A Monte Carlo study of I-125 prostate brachytherapy with gold nanoparticles: dose enhancement with simultaneous rectal dose sparing via radiation shielding.

We investigate via Monte Carlo simulations a new 125I brachytherapy treatment technique for high-risk prostate cancer patients via injection of Au nanoparticle (AuNP) directly into the prostate. The purpose of using the nanoparticles is to increase the therapeutic index via two synergistic effects: enhanced energy deposition within the prostate and simultaneous shielding of organs at risk from radiation escaping from the prostate. Both uniform and non-uniform concentrations of AuNP are studied. The latter are modeled considering the possibility of AuNP diffusion after the injection using brachy needles. We study two extreme cases of coaxial AuNP concentrations: centered on brachy needles and centered half-way between them. Assuming uniform distribution of 30 mg g-1 of AuNP within the prostate, we obtain a dose enhancement larger than a factor of 2 to the prostate. Non-uniform concentration of AuNP ranging from 10 mg g-1 and 66 mg g-1 were studied. The higher the concentration in a given region of the prostate the greater is the enhancement therein. We obtain the highest dose enhancement when the brachytherapy needles are coincident with AuNP injection needles but, at the same time, the regions in the tail are colder (average dose ratio of 0.7). The best enhancement uniformity is obtained with the seeds in the tail of the AuNP distribution. In both uniform and non-uniform cases the urethra and rectum receive less than 1/3 dose compared to an analog treatment without AuNP. Remarkably, employing AuNP not only significantly increases dose to the target but also decreases dose to the neighboring rectum and even urethra, which is embedded within the prostate. These are mutually interdependent effects as more enhancement leads to more shielding and vice-versa. Caution must be paid since cold spot or hot spots may be created if the AuNP concentration versus seed position is not properly distributed respect to the seed locations.

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.

Computer simulations of thermal tissue remodeling during transvaginal and transurethral laser treatment of female stress urinary incontinence.

BACKGROUND AND OBJECTIVES: A non-surgical method is being developed for treating female stress urinary incontinence by laser thermal remodeling of subsurface tissues with applied surface tissue cooling. Computer simulations of light transport, heat transfer, and thermal damage in tissue were performed, comparing transvaginal and transurethral approaches. STUDY DESIGN/MATERIALS AND METHODS: Monte Carlo (MC) simulations provided spatial distributions of absorbed photons in the tissue layers (vaginal wall, endopelvic fascia, and urethral wall). Optical properties (n,µa ,µs ,g) were assigned to each tissue at λ = 1064 nm. A 5-mm-diameter laser beam and incident power of 5 W for 15 seconds was used, based on previous experiments. MC output was converted into absorbed energy, serving as input for finite element heat transfer simulations of tissue temperatures over time. Convective heat transfer was simulated with contact probe cooling temperature set at 0°C. Variables used for thermal simulations (κ,c,ρ) were assigned to each tissue layer. MATLAB code was used for Arrhenius integral thermal damage calculations. A temperature matrix was constructed from ANSYS output, and finite sum was incorporated to approximate Arrhenius integral calculations. Tissue damage properties (Ea ,A) were used to compute Arrhenius sums. RESULTS: For the transvaginal approach, 37% of energy was absorbed in the endopelvic fascia target layer with 0.8% deposited beyond it. Peak temperature was 71°C, the treatment zone was 0.8-mm-diameter, and 2.4 mm of the 2.7-mm-thick vaginal wall was preserved. For transurethral approach, 18% energy was absorbed in endopelvic fascia with 0.3% deposited beyond the layer. Peak temperature was 80°C, treatment zone was 2.0-mm-diameter, and 0.6 mm of 2.4-mm-thick urethral wall was preserved. CONCLUSIONS: Computer simulations suggest that transvaginal approach is more feasible than transurethral approach. Lasers Surg. Med. 49:198-205, 2017. © 2016 Wiley Periodicals, Inc.

Assessment of the feasibility of using transrectal ultrasound for postimplant dosimetry in low-dose-rate prostate brachytherapy.

