Use of Monte Carlo computation in benchmarking radiotherapy treatment planning system algorithms.

Radiotherapy treatments are becoming more complex, often requiring the dose to be calculated in three dimensions and sometimes involving the application of non-coplanar beams. The ability of treatment planning systems to accurately calculate dose under a range of these and other irradiation conditions requires evaluation. Practical assessment of such arrangements can be problematical, especially when a heterogeneous medium is used. This work describes the use of Monte Carlo computation as a benchmarking tool to assess the dose distribution of external photon beam plans obtained in a simple heterogeneous phantom by several commercially available 3D and 2D treatment planning system algorithms. For comparison, practical measurements were undertaken using film dosimetry. The dose distributions were calculated for a variety of irradiation conditions designed to show the effects of surface obliquity, inhomogeneities and missing tissue above tangential beams. The results show maximum dose differences of 47% between some planning algorithms and film at a point 1 mm below a tangentially irradiated surface. Overall, the dose distribution obtained from film was most faithfully reproduced by the Monte Carlo N-Particle results illustrating the potential of Monte Carlo computation in evaluating treatment planning system algorithms.

Assessment of background hydrogen by the Monte Carlo computer code MCNP-4A during measurements of total body nitrogen.

The use of a hydrogen internal standard to enable the estimation of absolute mass during measurement of total body nitrogen by in vivo neutron activation is an established technique. Central to the technique is a determination of the H prompt gamma ray counts arising from the subject. In practice, interference counts from other sources--e.g., neutron shielding--are included. This study reports use of the Monte Carlo computer code, MCNP-4A, to investigate the interference counts arising from shielding both with and without a phantom containing a urea solution. Over a range of phantom size (depth 5 to 30 cm, width 20 to 40 cm), the counts arising from shielding increased by between 4% and 32% compared with the counts without a phantom. For any given depth, the counts increased approximately linearly with width. For any given width, there was little increase for depths exceeding 15 centimeters. The shielding counts comprised between 15% and 26% of those arising from the urea phantom. These results, although specific to the Swansea apparatus, suggest that extraneous hydrogen counts can be considerable and depend strongly on the subject's size.

In vivo measurement of platinum in the kidneys using X-ray fluorescence.

A noninvasive in vivo method has been developed and optimized for measuring platinum concentrations in the kidneys of patients receiving chemotherapy. The method is based on polarizing the X-ray beam from an orthovoltage radiotherapy treatment unit, the Pantak DXT-300, and using the beam to produce emission of the characteristic platinum X-rays from the kidney. The platinum is derived from platinum-based chemotherapy drugs, such as cisplatin and its analogues (carboplatin and iproplatin), used to treat cancer patients. The clinical motivation for measuring the platinum concentration in both the kidneys and the tumor is to optimize the treatment by establishing the relationships between the accumulation of the drug at those sites. Such clinical information could be valuable in maximizing the therapeutic ratio toward the tumor tissue and limiting the hazards to the kidney. The performance of the system was experimentally optimized with respect to the applied X-ray tube voltage, filter material, and polarizer. Additionally, the MCNP-4B Monte-Carlo computer code was used to estimate the optimum shielding materials, the thickness surrounding the X-ray tube, and the arrangement of collimators, to protect patients from the hazards of the scattering radiation. Clinical measurements can be made with a combination of a bilayer of copper and silicon as polarizer, a 0.25-mm tin filter introduced in the path between the X-ray beam and the polarizer, and an operating voltage of 220 kV. The minimum detection limit achieved with this arrangement is 16 ppm, for a kidney depth of 3 x 3 cm, with a skin dose of 1.6 mGy and measurement time of 2,000 seconds.

An MCNP-based model of a linear accelerator x-ray beam.

The Monte Carlo N-Particle radiation transport computer code (MCNP) has been employed on a personal computer to develop a simple model simulating the major components within the beam path of a linear accelerator radiation head, namely the electron target, primary conical collimator, beam flattening filter, wedge filter and the secondary collimators. The model was initially used to calculate the energy spectra and angular distributions of the x-ray beam for the Philips SL 75/5 linear accelerator, in a plane immediately beneath the flattening filter. These data were subsequently used as a 'source' of x-rays at the target position, to assess the emergent beam from the secondary collimators. The depth dose distributions and dose profiles at constant depth for various field sizes have been calculated for a nominal operating potential of 4 MV and found to be within acceptable limits. It is concluded that the technique may be used to calculate the energy spectra of any linear accelerator upon specification of the component dimensions, materials and nominal accelerating potential. It is anticipated that this work will serve as the basis of a quality control tool for linear accelerators and treatment planning systems.

Plane polarized x-ray fluorescence system for the in vivo measurement of platinum in head and neck tumours.

