Gamma Putty dosimetric studies in electron beam.

Traditionally, lead has been used for field shaping in megavoltage electron beams in radiation therapy. In this study, we analyze the dosimetric parameters of a nontoxic, high atomic number (Z = 83), bismuth-loaded material called Gamma Putty that is malleable and can be easily molded to any desired shape. First, we placed an ionization chamber at different depths in a solid water phantom under a Gamma Putty shield of thickness (t = 0, 3, 5, 10, 15, 20, and 25 mm, respectively) and measured the ionizing radiation on the central axis (CAX) for electron beam ranging in energies from 6 to 20 MeV. Next, we investigated the relationship between the relative ionization (RI) measured at a fixed depth for several Gamma Putty shield at different cutout diameters ranging from 2 to 5 cm for various beam energies and derived an exponential fitting equation for clinical purposes. The dose profiles along the CAX show that bremsstrahlung dominates for Gamma Putty thickness >15 mm. For high-energy beams (12-20 MeV) and all Gamma Putty thicknesses up to 25 mm, RI below 5% could not be achieved due to the strong bremsstrahlung component. However, Gamma Putty is a very suitable material for reducing the transmission factor below 5% and protecting underlying normal tissues for low-energy electron beams (6-9 MeV).

First clinical implementation of the Capri applicator.

This study was to assess the Capri applicator for patients with endometrial cancer undergoing high-radiation dose treatments following external-beam radiation therapy. The Capri applicator is an inflatable vaginal cylinder with multiple channels. It is used to tailor the dose distribution to an asymmetric vaginal disease, and better spare organs at risk. Five patients with high-risk endometrial cancer were selected for this study. The patients were treated with a high dose of radiation using the Capri applicator: daily fraction of 7 Gy was prescribed for a total dose of 21Gy. The treatment plans included radiobiological parameters such as equivalent uniform dose (EUD), normal tissue complication probability (NTCP), and tumor control probability (TCP). Based on the dose-volume histograms (DVH), we also calculated four quality factors: conformity index (CI), dose homogeneity index (DHI), dose nonuniformity index (DNR), and overdose index (OI). The TCP values range from 82.26% to 95.92%. Very low values of NTCP were observed for the bladder and rectum. The EUDs to organs at risk ranged from 4.65 Gy to 18.22 Gy for the bladder, and from 3.41 Gy from to 6.56 Gy for the rectum. The mean CI was 1.05 (SD = 0.0008). The mean DNR was 0.10 (range 0.0-0.295, SD= 0.100). The mean OI was 0.019 (SD = 0.028). The DHIs were in the range of 1.0-0.754 (mean 0.886, SD = 0.116). The use of a multichannel vaginal cylinder may not only help cover extensive vaginal disease, but also reduce the dose to the rectum. This dosimetric analysis shows that rectal doses could be reduced using a multichannel cylinder. However, the dose delivered to the bladder based on EUD calculation may be higher than that obtained with other methods. Each patient must be evaluated independently to determine if a multichannel treatment is appropriate. Clinical followup will show whether this rectal dose sparing translates into a real toxicity improvement.

Dosimetric assessment of prostate cancer patients through principal component analysis (PCA).

The aims of this study were twofold: first, to determine the impact of variance in dose-volume histograms (DVH) on patient-specific toxicity after 2 high-dose fractions in a sample of 22 men with prostate cancer; and second, to compare the effectiveness of traditional DVH analysis and principal component analysis (PCA) in predicting rectum and urethra toxicity. A series of 22 patients diagnosed with prostate adenocarcinoma was treated with 45 Gy external beam and 20 Gy dose rate brachytherapy. Principal component analysis was applied to model the shapes of the rectum and urethra dose-volume histograms. We used logistic regression to measure the correlations between the principal components and the incidence of rectal bleeding and urethra stricture. We also calculated the equivalent uniform dose (EUD) and normal tissue complication probability (NTCP) for the urethra and rectum, and tumor control probability (TCP) for the prostate using BioSuite software. We evaluated their correlations with rectal and urethra toxicity. The rectum DVHs are well described by one principal component (PC1), which accounts for 93.5% of the variance in their shapes. The urethra DVHs are described by two principal components, PC1 and PC2, which account for 94.98% and 3.15% of the variance, respectively. Multivariate exact logistic regression suggests that urethra PC2 is a good predictor of stricture, with Nagelkerke's R2 estimated at 0.798 and a Wald criterion of 5.421 (p < 0.021). The average NTCPs were 0.06% ± 0.04% and 1.25% ± 0.22% for the rectum and urethra, respectively. The average TCP was 85.29% ± 2.28%. This study suggests that principal component analysis can be used to identify the shape variation in dose-volume histograms, and that the principal components can be correlated with the toxicity of a treatment plan based on multivariate analysis. The principal components are also correlated with traditional dosimetric parameters.

Discrepancies in determining electron energy for lumpectomy boost treatment.

