Clinical utility and value contribution of an MRI-positive line marker for image-guided brachytherapy in gynecologic malignancies.

PURPOSE: The purpose of this study was to investigate the utility of a novel MRI-positive line marker, composed of C4:S (cobalt chloride-based contrast agent) encapsulated in high-density polyethylene tubing, in permitting dosimetry and treatment planning directly on MRI. METHODS AND MATERIALS: We evaluated the clinical feasibility of the C4:S line markers in nine sequential brachytherapy procedures for gynecologic malignancies, including six tandem-and-ovoid and three interstitial cases. We then quantified the internal resource utilization of an intraoperative MRI-guided procedural episode via time-driven activity-based costing, identifying opportunities for cost-containment with use of the C4:S line markers. RESULTS: The C4:S line markers demonstrated the strongest positive signal visibility on 3D constructive interference in steady state (CISS)/FIESTA-C followed by T1-weighted sequences, permitting accurate delineation of the applicator lumen and thus the source path. These images may be fused along with traditional T2-weighted sequences for optimal tumor and anatomy contouring, followed by treatment planning directly on MRI. By eliminating postoperative CT for fusion and applicator registration from the procedural episode, use of the C4:S line markers could decrease workflow time and lower total delivery costs per procedure. CONCLUSIONS: This analysis supports the clinical utility and value contribution of the C4:S line markers, which permit accurate MRI-based dosimetry and treatment planning, thereby eliminating the need for postoperative CT for fusion and applicator registration.

Quantifying institutional resource utilization of adjuvant brachytherapy and intensity-modulated radiation therapy for endometrial cancer via time-driven activity-based costing.

PURPOSE: The purpose of this study was to quantify the cost of resources required to deliver adjuvant radiation therapy (RT) for high- to intermediate-risk endometrial cancer using time-driven activity-based costing (TDABC). METHODS AND MATERIALS: Comparisons were made for three and five fractions of vaginal cuff brachytherapy (VCB), 28 fractions of intensity-modulated radiation therapy (IMRT), and combined modality RT (25-fraction IMRT followed by 2-fraction VCB). Process maps were developed representing each phase of care. Salary and equipment costs were obtained to derive capacity cost rates, which were multiplied by process times and summed to calculate total costs. Costs were compared with 2018 Medicare physician fee schedule reimbursement. RESULTS: Full cycle costs for 5-fraction VCB, IMRT, and combined modality RT were 42%, 61%, and 93% higher, respectively, than for 3-fraction VCB. Differences were attributable to course duration and number of fractions/visits. Accumulation of cost throughout the cycle was steeper for VCB, rising rapidly within a shorter time frame. Personnel cost was the greatest driver for all modalities, constituting 76% and 71% of costs for IMRT and VCB, respectively, with VCB requiring 74% more physicist time. Total reimbursement for 5-fraction VCB was 40% higher than for 3-fractions. Professional reimbursement for IMRT was 31% higher than for 5-fraction VCB, vs. IMRT requiring 43% more physician TDABC than 5-fraction VCB. CONCLUSIONS: TDABC is a feasible methodology to quantify the cost of resources required for delivery of adjuvant IMRT and brachytherapy and produces directionally accurate costing data as compared with reimbursement calculations. Such data can inform institution-specific financial analyses, resource allocation, and operational workflows.

Interstitial Brachytherapy for the Treatment of Locally Recurrent Anorectal Cancer.

BACKGROUND: Local tumor control (LC), overall survival (OS), symptom palliation, and late toxicity for patients with locally recurrent anorectal cancer treated with a computed tomography (CT)-guided interstitial brachytherapy implant were examined. METHODS: The medical records of 20 consecutive patients who had received interstitial brachytherapy for locally recurrent anorectal cancer from 2000 through 2012 were reviewed. Seventeen patients (85 %) had rectal cancer and three had anal cancer [median follow-up time for living patients, 23 months (range 13-132)]. Brachytherapy was used most commonly at the second pelvic recurrence (n = 13, 65 %). The implant dose was prescribed to 80 Gy to a 1-cm margin or 120 Gy to 100 % of the gross tumor volume. Endpoints were OS, LC, toxicity, and symptom palliation rate, all calculated from the time of implant. RESULTS: The actuarial 1-year rates of LC and OS were 80 and 95 %, respectively. At presentation, 17 patients (85 %) had symptoms related to the treated tumor which were palliated in 13 patients (76 %) at a median time of 3 months (range 1-6); palliation was permanent for seven patients (54 %), and the other six patients lost palliation after a median 8 months (range 5-17). One patient experienced a grade 3 late complication requiring a stent for hydronephrosis; five had grade 2 toxicity, and four had grade 1 toxicity. CONCLUSIONS: CT-guided interstitial brachytherapy for locally recurrent anorectal tumors produced durable tumor control and long-term survival, with effective palliation and minimal long-term morbidity.

