The use of diode dosimetry in quality improvement of patient care in radiation therapy

The purpose of this work is to improve the quality of patient care in radiation therapy by implementing a comprehensive quality assurance (QA) program aiming to enhance patient in vivo dosimetry on a routine basis. The characteristics of two commercially available semi-conductor diode dosimetry systems were evaluated. The diodes were calibrated relative to an ionization chamber-electrometer system with calibrations traceable to the National Institute of Standards and Technology (NIST). Correction factors of clinical relevance were quantified to convert the diode readings into patient dose. The results of dose measurements on 6 patients undergoing external beam radiation therapy for carcinoma of the prostate on three different therapy units are presented. Field shaping during treatments was accomplished either by multileaf collimation or by cerrobend blocking. A deviation of less than +/-4% between the measured and prescribed patient doses was observed. The results indicate that the diodes exhibit excellent linearity, dose reproducibility, minimal anisotropy, and can be used with confidence for patient dose verification. Furthermore, diodes render real time verification of dose delivered to patients.     

Response analysis of TLD-300 dosimeters in heavy-particle beams

In vivo dosimetry is recommended as part of the quality control procedure for treatment verification in radiation therapy. Using thermoluminescence, such controls are planned in the p(65) + Be neutron and 85 MeV proton beams produced at the cyclotron at Louvain-La-Neuve and dedicated to therapy applications. A preliminary study of the peak 3 (150 degrees C) and peak 5 (250 degrees C) response of CaF2:Tm (TLD-300) to neutron and proton beams aimed to analyse the effect of different radiation qualities on the dosimetric behaviour of the detector irradiated in phantom. To broaden the range of investigation, the study was extended to an experimental 12C heavy ion beam (95 MeV/nucleon). The peak 3 and 5 sensitivities in the neutron beam, compared to 60Co, varied little with depth. A major change of peak 5 sensitivity was observed for samples positioned under five leaves of the multi-leaf collimator. While peak 3 sensitivity was constant with depth in the unmodulated proton beam, peak 5 sensitivity increased by 15%. Near the Bragg peak, peak 3 showed the highest decrease of sensitivity. In the modulated proton beam, the sensitivity values were not significantly smaller than those measured in the unmodulated beam far from the Bragg peak region. The ratio of the heights of peak 3 and peak 5 decreased by 70% from the 60Co reference radiation to the 12C heavy-ion beam. This parameter was strongly correlated with the change of radiation quality.     

Intention-to-treat vs. on-treatment analyses of clinical trial data: experience from a study of pyrimethamine in the primary prophylaxis of toxoplasmosis in HIV-infected patients. ANRS 005/ACTG 154 Trial Group

Major advances have recently been made in photodynamic therapy (PDT) for clinical application, including the development of more powerful photosensitizers and light sources and suitable light applicators. PDT is emerging as an attractive new form of cancer therapy, suitable for treating superficial lesions (less than 1 cm in depth) and carcinoma in situ, or as an adjuvant to surgery for more bulky disease. PDT is therefore complementary to radiotherapy which is better suited to treating larger tumours. There are some qualitative similarities between light distribution in tissue during superficial illumination and ionizing radiation dose distributions during external beam irradiation, or between interstitial PDT and brachytherapy, although the geometric scale is very different (visible light penetrates a maximum of 5-10 mm in tissue). The contribution of scattered light to tissue irradiance is much greater than for ionizing radiation and in situ light dosimetry is very important (although rather complicated) to ensure adequate illumination without over-treating. Dosimetry and treatment planning are highly advanced for ionizing radiation and are routine in all radiotherapy departments. Proper in situ light dosimetry and dose distribution calculation for PDT is in its infancy. Physicists have an important role to play in the further optimization of clinical PDT and much of the infrastructure and expertise present in the radiotherapy department is ideally suited to accommodate PDT. In this review, parallels and contrasts are made between PDT and ionizing radiation for both mechanistic and dosimetric aspects of the therapies. A summary of the most interesting clinical applications is also given.     

