The association of intraprostatic calcifications and dosimetry parameters with biochemical control after permanent prostate implant.

PURPOSE: The objective of this study was to evaluate the impact of intraprostatic calcifications (IC) on long-term tumor control in patients treated with permanent implant prostate brachytherapy (PIPB). MATERIALS AND METHODS: Data from 609 I-125 patients treated with PIPB were retrospectively reviewed. The presence of IC was determined by reviewing postimplant CT images. Doses delivered were determined using the Monte Carlo (model-based) calculations and the TG43 approach. Biochemical relapses at 7 and 10 years were determined according to Phoenix definition. Long-term biochemical relapse-free survival (bRFS) was determined using Kaplan-Meier estimates with log rank test. Cox proportional hazard models were used for analysis of predictor factors of biochemical recurrence. RESULTS: IC were observed for 11.1% of patients. Clinical stage, PSA, Gleason score, D'Amico risk group, and ADT use were comparable between IC and no IC groups. The 7- and 10-year bRFS for the entire cohort were 94.1% and 90.6%, respectively. The bRFS at 7 years was 90.5% (with IC) vs. 94.5% (without IC) (p = 0.198); the corresponding values at 10 years were 78.8% vs. 91.8% (p = 0.046). On Cox model, only prostatic calcifications were a significant risk factor for biochemical relapse (HR: 2.30, IC 95%: 1.05-5.00, p = 0.037; and HR: 3.94; IC 95%: 1.00-15.38; p = 0.049 for univariate and multivariate analysis, respectively). CONCLUSION: The presence of IC in patients treated with PIPB decreases V100 and D90 for postimplant Monte Carlo dosimetry (compared with TG43); correspondingly, IC are associated with a lower 10-y bRFS. Model-based dose calculations are critical to evaluate potential cold spots due to calcifications.

Dosimetric and radiobiological investigation of permanent implant prostate brachytherapy based on Monte Carlo calculations.

PURPOSE: Permanent implant prostate brachytherapy plays an important role in prostate cancer treatment, but dose evaluations typically follow the water-based TG-43 formalism, ignoring patient anatomy and interseed attenuation. The purpose of this study is to investigate advanced TG-186 model-based dose calculations via retrospective dosimetric and radiobiological analysis for a new patient cohort. METHODS AND MATERIALS: A cohort of 155 patients treated with permanent implant prostate brachytherapy from The Ottawa Hospital Cancer Centre is considered. Monte Carlo (MC) dose calculations are performed using tissue-based virtual patient models. Dose-volume histogram (DVH) metrics (target, organs at risk) are extracted from 3D dose distributions and compared with those from calculations under TG-43 assumptions (TG43). Equivalent uniform biologically effective dose and tumor control probability are calculated. RESULTS: For the target, D90 (V100) is 136.7 ± 20.6 Gy (85.8% ± 7.8%) for TG43 and 132.8 ± 20.1 Gy (84.1% ± 8.2%) for MC; D90 is 3.0% ± 1.1% lower for MC than TG43. For organs at risk, MC D1cc = 104.4 ± 27.4 Gy (TG43: 106.3 ± 28.3 Gy) for rectum and 80.8 ± 29.7 Gy (TG43: 78.4 ± 28.4 Gy) for bladder; D1cc = 185.9 ± 30.2 Gy (TG43: 191.1 ± 32.0 Gy) for urethra. Equivalent uniform biologically effective dose and tumor control probability are generally lower when evaluated using MC doses. The largest dosimetric and radiobiological discrepancies between TG43 and MC are for patients with intraprostatic calcifications, for whom there are low doses (cold spots) in the vicinity of calcifications within the target, identified with MC but not TG43. CONCLUSIONS: DVH metrics and radiobiological indices evaluated with TG43 are systematically inaccurate by upward of several percent compared with MC patient-specific models. Mean cohort DVH metrics and their MC:TG43 variances are sensitive to patient cohort and clinical practice, underlining the importance of further retrospective MC studies toward widespread clinical adoption of advanced model-based dose calculations.

Coupling I-125 permanent implant prostate brachytherapy Monte Carlo dose calculations with radiobiological models.

PURPOSE: To investigate the coupling of radiobiological models with patient-specific Monte Carlo (MC) dose calculations for permanent implant prostate brachytherapy (PIPB). To compare radiobiological indices evaluated with different radiobiological models using MC and simulated AAPM TG-43 dose calculations. METHODS: Three-dimensional dose distributions previously computed using MC techniques with two types of patient models, TG43sim (AAPM TG-43 water-based conditions) and MCDmm (realistic tissues and interseed effects), for 613 PIPB patients are coupled with biological dose and tumour control probability (TCP) models. Two approaches and their extensions are considered to evaluate biological doses, biologically effective dose (BED) and isoeffective dose (IED), as well as two methods to evaluate TCP. Three novel extensions of equivalent uniform biologically effective dose (EUBED) are suggested which consider the spatial distribution of doses within the target volume. Adopted radiobiological model parameter values (α, ß, etc) are those suggested by AAPM TG-137, and sensitivity to parameter choice is discussed. RESULTS: MCDmm dose calculations can reveal low doses in the prostate target volume, due to tissue heterogeneities or inter-seed effects; considering these low doses in EUBED calculations can lower TCP estimates by up to 70%, with largest differences in patients with calcifications. There are large variations in biological doses and TCPs evaluated over the 613 patient cohort for each radiobiological model considered, reflecting the spectrum of physical doses calculated for these patients with either MCDmm or TG43sim. Depending on the model details, BED, IED and EUBED are, on average, 6.0-9.8%, 7.4-9.2% and 1.8-15% higher, respectively, with TG43sim than MCDmm. TCP estimates computed using MCDmm dose distributions are much lower than expected based on past treatment outcome studies, suggesting a need to re-assess model parameters when evaluating radiobiological indices coupled with heterogeneous tissue model-based dose calculations. CONCLUSIONS: Cohort average differences in biological dose and TCP estimates between radiobiological models are generally larger than differences for any one radiobiological model evaluated with TG43sim or MCDmm dose calculations. However, heterogeneous tissue dose calculations, like MCDmm, can identify clinically-relevant low dose volumes, e.g., in patients with calcifications, which would otherwise be missed with TG-43. In addition to affecting physical dose distributions, these low dose volumes can largely impact radiobiological dose and TCP estimates, which further motivates the clinical implementation of model-based dose calculations for PIPB.