A choice of radionuclide: Comparative outcomes and toxicity of ruthenium-106 and iodine-125 in the definitive treatment of uveal melanoma.

PURPOSE: Both iodine-125 ((125)I) Collaborative Ocular Melanoma Study and ruthenium-106 ((106)Ru) eye plaques can achieve excellent tumor control in patients diagnosed with uveal melanoma. We analyzed our single institutional experience in the management of ocular melanoma treated with either (125)I or (106)Ru plaque brachytherapy. METHODS AND MATERIALS: The records of 107 patients with uveal melanoma treated with either (106)Ru (n = 40) or (125)I (n = 67) plaque brachytherapy between 2000 and 2008 were retrospectively reviewed. Tumor control parameters and toxicity were assessed. RESULTS: Actuarial 5-year rates of local control, progression-free survival, and overall survival with (106)Ru were 97%, 94%, and 92%, respectively. For (125)I, these values were 83%, 65%, and 80%. In the subset of patients with tumor apex height ≤5 mm (36 (125)I and 40 (106)Ru), there was no difference in overall survival; however, progression-free survival was significantly improved with (106)Ru (P = .02). Enucleation-free survival was significantly different between the 2 subsets, with no enucleations in the (106)Ru cohort (P = .02). Patients treated with (106)Ru experienced reduced retinopathy (P = .03) and cataracts (P < .01). CONCLUSIONS: Both (125)I and (106)Ru eye plaque brachytherapy treatment result in encouraging tumor control for patients with uveal melanoma. We demonstrate that (106)Ru offers these benefits with reduced toxicity in patients treated for uveal melanomas ≤5 mm in apical height.

Disease control and toxicity outcomes using ruthenium eye plaque brachytherapy in the treatment of uveal melanoma.

PURPOSE: Ruthenium-106 ((106)Ru) eye plaques have the potential to achieve excellent tumor control with acceptable radiation toxicity. We evaluated our experience in the management of uveal melanoma treated with (106)Ru brachytherapy. METHODS AND MATERIALS: The records of 40 patients with uveal melanoma treated with brachytherapy using (106)Ru plaques from 2003 to 2007 at University of Texas MD Anderson Cancer Center were reviewed. Endpoints assessed included tumor control and toxicity. RESULTS: Median ophthalmologic follow-up was 67 months. Actuarial 5-year rates of local control (LC), progression-free survival (PFS), and overall survival (OS) were 97%, 94%, and 92%. There were 3 deaths, 2 related to melanoma. Fifteen patients experienced clinically significant visual loss; no patients were diagnosed with neovascular glaucoma, and 1 patient developed a clinically significant radiation-associated cataract. No patient required enucleation. CONCLUSIONS: We report the largest published US cohort of patients treated with (106)Ru plaque brachytherapy for uveal melanoma. Tumor control was excellent, and toxicity was acceptably low. These data support the reintroduction of (106)Ru into clinical practice for ocular melanoma.

Variable impact of intracavitary brachytherapy fractionation schedule on biologically effective dose to organs at risk in patients with cervical cancer.

PURPOSE: To determine the effect of intracavitary brachytherapy (ICBT) fractionation schedule on biologically effective dose to organs at risk. METHODS AND MATERIALS: We reviewed records from 26 patients who had CT imaging during ICBT for International Federation of Gynecology and Obstetrics stage IB2-IVA cervical cancer. Using α/ß=10, we calculated hypothetical nominal doses to achieve a biologically effective dose at 2 Gy per fraction (EQD2α/ß=10) of 40 Gy to Point A for high-dose-rate ICBT with 1-15 fractions. Corresponding minimum EQD2α/ß=3s to the maximally irradiated 2 cc of rectum, bladder, and sigmoid were calculated for each fractionation scheme and added to EQD2α/ß=3 from external beam radiotherapy. Total EQD2α/ß=3s were compared with American Brachytherapy Society suggested dose constraints (rectum/sigmoid, ≤75 Gy; bladder, ≤90 Gy). RESULTS: Except for rectal EQD2α/ß=3 in three patients, the rectal, bladder, and sigmoid EQD2α/ß=3s decreased with increasing fractionation in all patients. Although the total rectal EQD2α/ß=3s were less than the American Brachytherapy Society rectal dose constraint in all patients at all fractionation schedules, the total bladder EQD2α/ß=3s routinely exceeded the bladder dose constraint, even at maximum fractionation. By contrast, increasing fractionation decreased the number of patients with doses exceeding the sigmoid dose constraint by 48%. CONCLUSIONS: The relationship between ICBT fractionation schedule and relative EQD2α/ß=3s to rectum, bladder, and sigmoid depends on individual anatomy. Fractionation optimization can improve therapeutic ratios by minimizing the risk or severity of toxic effects. For patients in whom many fractions optimize the therapeutic ratio, low-dose-rate or pulsed-dose-rate brachytherapy may be preferred.