Arterial oxygen saturation over time and sleep studies in quadriplegic patients

Therapeutic nuclear medicine is rapidly developing as an additional treatment modality in oncology. Its unique characteristics are the systemic, yet selective delivery of radiation doses in target tissues, its non-invasiveness, the relative lack of immediate and late side effects, and the advantage that uptake and retention in the tumor can be pre-assessed by tracer studies. Many different tumor seeking radiopharmaceuticals are being used for therapy by different routes and a variety of targeting mechanisms. The current clinical role of radionuclide therapy is briefly reviewed, as well as more general aspects and considerations, such as mechanisms for tumor targeting, the choice of radionuclide labels, radiopharmacy, drug delivery, radiation protection, dosimetry and toxicity.     

Direct determination of kerma for a d(48.5) + Be therapy beam

An experimental determination of the neutron kerma ratio between muscle tissue and A-150 plastic was performed at the newly commissioned d(48.5)+ Be therapy facility in Detroit. Low-pressure proportional counters with separate walls made from A-150 plastic, graphite, zirconium oxide and zirconium served to measure ionization yield spectra. The absorbed dose in the wall of each counter was determined and rendered the A-150 and carbon kerma directly, whilst that for oxygen was deduced from differences between the matched metal oxide and metal pair. This enabled the evaluation of an effective kerma ratio as a function of radiation field size and hydrogenous filtration. Although filtration was observed to harden the beam, the application of a single kerma ratio for the various irradiation conditions investigated was found to be appropriate. A neutron kerma ratio of 0.90+/-0.03 was assessed for the Detroit facility, which is lower at the 1sigma level than the 0.95 currently recommended in the dosimetry protocol for high-energy neutron beams.     

Comparison of effectiveness of thermoluminescent crystals LiF:Mg,Ti, and LiF:Mg,Cu,P for clinical dosimetry

This study compared the relative effectiveness of TLD crystals LiF:Mg,Ti (TLD-100) and LiF:Mg,Cu,P (TLD-700H) for clinical dosimetry, focusing on reproducibility, linearity, and energy response. Experimental results indicated that TLD-700H was superior to TLD-100 with regard to reproducibility, lack of supralinearity, and the absence of variation in TL signal with radiation quality. TLD-700H also had the additional advantages of higher sensitivity and immediate readability. The investigators conclude that this relatively new TLD crystal shows promising potential for clinical dosimetry.     

A proposal for minimum detectable compartment in MIRD dosimetry modelling

The accuracy of radiation dose estimates from radiopharmaceutical administrations has recently become more important for three main reasons: (i) clinical providers are demanding more information on diagnostic procedures; (ii) regulatory groups are scrutinizing dosimetry for research subjects; and (iii) accurate organ doses are crucial in therapeutic administrations. These dose estimates are a sensitive function of the residence times. Because most clinical data acquisition protocols are limited to the first 24 h after dose administration, the area under the remainder of the time-activity curve (TAC) must be estimated. Estimation methods range from assuming physical decay only (overly conservative) to extrapolating end point physiological kinetics (overly liberal). This study demonstrates how much the results from these two methods vary and develops an alternative method which more accurately estimates this remainder term. A method, called the minimum detectable compartment (MDC), is constructed so that an accurate dose estimate can be made with a realistic measure of the remainder term. The method for determining MDC uses standard hypothesis testing. Using an analogue of the traditional minimal detectable activity calculation, a model with and without constant compartments is fitted to the TAC. The size of the constant compartment is varied until the relative likelihood of the two models meets the desired measure of power and sensitivity. Computer simulations of a simple mono-exponential are used to demonstrate the MDC as a function of the model, the number of data points, the range of the data and the noise in the data. The MDC is a very sensitive function of the data range. It falls by more than 50% when the data range is increased from two to three half-lives. In addition, the MDC is moderately sensitive to the noise in the data and relatively insensitive to the number of data points. These findings suggest that the MDC method can also be uses a priori to indicate what type of data collection regimen is necessary to achieve a certain accuracy.     