A study was performed to establish whether transrectal ultrasound (TRUS)-based postimplant dosimetry (PID) is both practically feasible and comparable to computed tomography (CT)-based PID, recommended in current published guidelines. In total, 22 patients treated consecutively at a single cancer center with low-dose-rate (LDR) brachytherapy for early-stage prostate cancer had a transrectal ultrasound performed immediately after implant (d0-TRUS) and computed tomography scan 30 days after implant (d30-CT). Postimplant dosimetry planning was performed on both image sets and the results were compared. The interobserver reproducibility of the transrectal ultrasound postimplant dosimetry planning technique was also assessed. It was noticed that there was no significant difference in mean prostate D90 (136.5Gy and 144.4Gy, p = 0.2197), V100 (86.4% and 89.1%, p = 0.1480) and V150 (52.0% and 47.8%, p = 0.1657) for d30-CT and d0-TRUS, respectively. Rectal doses were significantly higher for d0-TRUS than d30-CT. Urethral doses were available with d0-TRUS only. We have shown that d0-TRUS PID is a useful tool for assessing the quality of an implant after low-dose-rate prostate brachytherapy and is comparable to d30-CT PID. There are clear advantages to its use in terms of resource and time efficiency both for the clinical team and the patient.

Transcorporal artificial urinary sphincter in radiated and non - radiated compromised urethra. Assessment with a minimum 2 year follow-up.

PURPOSE: to assess the efficacy of transcorporal artificial urinary sphincter (AUS) implantation on continence for male stress urinary incontinence in cases of prior surgical treatment or/and radiation failure, and as a first option in radiation patients. MATERIALS AND METHODS: From March 2007 to August 2012, 37 male patients were treated with transcorporal AUS AMS™ 800. Twelve patients had primary placement of transcorporal cuff, a surgical option due to a previous history of radiation and 25 patients had secondary procedure after failure of AUS or urinary incontinence surgery. Functional urinary outcomes were assessed by daily pad use, 24-hour Pad-test and ICIQ-SF questionnaire. Quality of life and satisfaction were assessed based on I-QoL and PGI-I questionnaires. RESULTS: After a median of 32 months, the continence rate (0 to 1 pad) was 69.7%. Median pad test was 17.5g (0-159), mean ICIQ-SF score was 7.3/21 (±5.4) and mean I-QoL score was 93.9/110. A total of 88% of the patients reported satisfaction with the AUS. The 5-year actuarial revision-free for AUS total device was 51%. Patients for primary implant for radiation were not more likely to experience revision than non-radiation patients. Preservation of erections was reported in half of the potent patients. CONCLUSIONS: Transcorporal AUS cuff placement is a useful alternative procedure option for severe male UI treatment, especially in patients with a compromised urethra after prior surgery or radiation. A high continence rate was reported and implantation as first option in radiation patients should be considered.

Transcorporal artificial urinary sphincter in radiated and non - radiated compromised urethra. Assessment with a minimum 2 year follow-up

ABSTRACT Purpose to assess the efficacy of transcorporal artificial urinary sphincter (AUS) implantation on continence for male stress urinary incontinence in cases of prior surgical treatment or/and radiation failure, and as a first option in radiation patients. Materials and Methods From March 2007 to August 2012, 37 male patients were treated with transcorporal AUS AMS™ 800. Twelve patients had primary placement of transcorporal cuff, a surgical option due to a previous history of radiation and 25 patients had secondary procedure after failure of AUS or urinary incontinence surgery. Functional urinary outcomes were assessed by daily pad use, 24-hour Pad-test and ICIQ-SF questionnaire. Quality of life and satisfaction were assessed based on I-QoL and PGI-I questionnaires. Results After a median of 32 months, the continence rate (0 to 1 pad) was 69.7%. Median pad test was 17.5g (0-159), mean ICIQ-SF score was 7.3/21 (±5.4) and mean I-QoL score was 93.9/110. A total of 88% of the patients reported satisfaction with the AUS. The 5-year actuarial revision-free for AUS total device was 51%. Patients for primary implant for radiation were not more likely to experience revision than non-radiation patients. Preservation of erections was reported in half of the potent patients. Conclusions Transcorporal AUS cuff placement is a useful alternative procedure option for severe male UI treatment, especially in patients with a compromised urethra after prior surgery or radiation. A high continence rate was reported and implantation as first option in radiation patients should be considered.