Development and implementation of a remote audit tool for high dose rate (HDR) Ir-192 brachytherapy using optically stimulated luminescence dosimetry.

PURPOSE: The aim of this work was to create a mailable phantom with measurement accuracy suitable for Radiological Physics Center (RPC) audits of high dose-rate (HDR) brachytherapy sources at institutions participating in National Cancer Institute-funded cooperative clinical trials. Optically stimulated luminescence dosimeters (OSLDs) were chosen as the dosimeter to be used with the phantom. METHODS: The authors designed and built an 8 × 8 × 10 cm(3) prototype phantom that had two slots capable of holding Al2O3:C OSLDs (nanoDots; Landauer, Glenwood, IL) and a single channel capable of accepting all (192)Ir HDR brachytherapy sources in current clinical use in the United States. The authors irradiated the phantom with Nucletron and Varian (192)Ir HDR sources in order to determine correction factors for linearity with dose and the combined effects of irradiation energy and phantom characteristics. The phantom was then sent to eight institutions which volunteered to perform trial remote audits. RESULTS: The linearity correction factor was kL = (-9.43 × 10(-5) × dose) + 1.009, where dose is in cGy, which differed from that determined by the RPC for the same batch of dosimeters using (60)Co irradiation. Separate block correction factors were determined for current versions of both Nucletron and Varian (192)Ir HDR sources and these vendor-specific correction factors differed by almost 2.6%. For the Nucletron source, the correction factor was 1.026 [95% confidence interval (CI) = 1.023-1.028], and for the Varian source, it was 1.000 (95% CI = 0.995-1.005). Variations in lateral source positioning up to 0.8 mm and distal∕proximal source positioning up to 10 mm had minimal effect on dose measurement accuracy. The overall dose measurement uncertainty of the system was estimated to be 2.4% and 2.5% for the Nucletron and Varian sources, respectively (95% CI). This uncertainty was sufficient to establish a ± 5% acceptance criterion for source strength audits under a formal RPC audit program. Trial audits of four Nucletron sources and four Varian sources revealed an average RPC-to-institution dose ratio of 1.000 (standard deviation = 0.011). CONCLUSIONS: The authors have created an OSLD-based (192)Ir HDR brachytherapy source remote audit tool which offers sufficient dose measurement accuracy to allow the RPC to establish a remote audit program with a ± 5% acceptance criterion. The feasibility of the system has been demonstrated with eight trial audits to date.

Monte Carlo model for a prototype CT-compatible, anatomically adaptive, shielded intracavitary brachytherapy applicator for the treatment of cervical cancer.

PURPOSE: Current, clinically applicable intracavitary brachytherapy applicators that utilize shielded ovoids contain a pair of tungsten-alloy shields which serve to reduce dose delivered to the rectum and bladder during source afterloading. After applicator insertion, these fixed shields are not necessarily positioned to provide optimal shielding of these critical structures due to variations in patient anatomies. The authors present a dosimetric evaluation of a novel prototype intracavitary brachytherapy ovoid [anatomically adaptive applicator (A3)], featuring a single shield whose position can be adjusted with two degrees of freedom: Rotation about and translation along the long axis of the ovoid. METHODS: The dosimetry of the device for a HDR 192Ir was characterized using radiochromic film measurements for various shield orientations. A MCNPX Monte Carlo model was developed of the prototype ovoid and integrated with a previously validated model of a v2 mHDR 192Ir source (Nucletron Co.). The model was validated for three distinct shield orientations using film measurements. RESULTS: For the most complex case, 91% of the absolute simulated and measured dose points agreed within 2% or 2 mm and 96% agreed within 10% or 2 mm. CONCLUSIONS: Validation of the Monte Carlo model facilitates future investigations into any dosimetric advantages the use of the A3 may have over the current state of art with respect to optimization and customization of dose delivery as a function of patient anatomical geometries.

Retrospective dosimetric comparison of low-dose-rate and pulsed-dose-rate intracavitary brachytherapy using a tandem and mini-ovoids.