Radiance modelling using the P3 approximation

Light dosimetry is an essential component of effective photodynamic therapy (PDT) of tumours. Present PDT light dosimetry techniques rely on fluence-based models and measurements. However, in a previous paper by Barajas et al, radiance-based light dosimetry was explored as an alternative approach. Although successful in demonstrating the use of Monte Carlo (MC) simulations of radiance in tissue optical characterization, the MC proved time consuming and impractical for clinical applications. It was proposed that an analytical solution to the transport equation for radiance would be desirable as this would facilitate and increase the speed of tissue characterization. It has been found that the P3 approximation is one such potential solution. Radiance and fluence expressions based on the P3 approximation were used to optically characterize an Intralipid-based tissue phantom of varying concentration of scatterer (Intralipid) and absorber (methylene blue) using a plane wave illuminated, semi-infinite medium geometry. The results obtained compare favourably with the Grosjean approximation of fluence (a modified diffusion theory) using the same optical parameters (mu(a), mu(s), g). The results illustrate that radiance-based light dosimetry is a viable alternative approach to tissue characterization and dosimetry. It is potentially useful for clinical applications because of the limited number of invasive measurements needed and the speed at which the tissue can be characterized.     

Quality assurance in radiotherapy of prostatic cancer

External beam radiotherapy is a widely experimented treatment modality in prostatic cancer. Recently published studies have documented a close dependence of clinical results, in terms of local control and toxicity in particular, on radiation therapy quality. Efforts to improve results of conventional radiotherapy were directed towards the identification of new therapeutic modalities (conformal therapy, fast neutron radiotherapy, neoadjuvant hormonotherapy) as well as towards the optimization of treatment accuracy. In this respect, the following procedures have been particularly effective: 1. the systematic use of CT and retrograde urethrography in PTV definition; 2. immobilization systems which allow a significant reduction in positioning errors; 3. checks before and during treatment by "portal imaging" which allow the identification and correction of a relevant percentage of inaccuracies. The general evolution in treatment planning occurred in recent years has introduced into prostatic cancer radiotherapy new methods and calculation algorithms. While at present the use of new and at the same time complex techniques makes the need for quality assurance of radiation treatments increasingly critical, it is in any case a daily requirement even in most conventional routine treatments.     

Combined use of FLUKA and MCNP-4A for the Monte Carlo simulation of the dosimetry of 10B neutron capture enhancement of fast neutron irradiations

Boron neutron capture enhancement (BNCE) of the fast neutron irradiations use thermal neutrons produced in depth of the tissues to generate neutron capture reactions on 10B within tumor cells. The dose enhancement is correlated to the 10B concentration and to thermal neutron flux measured in the depth of the tissues, and in this paper we demonstrate the feasibility of Monte Carlo simulation to study the dosimetry of BNCE. The charged particle FLUKA code has been used to calculate the primary neutron yield from the beryllium target, while MCNP-4A has been used for the transport of these neutrons in the geometry of the Biomedical Cyclotron of Nice. The fast neutron spectrum and dose deposition, the thermal flux and thermal neutron spectrum in depth of a Plexiglas phantom has been calculated. The thermal neutron flux has been compared with experimental results determined with calibrated thermoluminescent dosimeters (TLD-600 and TLD-700, respectively, doped with 6Li or 7Li). The theoretical results were in good agreement with the experimental results: the thermal neutron flux was calculated at 10.3 X 10(6) n/cm2 s1 and measured at 9.42 X 10(6) n/cm2 s1 at 4 cm depth of the phantom and with a 10 cm X 10 cm irradiation field. For fast neutron dose deposition the calculated and experimental curves have the same slope but different shape: only the experimental curve shows a maximum at 2.27 cm depth corresponding to the build-up. The difference is due to the Monte Carlo simulation which does not follow the secondary particles. Finally, a dose enhancement of, respectively, 4.6% and 10.4% are found for 10 cm X 10 cm or 20 cm X 20 cm fields, provided that 100 micrograms/g of 10B is loaded in the tissues. It is anticipated that this calculation method may be used to improve BNCE of fast neutron irradiations through collimation modifications.     

