Dosimetric comparison of two treatment planning systems for spine SBRT.

Two commonly used treatment planning systems (TPS) are compared for the planning of spine stereotactic body radiotherapy (SBRT). The main purpose is to highlight relative advantages and disadvantages of each system and propose a methodologic approach for comparisons. Twenty clinical plans were inversely planned with step-and-shoot intensity-modulated radiotherapy (IMRT) each using 9 to 11 beams, referred to as IMRT_P. The prescription dose was 24 Gy in 2 fractions, and the plans were generated following our institutional protocol using the Pinnacle3 v9.2. Each case was replanned using a 2-arc volumetric modulated arc therapy (VMAT) approach, referred as VMAT_P. CT and structure sets were DICOM exported to Monaco v5.10 and planned in 2 different ways: IMRT (IMRT_M) and VMAT (VMAT_M) using the same prescription dose. Dose volume histograms (DVH) and other dose statistics of planning target volumes (PTV) and organ-at-risk (OAR) were analyzed and compared between plans. The gradient index (GI = ratio of 50% isodose volume to prescribed isodose volume) was used to measure dose fall-off outside of the PTV. Another metric - Gradient Index Inner (GIinner = the rate (in Gy/mm) - at which the dose changes from the level of the spinal cord/thecal sac toward the prescription dose) was developed and compared. All plans were considered clinically acceptable by institutional guidelines and achieved all of the OAR dose constraints. VMAT_M and IMRT_M showed comparable dose statistics for the PTV when compared to VMAT_P and IMRT_P, respectively. For IMRT plans, the median GIinner was 1.88 Gy/mm vs 1.52 Gy/mm for IMRT_M and IMRT_P respectively (p< 0.001). All other IMRT metrics were statistically similar except for the PTV maximum dose (Dmax), which was higher for IMRT_M than IMRT_P (median 30.7 Gy vs 29.0 Gy, p< 0.001). For VMAT plans, only PTV Dmin showed a statistical different between VMAT_M and VMAT_P of median 12.7 Gy vs 9.7 Gy (p< 0.001). In terms of beam sequencing parameters, the number of monitor units was statistically higher for VMAT_P compared to VMAT_M (median = 6764 vs 5376) whereas the number of segments for IMRT_M was statistically greater than IMRT_P (median = 155 vs 73). We were able to generate clinically acceptable plans for different types of spine SBRT using 2 different TPS. We used an evaluation strategy involving coverage, conformity, and dose gradient that can compared between TPS.

Monte Carlo simulation of radiation transport and dose deposition from locally released gold nanoparticles labeled with 111In, 177Lu or 90Y incorporated into tissue implantable depots.

Permanent seed implantation (PSI) brachytherapy is a highly conformal form of radiation therapy but is challenged with dose inhomogeneity due to its utilization of low energy radiation sources. Gold nanoparticles (AuNP) conjugated with electron emitting radionuclides have recently been developed as a novel form of brachytherapy and can aid in homogenizing dose through physical distribution of radiolabeled AuNP when injected intratumorally (IT) in suspension. However, the distribution is unpredictable and precise placement of many injections would be difficult. Previously, we reported the design of a nanoparticle depot (NPD) that can be implanted using PSI techniques and which facilitates controlled release of AuNP. We report here the 3D dose distribution resulting from a NPD incorporating AuNP labeled with electron emitters (90Y, 177Lu, 111In) of different energies using Monte Carlo based voxel level dosimetry. The MCNP5 Monte Carlo radiation transport code was used to assess differences in dose distribution from simulated NPD and conventional brachytherapy sources, positioned in breast tissue simulating material. We further compare these dose distributions in mice bearing subcutaneous human breast cancer xenografts implanted with 177Lu-AuNP NPD, or injected IT with 177Lu-AuNP in suspension. The radioactivity distributions were derived from registered SPECT/CT images and time-dependent dose was estimated. Results demonstrated that the dose distribution from NPD reduced the maximum dose 3-fold when compared to conventional seeds. For simulated NPD, as well as NPD implanted in vivo, 90Y delivered the most homogeneous dose distribution. The tumor radioactivity in mice IT injected with 177Lu-AuNP redistributed while radioactivity in the NPD remained confined to the implant site. The dose distribution from radiolabeled AuNP NPD were predictable and concentric in contrast to IT injected radiolabeled AuNP, which provided irregular and temporally variant dose distributions. The use of NPD may serve as an intermediate between PSI and radiation delivered by radiolabeled AuNP by providing a controlled method to improve delivery of prescribed doses as well as homogenize dose from low penetrating electron sources.