A plane polarized x-ray fluorescence system based on an orthovoltage radiotherapy treatment unit, the Pantak DXT-300, has been developed and optimized to measure tumour platinum concentration. The platinum derives from platinum based chemotherapy agents, such as cisplatin and carboplatin used to treat tumours in the head and neck region. Photons from an x-ray tube are polarized by scattering through 90 degrees, and used to stimulate the emission of characteristic platinum x-rays from the tumour. Information about the drug in the tumour could be of use in establishing dose-response relationships, in order to optimize the treatment and reduce the toxicity of the drug. The performance of the system was optimized with respect to the applied x-ray tube voltage, the current and the filter material; the effect on the minimum detection limit (MDL) of the thickness of the overlying tissue surrounding the tumour was investigated in detail. The lowest MDL is achieved using 0.25 mm of tin filter and x-ray tube voltage of 220 kV. This is 5.6 ppm for a tumour surrounded with 20 mm of overlying tissue, a measurement time of 2000 s and an estimated skin dose of 3.0 mGy. This represents the most sensitive in vivo XRF system to date. We have embarked on a clinical pilot study to measure the platinum concentration in tumours of the head and neck, and expect initial results to be available in the near future.

Changes in body fat: measurements by neutron activation, densitometry and dual energy X-ray absorptiometry.

The measurement of body fat in ten subjects (BMI from 22 to 43 kg/m2), and in particular the changes arising from a ketogenic diet, by the techniques of in vivo neutron activation analysis (NAA), densitometry (using two- and four-compartment models) by under water weighing (UWW) and dual energy X-ray absorptiometry (DXA) was compared. The association between techniques for the fat changes was generally high (r = 0.70 to 0.98) and significant (p < 0.05). Assessment of agreement between DXA and the other techniques revealed discrepancies with significant slope and high association (r = -0.81 and -0.64). Whilst NAA and UWW appeared to measure similar changes, DXA underestimated small changes.

Monte Carlo simulation of prompt gamma neutron activation analysis using MCNP code.

Prompt gamma neutron activation analysis (PGNAA) is the most direct method of measuring total-body nitrogen. In combination with internal hydrogen standardisation, it is possible to reduce the dependence on body habitus. The uniformity of activation and detection, however, cannot be optimised sufficiently to eliminate the dependence entirely, and so further corrections are essential. The availability of the powerful Monte Carlo code MCNP(4A) has allowed a more accurate analysis of the activation facility, and yields corrections for body habitus and superficial fat layers. The accuracy of the correction is retained as the source-to-skin distance is reduced, although the activation uniformity is thereby degraded. This allows the use of a 252Cf source with lower activity and hence reduces the running cost of the facility.

Body composition measurements using DXA and other techniques in tamoxifen-treated patients.

Tamoxifen is an anti-oestrogenic drug which is widely used in the treatment of patients with breast cancer. There is increasing interest in using the drug both for benign breast disease and as a chemo-preventative agent of the drug in women at high risk of breast cancer. Despite the fact that the acute side-effects of the drug are few, its agonistic and antagonistic oestrogenic effects are not fully known and may have some undesirable effects for patients treated with the drug for several years. A number of studies carried out recently indicate a varying degree of change in bone mineral content following treatment with tamoxifen. These studies concentrated mainly on bone mineral density measurements only and non of them reported the effects of tamoxifen on lean body mass and fat mass. In this study we measured lean body mass and fat mass in tamoxifen-treated females and a comparison group to determine the difference between the two groups. Twenty-six women receiving tamoxifen (20 mg/d) have participated in this study. The control group comprised 31 healthy women of a similar age. Total body bone mineral (TBBM) was measured using a dual-energy X-ray absorptiometry (DXA) (Hologic INV., Waltham, U.S.A.). Similarly, regional and total body soft tissue (lean and fat tissue) were measured using the DXA system. In addition to DXA measurements, percentage body fat (%BF) was measured using total body potassium counting (TBK), skinfold anthropometry (SF), infrared interactance (i.r.) and bioelectric impedance analysis (BIA). Results from DXA alone showed that there were no significant differences between the two groups for TBBM, regional and total body lean tissue mass. However, there was a significant difference between the two groups (P < 0.05) for %BF measurement. Similarly there was a significant difference between the two groups (P < 0.05) for %BF measured by other body composition techniques. Although there is no other research reported on the effects of tamoxifen on %BF, this retrospective study indicates that tamoxifen may lead to increase in fact content in women who are subjected to this treatment. We conclude that this observation is probably related to the agonistic oestrogenic effect of Tamoxifen on body fat. To our knowledge this deleterious effect has not been reported before and it should be taken into considerable when comprising different types of anti-oestrogenic drugs. Furthermore, patients should be warned about this side-effect when they are prescribed Tamoxifen therapy.