The impact of trainee involvement on outcomes in low-dose-rate brachytherapy for prostate cancer.

PURPOSE: To determine the impact of fellow, resident, or medical student (MS) involvement on outcomes in patients undergoing permanent (125)I prostate seed implant. METHODS AND MATERIALS: The study population consisted of men with clinically localized low/intermediate-risk prostate cancer treated with low-dose-rate permanent interstitial brachytherapy. Cases were stratified according to resident, fellow, MS, or attending involvement. Outcomes were compared using analysis of variance, logistic regression, and log rank tests. RESULTS: A total of 291 patients were evaluated. Fellows, residents, and MS were involved in 47 (16.2%), 231 (79.4%), and 34 (11.7%) cases, respectively. Thirteen (4.4%) cases were completed by an attending physician alone. There was no difference in freedom from biochemical failure when comparing the resident, fellow, or attending alone groups (p = 0.10). There was no difference in V100 (volume of the prostate receiving 100% of the prescription dose) outcomes when comparing resident cases to fellow cases (p = 0.72) or attending alone cases (p = 0.78). There was no difference in D90 (minimum dose covering 90% of the postimplant volume) outcomes when comparing resident cases to fellow cases (p = 0.74) or attending alone cases (p = 0.58). When examining treatment toxicity, fellow cases had higher rates of acute Grade 2 + GU toxicity (p = 0.028). With the exception of higher urethra D90 among PGY 2-3 cases (p = 0.02), dosimetric outcomes were similar to cases with PGY 4-5 resident participation. There was no difference in outcomes for cases with and without MS participation. CONCLUSIONS: Interstitial prostate seed implants can be safely performed by trainees with appropriate supervision. Hands-on brachytherapy training is effective and feasible for trainees.

Dosimetry Modeling for Focal Low-Dose-Rate Prostate Brachytherapy.

PURPOSE: Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA). METHODS AND MATERIALS: Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focal (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations. RESULTS: WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm(3) was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types. CONCLUSIONS: Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a notable reduction to organs at risk. Treating smaller targets makes seed positioning more critical.

Quantifying the effect of seed orientation in postplanning dosimetry of low-dose-rate prostate brachytherapy.

PURPOSE: Radioactive seed orientations are usually ignored in clinical brachytherapy dosimetry for prostate implants. Associated with the anisotropic dose distribution of seeds, these orientations could cause dose differences between the planning configurations and the clinical postplanning dosimetry. This study will quantify the impact of seed orientation on the dosimetry. METHODS: 3D seed positions and θ and φ polar angles were obtained using five independent fluoroscopic images for 287 patients. Five dose calculation methods are compared: TG43-1D (1), TG43-2D parallel to implant axis (2) and with orientations (3), Monte Carlo (MC) simulations parallel (4), and MC simulations with orientations (5). GEANT4 v4.9.6 MC simulations were made in 1 mm(3) voxelized geometries based on the DICOM-RT information. Materials were assigned using thresholds based on the HU number, as recommended in TG186 reports. Seed voxels are overridden with prostatic materials and the layered mass geometry [Enger et al., Phys. Med. Biol. 57(19), 6269-6277 (2012)] allows subsequent placement of the source geometry. 500 million histories were used per patient. 3D dose and DVHs for each structure were calculated. RESULTS: The various seed orientations do not result in statistically significant differences on the dose metrics for the clinical target volume (CTV) or the urethra, based on the Student t-test p-value. Difference as low as -0.238% and 0.059% has been seen on the CTV D90, respectively, for the MC and the TG43. The difference between parallel and oriented calculations for the organs at risk (OARs) can differ by 2% on average. CONCLUSIONS: Based on the results from this study, seed orientations have no significant impact of CTV and urethra dose metrics but can affect OARs that are external to the CTV.

Tissue composition and density impact on the clinical parameters for (125)I prostate implants dosimetry.