The aim of this study was to compare lumpectomy cavity depth measurements obtained through ultrasound (U/S) and retrospective computed tomography (CT). Twenty-five patients with stage T1-2 invasive breast cancer formed the cohort of this study. Their U/S and CT measurements were converted into electron energy and compared. The mean U/S depth was 3.6 ± 1.3 cm, while the mean CT depth was 4.9 ± 1.9 cm; the listed error ranges are one standard deviation. Electron energies for treatment ranged from 6 MeV to 12 MeV based on the U/S determination. There was no significant correlation between cavity depths measured by U/S and CT (R(2)= 0.459, P < 0.002). Furthermore, only 20% of CT-based electron energy determinations matched the corresponding U/S determinations. This ratio increased to 40% when taking into account an upper limit based on the depth of organs at risk below the cavity. The study shows that there is a significant discrepancy between cavity depths determined by U/S and CT. It also supports the concept that post-lumpectomy radiotherapy boosts should be tailored according to the needs and comfort of individual practices and institutions.

A case report on bilateral partial breast irradiation using SAVI.

To assess dosimetric parameters in a case study where bilateral accelerated partial breast irradiation (APBI) is delivered using a strut-adjusted volume implant (SAVI) device. A 59-year-old female received APBI in both breasts over 5 days, with fractions of 3.4 Gy twice daily. A Vac-lok system was used for immobilization, and a C-arm was used for daily imaging. We generated dose-volume histograms (DVHs) for the brachytherapy plans to derive several important biologic factors. We calculated the normal tissue complication probability (NTCP), equivalent uniform dose (EUD), and tumor control probability (TCP) using the Lyman-Kutcher-Burman model parameters α = 0.3 Gy(-1), α/ß = 4 Gy, n = 0.1, and m = 0.3. In addition, we assessed the dose homogeneity index (DHI), overdose index, and dose nonuniformity ratio. D95 was >95% and V150 was <50 mL for both breasts. The DHIs were 0.469 and 0.512 for the left and right breasts, respectively. The EUDs (normalized to 3.4 Gy b.i.d.) were 33.53 and 29.10 Gy. The TCPs were estimated at 99.2% and 99.9%, whereas the NTCP values were 4.2% and 2.57%. In this clinical case, we were able to quantify the dosimetric parameters of an APBI treatment performed with a SAVI device.

RapidArc quality assurance through MapCHECK.

The purpose is to devise a patient-specific quality assurance procedure for RapidArc radiotherapy using the MapCHECK detector array. We use our existing MapCHECK system and a Solid Water phantom with an embedded ion chamber to develop a quality assurance procedure for RapidArc treatment after commissioning. The ion chamber used to measure the absolute dose is surrounded by 6 cm layers of solid water on the anterior and posterior sides. Partial arcs derived from the treatment planning system were used with MapCHECK to determine the actual shape of the dose and correct for the angular dependence. The ion chamber measurements were within 1% of the absolute doses predicted by the Eclipse treatment system. When using a partial arc from 60° to 300° on the MapCHECK array (gamma index <1: 3%, 3 mm, 10% threshold), we obtain a 97.52% average passing rate. A combination of ion chamber phantoms, partial arcs and the MapCHECK system can be used for quality assurance of RapidArc therapies.

Dosimetric parameters in partial breast irradiation through brachytherapy.

The objective of this work is to evaluate biological models and dose homogeneity in a new partial breast irradiation method, the MammoSite RTS. The study is based on 11 patients who received the therapy. For each patient, we determined the dose volume distribution delivered to the breast. Based on these data, we estimate some important biological parameters. Eleven patients with early-stage, invasive, ductal breast cancer were treated using MammoSite RTS brachytherapy, which delivers radiation through a balloon placed in the lumpectomy bed. The radiation was provided by an Iridium-192 source, and 340 cGy were delivered per fraction twice daily. We calculated some commonly used dosimetric parameters, and evaluated the biological parameters tumor control probability (TCP) and normal tissue complication probability (NTCP). We also looked for correlations among these parameters. The average equivalent uniform dose (EUD), NTCP, and TCP were 43.66 Gy, 47.95%, and 91.78%, respectively. The coefficient of variation (CV) among the patients was very low for all 3 parameters. Two dose homogeneity indices (DHI and the S-index) are strongly correlated (r = -0.815). The area under the dose-volume histogram (DVH) and the treatment volume (TXV) also showed a strong correlation (r = 0.995, p < 0.0001). A simplified logit Poisson-EUD model is suitable for determining NTCP and TCP. Other factors such as the area under the DVH and dose homogeneity indices are also useful in planning radiotherapy treatments for early breast cancer.

A Bland-Altman analysis of the bias between computed tomography and ultrasound prostate volume measurements.