Optimisation of a polarised X-ray source for the in vivo measurement of platinum in head and neck tumours.

There is a continuing need to improve the understanding of kinetics of platinum-based chemotherapeutic agents, such as cisplatin and paraplatin. Although these agents demonstrate highly effective anti-cancer activity, they also have associated, often dose-limiting, side-effects such as nephrotoxocity. In vivo X-ray fluorescence (XRF) has been proven to be a suitable technique for measuring the uptake of these agents in tumour and critical organs, but radioisotope based systems have not found their way into routine clinical use due to their rapid increase in minimum detection limit (MDL) with depth. Polarised X-rays offer a solution to this problem by reducing the scattered background, which not only reduces the MDL, but also allows the intensity of the source to be increased without saturating the detector electronics. This paper describes the development and optimisation of a polarised XRF system for in vivo measurement of platinum in head and neck tumours, whose response to cisplatin is often unpredictable. The polarised X-ray source comprises a clinical X-ray therapy unit (the Pantak DXT-300) with removable purpose-built collimators. Optimisation studies have concentrated upon the operating voltage, polariser material and additional filtering. The optimum voltage was found to lie within the range 200-300 kV for all polarising materials. There was no significant difference using copper, aluminium or iron as the polariser. Increasing the additional filtering improved the MDL for a preset number of counts, but decreased the count-rate significantly, resulting in unacceptably long counting times. An MDL of 9 ppm was achieved for a phantom depth of 2 cm, using a copper polariser, 0.25 mm of tin filtering and an operating voltage of 220 kV. TLD measurements showed that the corresponding skin dose was 6 mGy. These results indicate a factor of improvement in the MDL from the previous 99mTc system, for a factor of two lower skin dose. The detection limit achieved is the lowest reported to date, and is considered adequate for a comprehensive patient study. It is anticipated that this will yield better information and the pharmacokinetics of platinum compounds and will lead to optimisation of both chemo and radiotherapy treatment. Additionally this technique can be easily integrated into any radiotherapy based department.

The performance of an infra-red interactance instrument for assessing total body fat.

Infra-red interactance has been evaluated as a technique for measuring total body fat in comparison with a range of alternative methods. The alternative techniques employed were neutron activation analysis, tritiated water dilution, whole-body potassium-40 counting, skinfold anthropometry, bioelectrical impedance analysis and the body mass index. The study group consisted of 43 healthy adults (16 males and 27 females). For 11 women, measurements were obtained before and after 11 weeks on a very low-calorie diet, giving a total of 54 sets of data. Correlation coefficients between infra-red interactance and the other techniques varied between 0.58 (p < 0.0002) and 0.80 (p < 0.0001) for females, and between 0.64 (p < 0.009) and 0.94 (p < 0.0001) for males. The average fat for the study group was underestimated by 15% using infra-red interactance in comparison with the average fat obtained from the other techniques. It was also noted that the infra-red interactance instrument yielded a very narrow range of body fats in females in comparison with the other techniques. It is essential that these differences are reconciled before infra-red interactance takes a significant role in body composition analysis.

133Xe for the in vivo X-ray fluorescence measurement of platinum.

In vivo measurements of platinum are important for studying the pharmacokinetics of platinum-based cytotoxic drugs. The technique of in vivo X-ray fluorescence can be utilized for such measurements. The feasibility of using 133Xe in near-backscatter (almost 180 degrees ) geometry has been investigated and results compared to phantom measurements made using 99Tcm in the same experimental set-up. An improvement in minimum detection limits is observed for all phantom depths less than 25 mm.

Bone and soft tissue changes in paraplegic patients.

The loss of bone mineral in 66 paraplegic patients has been measured in the lower femoral shaft by scanning the leg with a beam of mono-energetic radiation from 241Am. The profile of the transmitted radiation was used to determine a parameter which was related to bone mass. The bone mass of paraplegic patients was significantly lower than normal. Persistent paralysis does not lead to a continued fall in bone mass, but once it has fallen, bone mass remains constant. Soft tissues also showed a muscle/fat ratio was lower than normal.

Changes in skeletal mineral in patients on prolonged maintenance dialysis.

The measurement of bone loss in patients undergoing maintenance dialysis over a period of two and a half years is reported. The tendency to lose bone is a likely event in renal failure, but depends more on the individual patient than on the type of dialysis used, provided that steps are taken to prevent avoidable calcium loss during dialysis. Vitamin D therapy was an important factor in preventing bone loss in some cases. The tendency to lose bone more readily when both kidneys were absent may have reflected a deficiency of 1-25 dihydrocholecalciferol. On the other hand, bone loss was also observed in transplanted patients. The need to measure bone loss at regular intervals once renal failure has been diagnosed is stressed.