The MCNPX code was used to calculate the TG-43U1 recommended parameters in water and prostate tissue in order to quantify the dosimetric impact in 30 patients treated with (125)I prostate implants when replacing the TG-43U1 formalism parameters calculated in water by a prostate-like medium in the planning system (PS) and to evaluate the uncertainties associated with Monte Carlo (MC) calculations. The prostate density was obtained from the CT of 100 patients with prostate cancer. The deviations between our results for water and the TG-43U1 consensus dataset values were -2.6% for prostate V100, -13.0% for V150, and -5.8% for D90; -2.0% for rectum V100, and -5.1% for D0.1; -5.0% for urethra D10, and -5.1% for D30. The same differences between our water and prostate results were all under 0.3%. Uncertainties estimations were up to 2.9% for the gL(r) function, 13.4% for the F(r,θ) function and 7.0% for Λ, mainly due to seed geometry uncertainties. Uncertainties in extracting the TG-43U1 parameters in the MC simulations as well as in the literature comparison are of the same order of magnitude as the differences between dose distributions computed for water and prostate-like medium. The selection of the parameters for the PS should be done carefully, as it may considerably affect the dose distributions. The seeds internal geometry uncertainties are a major limiting factor in the MC parameters deduction.

Dosimetry modeling for focal high-dose-rate prostate brachytherapy.

PURPOSE: The dosimetry of focal high-dose-rate prostate brachytherapy was assessed. Dose volume histogram parameters, robustness to source position errors, and Monte Carlo (MC) simulations were compared for whole-gland (WG), hemi-gland (HEMI), and ultra-focal (UF) treatment plans. METHODS AND MATERIALS: Tumor volumes were delineated based on MRI and template biopsy results for 9 patients. WG, HEMI, and UF plans were produced assuming 19 Gy single fraction monotherapy treatments. For UF plans, a 6-mm margin was applied to the visible tumor to create a focal-planning target volume (F-PTV). Systematic source position shifts of 1-4 mm were applied to assess plan robustness. The dosimetric impact of steel catheters was assessed using MC simulation. RESULTS: Mean D90 and V100 were 20.4 Gy and 97.9% for prostate in WG plans, 22.2 Gy and 98.1% for hemi-prostate in HEMI plans, and 23.0 Gy and 98.2% for F-PTV in UF plans. Mean urethra D10 was 20.3, 19.7, and 9.2 Gy in WG, HEMI, and UF plans, respectively. Mean rectal D2cc was 12.5, 9.8, and 4.6 Gy in WG, HEMI, and UF plans, respectively. Focal treatment plans were sensitive to source position errors-2 mm systematic shifts reduced mean prostate D90 by 0.7%, hemi-prostate D90 by 2.6%, and F-PTV D90 by 8.3% in WG, HEMI, and UF plans, respectively. MC simulation results were similar for all plan types with most dose volume histogram parameters reduced by <2%. CONCLUSIONS: HEMI and UF treatments can achieve higher D90 values compared with WG treatments with reduced organ at risk dose. Focal treatments are more sensitive to systematic source position errors than WG treatments.

Investigation of interseed attenuation and tissue composition effects in (125)I seed implant prostate brachytherapy.

PURPOSE: To use Monte Carlo (MC) simulation and sector analysis to assess interseed attenuation and scatter (ISA) and tissue effects in permanent seed implant prostate brachytherapy and to compare methods for modeling tissue. METHODS AND MATERIALS: CT-based postimplant plan simulations for 40 patients were evaluated using dose-volume histogram (DVH) parameters and sector analysis. Simulations in water (to evaluate ISA alone) and tissue assigned from contours or CT data, with and without calcifications, were compared. RESULTS: For patients without calcifications, mean combined ISA and tissue effect reduced prostate D90 by 4.2 Gy (2.9%), prostate V100 by 0.5 cm(3) (1.4%), urethra D10 by 8.6 Gy (3.5%), rectal [Formula: see text] by 11.6 Gy (10.5%), and the 100% isodose volume by 4.7 cm(3). Larger differences were observed comparing planned dose to postimplant, mean prostate D90 reduced from 185 to 149.8 Gy (-19%). For patients with calcifications, larger tissue effects were observed, prostate D90 reduced by up to 7.4%. Sector analysis showed dose reductions were larger in anterior and base sectors of the prostate. For patients without calcifications, contour- and CT-based tissue model results agreed within <0.5% for all DVH parameters, with up to 4% difference for patients with calcifications. CONCLUSIONS: Advanced brachytherapy dose calculation methods that take account of ISA and tissue effects show that clinical (125)I implant dose is different from TG-43U1 (AAPM Task Group No. 43 Report-Update 1) calculations, reducing DVH parameter values particularly for patients with calcifications. Peripheral dose and areas of the implant with relatively poorer coverage are particularly affected. However, dose reductions are small compared with other postimplant dose uncertainties.