Direction modulated brachytherapy (DMBT) for treatment of cervical cancer: A planning study with 192 Ir, 60 Co, and 169 Yb HDR sources.

PURPOSE: To evaluate plan quality of a novel MRI-compatible direction modulated brachytherapy (DMBT) tandem applicator using 192 Ir, 60 Co, and 169 Yb HDR brachytherapy sources, for various cervical cancer high-risk clinical target volumes (CTVHR ). MATERIALS AND METHODS: The novel DMBT tandem applicator has six peripheral grooves of 1.3-mm diameter along a 5.4-mm thick nonmagnetic tungsten alloy rod. Monte Carlo (MC) simulations were used to benchmark the dosimetric parameters of the 192 Ir, 60 Co, and 169 Yb HDR sources in a water phantom against the literature data. 45 clinical cases that were treated using conventional tandem-and-ring applicators with 192 Ir source (192 Ir-T&R) were selected consecutively from intErnational MRI-guided BRAchytherapy in CErvical cancer (EMBRACE) trial. Then, for each clinical case, 3D dose distribution of each source inside the DMBT and conventional applicators were calculated and imported onto an in-house developed inverse planning optimization code to generate optimal plans. All plans generated by the DMBT tandem-and-ring (DMBT T&R) from all three sources were compared to the respective 192 Ir-T&R plans. For consistency, all plans were normalized to the same CTVHR D90 achieved in clinical plans. The D2 cm3 for organs at risk (OAR) such as bladder, rectum, and sigmoid, and D90, D98, D10, V100, and V200 for CTVHR were calculated. RESULTS: In general, plan quality significantly improved when a conventional tandem (Con.T) is replaced with the DMBT tandem. The target coverage metrics were similar across 192 Ir-T&R and DMBT T&R plans with all three sources (P > 0.093). 60 Co-DMBT T&R generated greater hot spots and less dose homogeneity in the target volumes compared with the 192 Ir- and 169 Yb-DMBT T&R plans. Mean OAR doses in the DMBT T&R plans were significantly smaller (P < 0.0084) than the 192 Ir-T&R plans. Mean bladder D2 cm3 was reduced by 4.07%, 4.15%, and 5.13%, for the 192 Ir-, 60 Co-, and 169 Yb-DMBT T&R plans respectively. Mean rectum (sigmoid) D2 cm3 was reduced by 3.17% (3.63%), 2.57% (3.96%), and 4.65% (4.34%) for the 192 Ir-, 60 Co-, and 169 Yb-DMBT T&R plans respectively. The DMBT T&R plans with the 169 Yb source generally resulted in the greatest OAR sparing when the CTVHR were larger and irregular in shape, while for smaller and regularly shaped CTVHR (<30 cm3 ), OAR sparing between the sources were comparable. CONCLUSIONS: The DMBT tandem provides a promising alternative to the Con.T design with significant improvement in the plan quality for various target volumes. The DMBT T&R plans generated with the three sources of varying energies generated superior plans compared to the conventional T&R applicators. Plans generated with the 169 Yb-DMBT T&R produced best results for larger and irregularly shaped CTVHR in terms of OAR sparing. Thus, this study suggests that the combination of the DMBT tandem applicator with varying energy sources can work synergistically to generate improved plans for cervical cancer brachytherapy.

Depot system for controlled release of gold nanoparticles with precise intratumoral placement by permanent brachytherapy seed implantation (PSI) techniques.

We report the design of a nanoparticle depot (NPD) system for local delivery of gold nanoparticles (AuNP) that facilitates their controlled release and is implantable into tumors by permanent seed implantation (PSI) brachytherapy techniques. Various sizes (5, 15, 30, and 50nm) of polyethylene glycol (PEG) coated AuNP and concentrations (6%, 8%, and 10% w/v) of calcium alginate used to form the NPD were studied. AuNP release rate, diffusion characteristics and spatial distribution were characterized in a tissue equivalent phantom model, and in a breast cancer tumor xenograft model and compared to a Fickian diffusion computational model, to identify the optimal NPD composition. In phantoms, 5nm and 15nm AuNP were released more rapidly than 30nm or 50nm AuNP but when implanted into tumor xenografts, AuNP exhibited slower release from NPD. Controlled prolonged release of AuNP was observed in tumor tissue over durations which were dependent on AuNP size. Maximum release and distribution in tumors were achieved using 5nm AuNP incorporated into the NPD. These results demonstrate the potential for the NPD as an effective local delivery system for AuNP-based therapies.

Sensitivity of clinically relevant dosimetric parameters to contouring uncertainty in postimplant dosimetry of low-dose-rate prostate permanent seed brachytherapy.