Monte Carlo dosimetry study of a 6 MV stereotactic radiosurgery unit

Small-field and stereotactic radiosurgery (SRS) dosimetry with radiation detectors, used for clinical practice, have often been questioned due to the lack of lateral electron equilibrium and uncertainty in beam energy. A dosimetry study was performed for a dedicated 6 MV SRS unit, capable of generating circular radiation fields with diameters of 1.25-5 cm at isocentre using the BEAM/EGS4 Monte Carlo code. With this code the accelerator was modelled for radiation fields with a diameter as small as 0.5 cm. The radiation fields and dosimetric characteristics (photon spectra, depth doses, lateral dose profiles and cone factors) in a water phantom were evaluated. The cone factor (St) for a specific cone c at depth d is defined as St(d, c) = D(d, c)/D(d, c(ref)), where c(ref) is the reference cone. To verify the Monte Carlo calculations, measurements were performed with detectors commonly used in SRS such as small-volume ion chambers, a diamond detector, TLDs and films. Results show that beam energies vary with cone diameter. For a 6 MV beam, the mean energies in water at the point of maximum dose for a 0.5 cm cone and a 5 cm cone are 2.05 MeV and 1.65 MeV respectively. The values of St obtained by the simulations are in good agreement with the results of the measurements for most detectors. When the lateral resolution of the detectors is taken into account, the results agree within a few per cent for most fields and detectors. The calculations showed a variation of St with depth in the water. Based on calculated electron spectra in water, the validity of the assumption that measured dose ratios are equal to measured detector readings was verified.     

Quantitative patterns in the clinical manifestations of radiation sickness in large laboratory animals exposed to radiation at superlethal doses. The quantitative patterns in the manifestations of radiation sickness in dogs

Radiation sickness manifestations have been studied in dogs exposed to electrons (electron energy 25 MeV) and gamma-neutron radiation (neutron energies of 0.37 and 1.2 MeV) in a wide dose range. Dose-response relationships have been calculated for mortality and some clinical manifestations of the intestinal and cerebral forms of radiation sickness. With regard to mortality, the highest effect has been observed for gamma-neutron radiation with a neutron energy of 1.2 MeV. For equal physical doses and for those equally effective in relation to mortality, clinical manifestations of damage are more prominent following exposure to electrons.     

Dosimetry of rhenium-186-labeled monoclonal antibodies: methods, prediction from technetium-99m-labeled antibodies and results of phase I trials

Rhenium-186 is a beta-emitting radionuclide that has been studied for applications in radioimmunotherapy. Its 137 keV gamma photon is ideal for imaging the biodistribution of the immunoconjugates and for obtaining gamma camera data for estimation of dosimetry. Methods used for determining radiation absorbed dose are described. We have estimated absorbed dose to normal organs and tumors following administration of two different 186Re-labeled immunoconjugates, intact NR-LU-10 antibody and the F(ab')2 fragment of NR-CO-02. Tumor dose estimates in 46 patients varied over a wide range, 0.4-18.6 rads/mCi, but were similar in both studies. Accuracy of activity estimates in superficial tumors was confirmed by biopsy. Prediction of 186Re dosimetry from a prior 99mTc imaging study using a tracer dose of antibody was attempted in the NR-CO-02 (Fab')2 study. Although 99mTc was an accurate predictor of tumor localization and the mean predicted and observed radiation absorbed doses to normal organs compared favorably, 186Re dosimetry could not be reliably predicted in individual patients. The methods described nevertheless provide adequate estimates of 186Re dosimetry to tumor and normal organs.     