Interstitial rotating shield brachytherapy for prostate cancer.

PURPOSE: To present a novel needle, catheter, and radiation source system for interstitial rotating shield brachytherapy (I-RSBT) of the prostate. I-RSBT is a promising technique for reducing urethra, rectum, and bladder dose relative to conventional interstitial high-dose-rate brachytherapy (HDR-BT). METHODS: A wire-mounted 62 GBq(153)Gd source is proposed with an encapsulated diameter of 0.59 mm, active diameter of 0.44 mm, and active length of 10 mm. A concept model I-RSBT needle/catheter pair was constructed using concentric 50 and 75 µm thick nickel-titanium alloy (nitinol) tubes. The needle is 16-gauge (1.651 mm) in outer diameter and the catheter contains a 535 µm thick platinum shield. I-RSBT and conventional HDR-BT treatment plans for a prostate cancer patient were generated based on Monte Carlo dose calculations. In order to minimize urethral dose, urethral dose gradient volumes within 0-5 mm of the urethra surface were allowed to receive doses less than the prescribed dose of 100%. RESULTS: The platinum shield reduced the dose rate on the shielded side of the source at 1 cm off-axis to 6.4% of the dose rate on the unshielded side. For the case considered, for the same minimum dose to the hottest 98% of the clinical target volume (D(98%)), I-RSBT reduced urethral D(0.1cc) below that of conventional HDR-BT by 29%, 33%, 38%, and 44% for urethral dose gradient volumes within 0, 1, 3, and 5 mm of the urethra surface, respectively. Percentages are expressed relative to the prescription dose of 100%. For the case considered, for the same urethral dose gradient volumes, rectum D(1cc) was reduced by 7%, 6%, 6%, and 6%, respectively, and bladder D(1cc) was reduced by 4%, 5%, 5%, and 6%, respectively. Treatment time to deliver 20 Gy with I-RSBT was 154 min with ten 62 GBq (153)Gd sources. CONCLUSIONS: For the case considered, the proposed(153)Gd-based I-RSBT system has the potential to lower the urethral dose relative to HDR-BT by 29%-44% if the clinician allows a urethral dose gradient volume of 0-5 mm around the urethra to receive a dose below the prescription. A multisource approach is necessary in order to deliver the proposed (153)Gd-based I-RSBT technique in reasonable treatment times.

Postimplant dosimetry using a Monte Carlo dose calculation engine: a new clinical standard.

PURPOSE: To use the Monte Carlo (MC) method as a dose calculation engine for postimplant dosimetry. To compare the results with clinically approved data for a sample of 28 patients. Two effects not taken into account by the clinical calculation, interseed attenuation and tissue composition, are being specifically investigated. METHODS AND MATERIALS: An automated MC program was developed. The dose distributions were calculated for the target volume and organs at risk (OAR) for 28 patients. Additional MC techniques were developed to focus specifically on the interseed attenuation and tissue effects. RESULTS: For the clinical target volume (CTV) D(90) parameter, the mean difference between the clinical technique and the complete MC method is 10.7 Gy, with cases reaching up to 17 Gy. For all cases, the clinical technique overestimates the deposited dose in the CTV. This overestimation is mainly from a combination of two effects: the interseed attenuation (average, 6.8 Gy) and tissue composition (average, 4.1 Gy). The deposited dose in the OARs is also overestimated in the clinical calculation. CONCLUSIONS: The clinical technique systematically overestimates the deposited dose in the prostate and in the OARs. To reduce this systematic inaccuracy, the MC method should be considered in establishing a new standard for clinical postimplant dosimetry and dose-outcome studies in a near future.