PURPOSE: There is strong evidence relating postimplant dosimetry for low-dose-rate prostate seed brachytherapy to local control rates. The delineation of the prostate on CT images, however, represents a challenge due to the lack of soft-tissue contrast to identify the prostate borders. This study aims at quantifying the sensitivity of prostate V100 and D90 to contouring uncertainty as clinically relevant parameters for evaluation of target coverage in postimplant dosimetry. METHODS AND MATERIALS: CT images, postoperative plans, and contours of a cohort of patients (n = 43; low risk = 55.8%, intermediate risk = 39.5%, high risk = 4.7%), who had received prostate seed brachytherapy, were imported into MIM Symphony treatment planning system. The prostate contours in postimplant CT images were expanded or contracted uniformly in extents of ±1.00 mm, ±2.00 mm, ±3.00 mm, ±4.00 mm, and ±5.00 mm. The values for V100 and D90 were extracted from dose-volume histograms for each contour and compared. RESULTS: Significant changes were observed in the values of D90 and V100 as well as the number of inacceptable plans for expansion or contraction of only few millimeters. Evaluation of a plan coverage based on D90 was found to be less sensitive to systematic contouring errors compared with V100. Number of plans incorrectly identified for lack or adequacy of coverage is lower using D90 compared with V100 for the same margin of error. CONCLUSIONS: Evaluation of a plan coverage based on V100 is too sensitive to systematic contouring errors of prostate. D90 increases the accuracy of CT-based postimplant quality assurance in identifying plans with insufficient coverage compared with V100.

Quantitative MRI assessment of a novel direction modulated brachytherapy tandem applicator for cervical cancer at 1.5T.

BACKGROUND AND PURPOSE: The purpose of this work is to quantitatively investigate the artifacts and image distortions induced in the MR images by a recently proposed direction modulated brachytherapy (DMBT) tandem applicator prototype. This new MRI-compatible applicator allows better sparing of organs-at-risk (OAR) for cervical cancer patients, while providing conformal dose distributions to target volumes. MATERIALS AND METHODS: Specific phantom and tools were designed and manufactured for this study. The phantom was filled with a tissue-like solution and MR images were acquired with clinical protocols as per GEC-ESTRO recommendations. Images were obtained at 6 different orientations that mimic possible clinical settings and full-width-at-half-maximum (FWHM) was recorded at multiple locations/angles. The accuracy of detecting the centerline of the tandem was assessed using a novel radial-fiducials mount. RESULTS: FWHM from all line profiles at all angles and all orientations was 6.14±0.7mm (compared to 6mm of the actual DMBT tandem diameter). The in-plane spatial-shift observed at para-axial and para-sagittal views was less than 0.5mm. CONCLUSIONS: This work demonstrated that the novel DMBT tandem applicator prototype has minimal artifact in T2-weighted images employed in clinical practice, suggesting the applicator might be a good candidate for MRI-guided adaptive brachytherapy.

Clinical Significance of Accounting for Tissue Heterogeneity in Permanent Breast Seed Implant Brachytherapy Planning.

PURPOSE: The inhomogeneity correction factor (ICF) method provides heterogeneity correction for the fast calculation TG43 formalism in seed brachytherapy. This study compared ICF-corrected plans to their standard TG43 counterparts, looking at their capacity to assess inadequate coverage and/or risk of any skin toxicities for patients who received permanent breast seed implant (PBSI). METHODS AND MATERIALS: Two-month postimplant computed tomography scans and plans of 140 PBSI patients were used to calculate dose distributions by using the TG43 and the ICF methods. Multiple dose-volume histogram (DVH) parameters of clinical target volume (CTV) and skin were extracted and compared for both ICF and TG43 dose distributions. Short-term (desquamation and erythema) and long-term (telangiectasia) skin toxicity data were available on 125 and 110 of the patients, respectively, at the time of the study. The predictive value of each DVH parameter of skin was evaluated using the area under the receiver operating characteristic (ROC) curve for each toxicity endpoint. RESULTS: Dose-volume histogram parameters of CTV, calculated using the ICF method, showed an overall decrease compared to TG43, whereas those of skin showed an increase, confirming previously reported findings of the impact of heterogeneity with low-energy sources. The ICF methodology enabled us to distinguish patients for whom the CTV V100 and V90 are up to 19% lower compared to TG43, which could present a risk of recurrence not detected when heterogeneity are not accounted for. The ICF method also led to an increase in the prediction of desquamation, erythema, and telangiectasia for 91% of skin DVH parameters studied. CONCLUSIONS: The ICF methodology has the advantage of distinguishing any inadequate dose coverage of CTV due to breast heterogeneity, which can be missed by TG43. Use of ICF correction also led to an increase in prediction accuracy of skin toxicities in most cases.