Large-scale Retrospective Monte Carlo Dosimetric Study for Permanent Implant Prostate Brachytherapy.

PURPOSE: To retrospectively compare water-based and full tissue model Monte Carlo dose calculations in a large cohort of patients undergoing 125I permanent implant prostate brachytherapy. METHODS AND MATERIALS: For 613 patients, EGSnrc BrachyDose dose calculations were performed in 2 virtual patient models: TG43sim (simulated American Association of Physicists in Medicine Task Group Report 43 conditions) and MCref (computed tomography-derived heterogeneous tissue model with interseed effects). A sensitivity analysis was performed in a patient subset (25 with and 25 without prostatic calcifications) to explore dose calculation dependence on organ-at-risk (OAR) and calcification tissue elemental compositions and modelling approach. RESULTS: In the target volume, the minimum radiation dose delivered to 90% of prostate (D90) (volume of prostate receiving at least 100% of prescription dose [V100]) was lower with MCref than with TG43sim by 5.9% ± 1.6% (2.6% ± 1.7%), on average. Patients with prostatic calcifications can have substantial underdosed volumes due to calcification shielding, lowering the D90 by ≤25%. In the urethra, the average D5 (D30) was lower with MCref than with TG43sim by 4.4% ± 1.8% (4.7% ± 1.9%). In the rectum (bladder), the minimum dose to the hottest 0.1 cm3 (D_0.1cm3) of the contoured organ was lower (higher) with MCref than with TG43sim by 5.2% ± 1.8% (1.3% ± 1.8%). Doses to the target and OARs can increase or decrease by several percentages, depending on the assumed tissue elemental composition. In patients with calcifications, differences between approaches to model calcifications can change the target and OAR dose metrics by upward of 10%. CONCLUSIONS: TG43sim typically overestimates the target and OAR doses by several percentages, on average, compared with MCref. The considerable variation in the relative TG43sim and MCref doses between patients, and the larger dose differences for patients with calcification, suggests that clinical adoption of Monte Carlo dose calculations for permanent implant prostate brachytherapy should be pursued. The substantial sensitivity of the Monte Carlo dose calculations to the patient modelling approach supports the adoption of a consensus modelling scheme, such as MCref described in the present study, to ensure consistency of practice.

Altered transition metal homeostasis in mice following manganese injections for manganese-enhanced magnetic resonance imaging.

In manganese-enhanced magnetic resonance imaging (MEMRI), the paramagnetic divalent ion of manganese (Mn(2+)) is injected into animals to generate tissue contrast, typically at much higher exposures than have been previously used in studies of Mn toxicity. Here we investigate the effect of these injections on the homeostasis of the transition metals iron and copper in mice to see if there are disruptions which should be considered in MEMRI studies. Manganese shares transport proteins with other transition metals including iron and copper, so it is possible that changes in manganese levels in tissue following injections of the metal may affect other metal levels too. This in turn may affect MRI contrast or the investigation of disease processes in the animal models being imaged. In this study, we measured manganese, iron, and copper concentrations in the blood, kidney, liver and in brain regions in mice treated with four injections of 30 mg/kg MnCl(2) 4H(2)O (dry chemical weight/body weight)-a common dose used in MEMRI. In addition to the expected increases in manganese in tissues, we noted a statistically significant reduction in copper in the kidney and liver. Also, we noted a statistically significant decrease in concentration of iron in the thalamus of the brain. These findings suggest that the high doses of manganese injected in MEMRI studies can disrupt the homeostasis of other transition metals in mice.

Estimating effective dose to pediatric patients undergoing interventional radiology procedures using anthropomorphic phantoms and MOSFET dosimeters.

OBJECTIVE: The purpose of this study was to estimate the effective doses received by pediatric patients during interventional radiology procedures and to present those doses in "look-up tables" standardized according to minute of fluoroscopy and frame of digital subtraction angiography (DSA). MATERIALS AND METHODS: Organ doses were measured with metal oxide semiconductor field effect transistor (MOSFET) dosimeters inserted within three anthropomorphic phantoms, representing children at ages 1, 5, and 10 years, at locations corresponding to radiosensitive organs. The phantoms were exposed to mock interventional radiology procedures of the head, chest, and abdomen using posteroanterior and lateral geometries, varying magnification, and fluoroscopy or DSA exposures. Effective doses were calculated from organ doses recorded by the MOSFET dosimeters and are presented in look-up tables according to the different age groups. RESULTS: The largest effective dose burden for fluoroscopy was recorded for posteroanterior and lateral abdominal procedures (0.2-1.1 mSv/min of fluoroscopy), whereas procedures of the head resulted in the lowest effective doses (0.02-0.08 mSv/min of fluoroscopy). DSA exposures of the abdomen imparted higher doses (0.02-0.07 mSv/DSA frame) than did those involving the head and chest. CONCLUSION: Patient doses during interventional procedures vary significantly depending on the type of procedure. User-friendly look-up tables may provide a helpful tool for health care providers in estimating effective doses for an individual procedure.