The purpose of this study was to compare the dose distribution of Iridium-192 ((192)Ir) pulsed-dose-rate (PDR) brachytherapy to that of Cesium-137 ((137)Cs) low-dose-rate (LDR) brachytherapy around mini-ovoids and an intrauterine tandem. Ten patient treatment plans were selected from our clinical database, all of which used mini-ovoids and an intrauterine tandem. A commercial treatment planning system using AAPM TG43 formalism was used to calculate the dose in water for both the (137)Cs and (192)Ir sources. For equivalent system loadings, we compared the dose distributions in relevant clinical planes, points A and B, and to the ICRU bladder and rectal reference points. The mean PDR doses to points A and B were 3% +/- 1% and 6% +/- 1% higher than the LDR doses, respectively. For the rectum point, the PDR dose was 4% +/- 3% lower than the LDR dose, mainly because of the (192)Ir PDR source anisotropy. For the bladder point, the PDR dose was 1% +/- 4% higher than the LDR dose. We conclude that the PDR and LDR dose distributions are equivalent for intracavitary brachytherapy with a tandem and mini-ovoids. These findings will aid in the transfer from the current practice of LDR intracavitary brachytherapy to PDR for the treatment of gynecologic cancers.

Comparison of dose distributions around the pulsed-dose-rate Fletcher-Williamson and the low-dose-rate Fletcher-Suit-Delclos ovoids: a Monte Carlo study.

We performed a Monte Carlo study to compare dose distributions for a Fletcher-Suit-Delclos (FSD) ovoid used with (137)Cs low-dose-rate (LDR) sources with those for a Fletcher-Williamson (FW) ovoid used with an (192)Ir pulsed-dose-rate (PDR) source for intracavitary brachytherapy of cervical cancer. We recently reported on extensive validation of Monte Carlo MCNPX models of these ovoids using radiochromic film measurements. Here, we compared these models assuming identical loading of 10, 15 and 20 mgRaEq (72, 108 and 145 cGy cm(2) h(-1), respectively) in three dose mesh planes: one perpendicular to the ovoid long axis bisecting the ovoid, one parallel to and displaced 2 cm medially from the long axis of the ovoid, and a 'rectal' plane perpendicular to the long axis located 1 cm distal to the distal face of the ovoid cap. The FW ovoid delivered slightly higher doses (within 10%) over all loadings to regions away from the bladder and rectal shields when compared to the FSD ovoid. However, the FW ovoid delivered much higher doses (>50%) in regions near these shields. In the rectal plane, the FW ovoid delivered a slightly higher dose, but within the region directly behind the rectal shield, the FW ovoid delivered a dose ranging from +35% to -35% of the FSD dose distribution. We attribute these differences to intrinsic differences in source characteristics (radial dose function and anisotropy factors) and extrinsic factors such as the solid-angle effect between sources and shields and applicator design.

Monte Carlo calculations of the dose distribution around a commercial gynecologic tandem applicator.

BACKGROUND AND PURPOSE: Dose rate distributions around Fletcher Suit Delclos (FSD) tandem applicators used for intracavitary brachytherapy are usually calculated by assuming each source is a point source and summing the contributions from each of the sources. Consequently, interpellet attenuation and scattering are ignored. Additional error may be introduced because the applicator walls and tip screw are not considered. The focus of this study was a Monte Carlo simulation of a Selectron tandem, verification of the calculations, and presentation of the implications of the point-source approximation for treatment planning. MATERIALS AND METHODS: MCNPX 2.4.k was used to calculate dose rate distributions around straight and curved tandems. The Monte Carlo calculations were verified with radiochromic film. RESULTS: MCNPX calculated dose to within +/-2% or +/-2 mm for 97% of the points on the film parallel to the long axis and 98% on a film perpendicular to the long axis of the straight portion of the tandem. The point source approximation overestimated dose by as much as 33% superior to the tip of the tandem as compared to MCNPX. The point source approximation overestimated dose when photons passed through multiple pellets by as much as 18% as compared to MCNPX. Laterally, the dose distribution was not affected greatly. CONCLUSIONS: Interpellet attenuation was a dominant factor in determining the distribution along the length of the pellet train. MCNPX calculated doses accurately when the pellets and applicator walls were included in the geometry. The point source approximation is adequate lateral to the tandem. The point source approximation does not calculate dose accurately superior to the tandem or when photons pass through multiple pellets.

Dosimetric evaluation of the Fletcher-Williamson ovoid for pulsed-dose-rate brachytherapy: a Monte Carlo study.