A dosimetric study of cardiac dose sparing using the reverse semi-decubitus technique for left breast and internal mammary chain irradiation.

BACKGROUND AND PURPOSE: Breath-hold techniques can reduce cardiac dose in breast radiotherapy. The reverse semi-decubitus (RSD) technique is an alternative free-breathing method used at our centre. This study compares the dosimetry of free-breathing supine, RSD and moderate deep inspiration breath-hold (mDIBH) techniques. MATERIALS AND METHODS: Twelve patients with left-sided breast cancer who were simulated using standard supine, RSD and mDIBH techniques were identified retrospectively. New plans using standard breast tangents and techniques for internal mammary chain (IMC) nodal coverage were assessed. RESULTS: Using standard tangents, mean heart dose, heart V25Gy and mean left anterior descending artery (LAD) dose were found to be significantly lower for RSD and mDIBH when compared to free-breathing supine (p ⩽ 0.03). Using wide-tangents, the maximum LAD point dose was also lower for RSD and mDIBH (p ⩽ 0.02). There were no statistically significant dosimetric differences found between the RSD and mDIBH simulation techniques for standard breast-tangent plans, though organ-at-risk doses were lower for mDIBH in wide-tangent plans. There was no improvement in cardiac dosimetry between RSD and free-breathing supine when using an electron field IMC plan. CONCLUSIONS: For patients unable to tolerate breath-hold, the RSD technique is an alternative approach that can reduce cardiac dose.

Measurement of mean cardiac dose for various breast irradiation techniques and corresponding risk of major cardiovascular event.

After breast conserving surgery, early stage breast cancer patients are currently treated with a wide range of radiation techniques including whole breast irradiation (WBI), accelerated partial breast irradiation (APBI) using high-dose rate (HDR) brachytherapy, or 3D-conformal radiotherapy (3D-CRT). This study compares the mean heart's doses for a left breast irradiated with different breast techniques. An anthropomorphic Rando phantom was modified with gelatin-based breast of different sizes and tumors located medially or laterally. The breasts were treated with WBI, 3D-CRT, or HDR APBI. The heart's mean doses were measured with Gafchromic films and controlled with optically stimulated luminescent dosimeters. Following the model reported by Darby (1), major cardiac were estimated assuming a linear risk increase with the mean dose to the heart of 7.4% per gray. WBI lead to the highest mean heart dose (2.99 Gy) compared to 3D-CRT APBI (0.51 Gy), multicatheter (1.58 Gy), and balloon HDR (2.17 Gy) for a medially located tumor. This translated into long-term coronary event increases of 22, 3.8, 11.7, and 16% respectively. The sensitivity analysis showed that the tumor location had almost no effect on the mean heart dose for 3D-CRT APBI and a minimal impact for HDR APBI. In case of WBI large breast size and set-up errors lead to sharp increases of the mean heart dose. Its value reached 10.79 Gy for women with large breast and a set-up error of 1.5 cm. Such a high value could increase the risk of having long-term coronary events by 80%. Comparison among different irradiation techniques demonstrates that 3D-CRT APBI appears to be the safest one with less probability of having cardiovascular events in the future. A sensitivity analysis showed that WBI is the most challenging technique for patients with large breasts or when significant set-up errors are anticipated. In those cases, additional heart shielding techniques are required.

A simplified analytical dose calculation algorithm accounting for tissue heterogeneity for low-energy brachytherapy sources.

The American Association of Physicists in Medicine Task Group No. 43 (AAPM TG-43) formalism is the standard for seeds brachytherapy dose calculation. But for breast seed implants, Monte Carlo simulations reveal large errors due to tissue heterogeneity. Since TG-43 includes several factors to account for source geometry, anisotropy and strength, we propose an additional correction factor, called the inhomogeneity correction factor (ICF), accounting for tissue heterogeneity for Pd-103 brachytherapy. This correction factor is calculated as a function of the media linear attenuation coefficient and mass energy absorption coefficient, and it is independent of the source internal structure. Ultimately the dose in heterogeneous media can be calculated as a product of dose in water as calculated by TG-43 protocol times the ICF. To validate the ICF methodology, dose absorbed in spherical phantoms with large tissue heterogeneities was compared using the TG-43 formalism corrected for heterogeneity versus Monte Carlo simulations. The agreement between Monte Carlo simulations and the ICF method remained within 5% in soft tissues up to several centimeters from a Pd-103 source. Compared to Monte Carlo, the ICF methods can easily be integrated into a clinical treatment planning system and it does not require the detailed internal structure of the source or the photon phase-space.