Shahram Mashouf

Implications on clinical scenario of gold nanoparticle radiosensitization in regards to photon energy, nanoparticle size, concentration and location

Gold nanoparticle (AuNP) radiosensitization represents a novel approach to enhance the effectiveness of ionizing radiation. Its efficiency varies widely with photon source energy and AuNP size, concentration, and intracellular localization. In this Monte Carlo study we explored the effects of those parameters to define the optimal clinical use of AuNPs. Photon sources included (103)Pd and (125)I brachytherapy seeds; (169)Yb, (192)Ir high dose rate sources, and external beam sources 300 kVp and 6 MV. AuNP sizes were 1.9, 5, 30, and 100 nm. We observed a 10(3) increase in the rate of photoelectric absorption using (125)I compared to 6 MV. For a (125)I source, to double the dose requires concentrations of 5.33-6.26 mg g(-1) of Au or 7.10 × 10(4) 30 nm AuNPs per tumor cell. For 6 MV, concentrations of 1560-1760 mg g(-1) or 2.17 × 10(7) 30 nm AuNPs per cell are needed, which is not clinically achievable. Examining the proportion of energy transferred to escaping particles or internally absorbed in the nanoparticle suggests two clinical strategies: the first uses photon energies below the k-edge and takes advantage of the extremely localized Auger cascade. It requires small AuNPs conjugated to tumor targeted moieties and nuclear localizing sequences. The second, using photon sources above the k-edge, requires a higher gold concentration in the tumor region. In this approach, energy deposited by photoelectrons is the main contribution to radiosensitization; AuNP size and cellular localization are less relevant.

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.

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

Purpose: To evaluate plan quality of a novel MRI‐compatible direction modulated brachytherapy (DMBT) tandem applicator using 192Ir, 60Co, and 169Yb 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 192Ir, 60Co, and 169Yb HDR sources in a water phantom against the literature data. 45 clinical cases that were treated using conventional tandem‐and‐ring applicators with 192Ir source (192Ir‐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 192Ir‐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 192Ir‐T&R and DMBT T&R plans with all three sources (P > 0.093). 60Co‐DMBT T&R generated greater hot spots and less dose homogeneity in the target volumes compared with the 192Ir‐ and 169Yb‐DMBT T&R plans. Mean OAR doses in the DMBT T&R plans were significantly smaller (P < 0.0084) than the 192Ir‐T&R plans. Mean bladder D2 cm3 was reduced by 4.07%, 4.15%, and 5.13%, for the 192Ir‐, 60Co‐, and 169Yb‐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 192Ir‐, 60Co‐, and 169Yb‐DMBT T&R plans respectively. The DMBT T&R plans with the 169Yb 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 169Yb‐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.

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.

SU-F-T-30: Comprehensive Dosimetric Characterization of the Novel Direction Modulation Brachytherapy (DMBT) Tandem Applicator Using Monte Carlo Simulations

PURPOSE To characterize the dosimetric properties/distributions of the novel proposed direction modulated brachytherapy (DMBT) tandem applicator in combination with 192Ir HDR source, and compare against conventional tandem design, using Monte Carlo simulations. METHODS The proposed DMBT tandem applicator is designed for image-guided adaptive brachytherapy, especially MRI, of cervical cancer. It has 6 peripheral holes of 1.3-mm width, grooved along a 5.4-mm diameter nonmagnetic tungsten alloy rod of density 18.0 g/cc, capable of generating directional dose profiles - leading to enhanced dose sculpting capacity through inverse planning. In-water dosimetric parameters for the DMBT and conventional tandems have been calculated for various radial distances away and around the tandems. For the DMBT tandem, the cumulative dose from the 192Ir source occupying 1) one and 2) all six holes in equal dwell times was calculated and normalized to match the dose rate of the open source (in conventional tandem) at 1 cm from the center. This is done to compare and contrast the characteristic dose distributions to that of the isotropic TG43-based 192Ir source. RESULTS All dose rates were normalized at 1-cm radius from the center of the applicators, containing source(s). The normalized dose rates at 0.5, 3.0, and 5.0-cm radiuses were then 388, 11.3, and 4.1% for conventional tandem, 657, 8.1, and 2.7% for DMBT tandem with the source in one hole at front entrance, and 436, 10.9, and 3.8% for DMBT tandem with the source in all six holes. For the DMBT tandem case with the source in one hole, the backside transmissions were 47, 2.4, and 0.9%, respectively. CONCLUSION The DMBT tandem is able to generate closely similar dosimetric characteristics as that of the single-channel conventional tandem if needed (with the source occupying all six holes), at the same time, generate directional radiation profile(s) for favorably enabling 3D dose sculpting capability.