Mathematical description of photobleaching in vivo describing the influence of tissue optics on measured fluorescence signals

The observed decrease in the fluorescence signal during photodynamic therapy (PDT) may contain dosimetric information as this photobleaching provides direct information on the photodynamic processes occurring in the tissue. A correct interpretation of the photobleaching signal, however, is crucial for its use in dosimetry. In this study the influence of scattering and absorption phenomena in tissue on the emitted fluorescence signal are described mathematically. Analytical solutions of the resulting expression show a difference from the single-decaying-exponential function generally used for describing photobleaching signals. The solutions are a function of the fluence rate at the inner side of tissue boundary psi(0*), the photobleaching dose constant beta, the incident irradiation power I0 and time. The accuracy of the results was investigated by comparison of the analytic solutions with numerical calculations using fluence rate profiles and escape functions obtained by Monte Carlo (MC) simulations. Good resemblance is observed when the value for psi(0*) calculated by the MC simulations is used in the analytical solutions. Experimental results in this study indicate the photobleaching dose constant of ALA-induced PpIX to be 33 +/- 3 J cm-2. Determination of beta for different types of photosensitizer and the development of an accurate method to determine psi(0*) can make monitoring of photobleaching during PDT valuable for dosimetry.     

Shielding and radiation safety around a superconducting cyclotron neutron therapy facility

Prior to routine operation of the neutron therapy unit a radiation survey was performed in order to confirm the shielding design and to assure the safety of the personnel involved in the operation of the unit. The shielding requirements were calculated in accordance with NCRP Report No. 51. The contributions of the neutron and gamma dose equivalents have been measured separately outside the treatment room. The exposure outside the shield is negligible. In general, the measured values were lower than those derived from the shielding calculations. The highest total dose equivalents were registered at locations corresponding to the highest calculated values.     

The MIRD perspective 1999. Medical Internal Radiation Dose Committee

The MIRD schema is a general approach for medical internal radiation dosimetry. Although the schema has traditionally been used for organ dosimetry, it is also applicable to dosimetry at the suborgan, voxel, multicellular and cellular levels. The MIRD pamphlets that follow in this issue and in coming issues, as well as the recent monograph on cellular dosimetry, demonstrate the flexibility of this approach. Furthermore, these pamphlets provide new tools for radionuclide dosimetry applications, including the dynamic bladder model, S values for small structures within the brain (i.e., suborgan dosimetry), voxel S values for constructing three-dimensional dose distributions and dose-volume histograms and techniques for acquiring quantitative distribution and pharmacokinetic data.     

Design and dosimetric characteristics of a high dose rate remotely afterloaded endocavitary applicator system

PURPOSE: An applicator is described for endocavitary treatment of rectal cancers using a high dose rate (HDR) remote afterloading system with a single high-intensity 192Ir source as an alternative to the 50 kVp x-ray therapy contact unit most frequently used in this application. METHODS AND MATERIALS: The applicator consists of a tungsten-alloy collimator with a 45 degree beveled end, placed in a protoscope with an elliptical cross-section. The resultant 3 cm diameter circular treatment aperture, located in the beveled face of the proctoscope, is irradiated by circular array of dwell positions located about 6.5 mm from the applicator surface. This beveled end allows patients with posterior wall tumors to be treated in the dorsal lithotomy position. The dose-rate distributions about the applicator were determined using a combination of thermoluminescent dosimetry (TLD-100 detectors) and radiochromic film dose measurement techniques along with Monte Carlo dosimetry calculations. TLD-100 (3 x 3 x 0.9 mm3 chips) measurements were used to measure the distribution of dose over the proctoscope surface as well as the central axis dose-rate distribution. Relative radiochromic film measurements were used to measure off-axis ratios (flatness and penumbra width) within the treatment aperture. These data were combined with Monte Carlo simulation results to obtain the final dose distribution. RESULTS: The tungsten collimator successfully limits the dose to the tissue in contact with the proctoscope walls to less than 12% of the prescribed dose. These results indicate that the HDR applicator system has slightly more penetrating depth-dose characteristics than the most widely used contact therapy x-ray machine. Flatness characteristics of the two treatment delivery systems are comparable, although the HDR endocavitary applicator has a significantly wider penumbra. Finally, the HDR applicator has a lower surface dose rate (1.5-4 Gy/min of dwell time) compared to 9-10 Gy/min for the x-ray unit. CONCLUSIONS: An applicator system has been developed for endocavitary treatment of early stage rectal carcinoma that uses a single-stepping source HDR remote afterloading system as a radiation source. The advantages of the HDR-based system over x-ray therapy contact units currently used in this clinical application are (a) enhanced flexibility in applicator design and (b) widespread availability of single-stepping source HDR remote afterloading systems.     

