must be recognised is that a significant shift in the research of today must be undertaken if these trends are to be altered in the future. From a fundamental level, conventional radiotherapy cannot effectively treat high grade brain tumours. Dose is preferentially delivered to the clinical tumour region via geometrically overlapping x-ray beams. This extrinsic selectivity relies on prior identification of the tumour site. This simply is not possible for sub-clinical metastases commonly associated with high grade brain tumours. What is required is a treatment technique with intrinsic selectivity that requires no prior identification of cancerous regions. The binary treatment modality Boron Neutron Capture Therapy (BNCT) currently offers the best prospects for intrinsic selectivity. This has been reinforced with recent research showing selective boron compound uptake in nests of as few as three cancer cells.
This project first details the construction of anthropomorphic head and torso phantoms suitable for use with neutron radiation. Tissues simulated include brain, liver, muscle, heart, lungs, stomach, intestines, pancreas, spleen, kidney and adipose. These phantoms were used to validate M C NP treatment planning calculations targeting the brain and liver using a variable voxel geometric reconstruction directly from "patient" C T scans. The user may specify "regions of interest" where small voxels may be applied giving detailed geometrical modelling and dose planning. Larger voxels may be applied to surrounding regions where detailed modelling is not required. Body tissues are discriminated on the C T scan on the basis of grayscale number. Programs are presented to enable the discrimination of spatially isolated tissues with common grayscale numbers.
MCNP calculations were initially benchmarked against the Petten HFR epithermal neutron beam using the geometrically simple cylindrical phantom. Epithermal neutron beam facilities are not available in Australia and the Petten facility is unique to Europe and one of the few in the world.
Gold and copper foil activation measurements generally show agreement to within 10 % of the calculations. Larger discrepancies with the cadmium covered manganese foils are possibly the result of a number of causes.
The results of the experimental Positive Intrinsic Negative (PIN) diode (responding dominanfly to fast neutrons) showed good agreement with the calculated response. Similarly Metal Oxide Semiconductor Field Effect Transistor (MOSFET) gamma detectors showed excellent correlation with the induced gamma dose. (The author's role in the PIN and M O S F ET detectors is limited to calculations of predicted response)
The prototype "patients" modelled from CT scans using the variable voxel technique include: i) the head phantom, ii) the torso phantom, and iii) the cervical region using C T scans of a cervical cancer patient. For the head and torso phantoms, M C N P calculations show agreement generally to within 10 % of bare and cadmium covered gold foil measurements in the brain, liver, lungs and pancreas irradiated in the Petten H F R epithermal neutron beam. PIN diode measurements are aJso well correlated to M C NP predicted resuKs, however there is evidence of increasing discrepancy with depth from the beam entrance surface of the phantoms. M O S F E T response also appears to be well correlated with gamma dose in the phantoms.
Further study is being undertaken to fully characterise the response of these detectors and eliminate spurious results before clinical application will be considered. These are possibly the most stringent tests of Monte Carlo modelling to date for epithermal neutrons.
Flux and dose calculations for the head and torso phantoms are superimposed upon C T scans, illustrating the latest software in three dimensional medical image visualization. Calculations are also displayed in a similar manner for the hypothetical 2S2Cf brachytherapy for cervical cancer treatment plan. These results indicate that the potential for boron neutron capture dose enhancement using 252Cf brachytherapy for cervical cancer is limited to very bulky tumours.
MCNP was also used with an ellipsoidal head model to examine the effect on treatment planning figures of merit of, i) boron ratios and concentrations, and ii) heavy water uptake. For a fixed tumour to blood boron ratio, little benefit is gained by increasing the blood boron level once the boron dose component dominates the healthy tissue dose. This limit is dependent upon the compound in use, or more precisely its pharmacokinetics and associated "compound factor". The effect of incorporating heavy water in brain tissues to improve B N C T efficacy is also examined. For bilateral irradiation with the Petten H F R beam, deuteration below toxicity limits provides an increase of approximately 2 0 % in the therapeutic ratio throughout the midbrain region.