This study assesses the agreement between computed tomography (CT) measurements of prostate volume and those obtained by ultrasound (US), a well-established non-invasive technique. Twenty-six patients aged between 58 and 74 years were evaluated for prostate seed implant therapy using both CT and US measurements. The level of agreement between these 2 methods, which were strongly correlated (R2 = 0.828; p < 0.0001), was determined through Bland-Altman analysis. The mean prostate volume (+/- one standard deviation) of the sample was 31.8 +/- 10.5 cc for the CT method and 27.0 +/- 8.2 cc for the US method. The prostate volumes obtained by CT were, on average, 17% larger than the corresponding volumes determined by US. The average bias between the 2 imaging methods is 4.80 cc or 15%, which is significantly larger than the clinically acceptable margin of 10%.

Whole-body lifetime occupational lead exposure and risk of Parkinson's disease.

BACKGROUND: Several epidemiologic studies have suggested an association between Parkinson's disease (PD) and exposure to heavy metals using subjective exposure measurements. OBJECTIVES: We investigated the association between objective chronic occupational lead exposure and the risk of PD. METHODS: We enrolled 121 PD patients and 414 age, sex, and race, frequency-matched controls in a case-control study. As an indicator of chronic Pb exposure, we measured concentrations of tibial and calcaneal bone Pb stores using 109Cadmium excited K-series X-ray fluorescence. As an indicator of recent exposure, we measured blood Pb concentration. We collected occupational data on participants from 18 years of age until the age at enrollment, and an industrial hygienist determined the duration and intensity of environmental Pb exposure. We employed physiologically based pharmacokinetic modeling to combine these data, and we estimated wholebody lifetime Pb exposures for each individual. Logistic regression analysis produced estimates of PD risk by quartile of lifetime Pb exposure. RESULTS: Risk of PD was elevated by > 2-fold [odds ratio = 2.27 (95% confidence interval, 1.13-4.55); p = 0.021] for individuals in the highest quartile for lifetime lead exposure relative to the lowest quartile, adjusting for age, sex, race, smoking history, and coffee and alcohol consumption. The associated risk of PD for the second and third quartiles were elevated but not statistically significant at the alpha = 0.05 level. CONCLUSIONS: These results provide an objective measure of chronic Pb exposure and confirm our earlier findings that occupational exposure to Pb is a risk factor for PD.

Evaluation of porfimer sodium in dogs and cats with spontaneous tumors.

The effect of photodynamic therapy is a function of several variables, including selective retention of the drug in tumor tissue with reduced drug concentration in surrounding normal tissue. A study was designed to determine the pharmacokinetic profile and variability of porfimer sodium in dogs and cats with spontaneous tumors and to thereby determine the optimal timing of its photoactivation in these species. The results of this study indicate that there is marked variability among species in the distribution of porfimer sodium between highly proliferating tissues, which requires careful attention in the design of human and veterinary application of photodynamic therapy with porfimer sodium, as determined in rodent models.

Biodistribution of three photosensitizers in dogs with spontaneous tumors.

Photodynamic therapy (PDT) has been considered a potential method for tumor eradication. The present study was designed to assess the efficacy of PDT as an alternative treatment approach. Photosensitizers, such as porfimer sodium, tin ethyl etiopurpurin, and aluminum chlorophthalocyanine, were administered i.v. to dogs, and tissue samples were harvested 24 to 300 hours later. The uptake of the photosensitizers in tumor (fibrosarcoma) and adjacent normal tissue biopsies was quantified by tissue solubilization technique and fluorimetry. In addition, the pharmacokinetics and selectivity of the photosensitizers were addressed by two-phase exponential function and specific uptake ratio, respectively. Porfimer sodium exhibited a longer elimination half-life (175.3 hr), slower clearance (0.0028 L/kg/hr), and a larger area under the curve (1075 microg/g/hr) in tumors than did tin ethyl etiopurpurin or aluminum chlorophthalocyanine. As a result, porfimer sodium showed a good selectivity in tumors located in muscle and skin. The study provided clinical information for determination of the efficacy of different PDT alternatives.

Threshold dose of three photosensitizers in dogs with spontaneous tumors.

Photodynamic threshold doses in dogs with spontaneous tumors can be achieved through a mathematical model. For this to be clinically relevant, it is important to know the treatment parameters for tissue necrosis. The threshold dose for three photosensitizers (porfimer sodium, aluminum cholorophthalocyanine [AlClPc], and tin ethyl etiopurpurin [SnET2]) commonly used in veterinary chemotherapy protocols was evaluated in 12 dogs with spontaneous tumors. To derive the photodynamic threshold dose, the tissue optical properties of each compound were determined by diffuse reflectance and thus the light fluence rate. Uptake was measured by fluorimetry using tissue solubilization techniques. The threshold values calculated were highest for AlClPc (irradiated 48 hours after administration). The radius of necrosis (4.00 to 5.48 mm) and photosensitizer uptake (3.4 to 6.91 microg/g) were elevated after injection of porfimer sodium. The threshold dose model described here is photosensitizer dependent but independent of photosensitizer uptake and light dose. This study indicates that more photon absorption is needed for tumor necrosis with AlClPc than for either SnET2 or porfimer sodium.