Prostaglandins attenuate cardiac contractile dysfunction produced by free radical generation but not by hydrogen peroxide

Both fast neutron radiotherapy and boron neutron capture therapy have been investigated as new radiation treatment techniques for patients with malignant gliomas. While each of these techniques individually has shown the potential for pathological eradication of malignant glioma, to date neither has evolved into an accepted, improved method of treatment. We have recently begun a research program investigating the feasibility of combining the benefits of both types of therapy. As a fast neutron beam penetrates tissue some of the particles are degraded to thermal energies. These can be captured by 10B or other suitable isotopes resulting in a highly-localized release of additional energy during a course of fast neutron radiotherapy. In this article we will review the rationale for such an approach, and review the underlying physics as well as in vitro, in vivo, and early human studies testing its feasibility. If appropriate carrier agents can be found that preferentially-localize in tumor cells, this approach ena be applied to many different tumor systems.     

Application of fission track detectors to californium-252 neutron dosimetry in tissue near the radiation source

Fission track detectors were applied to a unique problem in neutron dosimetry. Measurements of neutron doses were required at locations within a tumor of 1 cm diameter implanted on the back of a mouse and surrounded by a square array of four 252Cf medical sources. Measurements made in a tissue-equivalent mouse phantom showed that the neutron dose rate to the center of the tumor was 2.18 rads micrograms-1 h-1 +/- 8.4%. The spatial variation of neutron dose to the tumor ranged from 1.88 to 2.55 rads micrograms-1 h-1. These measurements agree with calculated values of neutron dose to those locations in the phantom. Fission track detectors have been found to be a reliable tool for neutron dosimetry for geometries in which one wishes to know neutron dose values which may vary considerably over distances of 1 cm or less.     

Fourier transform Raman spectroscopy of polyacrylamide gels (PAGs) for radiation dosimetry

Polyacrylamide gels (PAGs) are used for magnetic resonance imaging radiation dosimetry. Fourier transform (FT) Raman spectroscopy studies were undertaken to investigate cross-linking changes during the copolymerization of polyacrylamide gels in the spectral range of 200-3500 cm(-1). Vibrational bands of 1285 cm(-1) and 1256 cm(-1) were assigned to acrylamide and bis-acrylamide single CH2 deltaCH2 binding modes. Bands were found to decrease in amplitude with increasing absorbed radiation dose as a result of copolymerization. Principal component regression was performed on FT-Raman spectra of PAG samples irradiated to 50 Gy. Two components were found to be sufficient to account for 98.7% of the variance in the data. Cross validation was used to establish the absorbed radiation dose of an unknown PAG sample from the FT-Raman spectra. The calculated correlation coefficient between measured and predictive samples was 0.997 with a standard error of estimate of 0.976 and a standard error of prediction of 1.140. Results demonstrate the potential of FT-Raman spectroscopy for ionizing radiation dosimetry using polyacrylamide gels.