We used radiochromic film dosimetry to validate a Monte Carlo (MC) model of a 192Ir pulsed-dose-rate (PDR) source inside a Fletcher-Williamson ovoid. MD-55-2 radiochromic film was placed in a high-impact polystyrene phantom in a plane parallel to and displaced 2.0 cm medially from the long axis of the ovoid. MC N-particle transport code (MCNPX) version 2.4 was used to model the ovoid and the 192Ir source. Energy deposition was calculated using a track-length estimator modified by an energy-dependent heating function, which is a good approximation of the collision kerma. To convert the estimates of the MC dose per simulated particle to clinically relevant absolute dosimetry, additional MC models of an actual and a virtual 192Ir source in dry air were simulated to determine air kerma strength for the penetrating part of the photon spectrum (>11.3 keV). The absolute dose distributions predicted by MCNPX agreed with the film results and were within +/-9.4% (k = 2) and within +/-2% or within a distance to agreement of 2 mm for 94% of the dose grid. Additional MC models characterized the uncertainty resulting from source positioning inside the ovoid. For a worst-case scenario of 1 mm off centre from the nominal source position in the 3 mm diameter ovoid shaft, the average dose deviation over the film plane was +/-5% (1sigma = +/-4%), with maximum deviation near the sharp dose-gradient provided by the shields of -20% to + 26%. A validated MC model is the first requirement to simulate common LDR clinical loadings (5-20 mgRaEq) and, thus, will aid in the transition from the current 137Cs Selectron LDR ICBT to PDR for treatment of gynecologic cancers.

Comparison of Monte Carlo calculations around a Fletcher Suit Delclos ovoid with radiochromic film and normoxic polymer gel dosimetry.

The Fletcher Suit Delclos (FSD) ovoids employed in intracavitary brachytherapy (ICB) for cervical cancer contain shields to reduce dose to the bladder and rectum. Many treatment planning systems (TPS) do not include the shields and other ovoid structures in the dose calculation. Instead, TPSs calculate dose by summing the dose contributions from the individual sources and ignoring ovoid structures such as the shields. The goal of this work was to calculate the dose distribution with Monte Carlo around a Selectron FSD ovoid and compare these calculations with radiochromic film (RCF) and normoxic polymer gel dosimetry. Monte Carlo calculations were performed with MCNPX 2.5.c for a single Selectron FSD ovoid with and without shields. RCF measurements were performed in a plane parallel to and displaced laterally 1.25 cm from the long axis of the ovoid. MAGIC gel measurements were performed in a polymethylmethacrylate phantom. RCF and MAGIC gel were irradiated with four 33 microGy m2 h(-1) Cs-137 pellets for a period of 24 h. Results indicated that MCNPX calculated dose to within +/- 2% or 2 mm for 98% of points compared with RCF measurements and to within +/- 3% or 3 mm for 98% of points compared with MAGIC gel measurements. It is concluded that MCNPX 2.5.c can calculate dose accurately in the presence of the ovoid shields, that RCF and MAGIC gel can demonstrate the effect of ovoid shields on the dose distribution and the ovoid shields reduce the dose by as much as 50%.

Comparison of Monte Carlo calculations around a Fletcher Suit Delclos ovoid with radiochromic film and normoxic polymer gel dosimetry.

The Fletcher Suit Delclos (FSD) ovoids employed in intracavitary brachytherapy (ICB) for cervical cancer contain shields to reduce dose to the bladder and rectum. Many treatment planning systems (TPS) do not include the shields and other ovoid structures in the dose calculation. Instead, TPSs calculate dose by summing the dose contributions from the individual sources and ignoring ovoid structures such as the shields. The goal of this work was to calculate the dose distribution with Monte Carlo around a Selectron FSD ovoid and compare these calculations with radiochromic film (RCF) and normoxic polymer gel dosimetry. Monte Carlo calculations were performed with MCNPX 2.5.c for a single Selectron FSD ovoid with and without shields. RCF measurements were performed in a plane parallel to and displaced laterally 1.25 cm from the long axis of the ovoid. MAGIC gel measurements were performed in a polymethylmethacrylate phantom. RCF and MAGIC gel were irradiated with four 33µGym2h-1 Cs-137 pellets for a period of 24 h. Results indicated that MCNPX calculated dose to within ±2% or 2 mm for 98% of points compared with RCF measurements and to within ±3% or 3 mm for 98% of points compared with MAGIC gel measurements. It is concluded that MCNPX 2.5.c can calculate dose accurately in the presence of the ovoid shields, that RCF and MAGIC gel can demonstrate the effect of ovoid shields on the dose distribution and the ovoid shields reduce the dose by as much as 50%.