A dose-volume constraint (DVC) projection-based algorithm for IMPT inverse planning optimization.

PURPOSE: Provide a projection-based algorithm to solve the class of optimization problems encountered in intensity modulated proton therapy (IMPT). The algorithm can handle percentage dose-volume constraints (DVCs) that are usually found in such problems. METHODS: To seek a feasible solution, the automatic relaxation method was used to project the spot weight vector onto the interval defined by lower and upper bound target dose constraints. The obtained solution was optimized separately based on the objective of each organ at risk (OAR) in addition to maximizing the minimum target dose using the bisection search method using a stopping criterion of 10 cGy. The combined weight was used in the CQ algorithm to solve the split feasibility problem but with a special projection technique due to the nonconvexity of DVCs. The algorithm was applied to four clinical IMPT cases (meningioma, prostate, tongue, and oropharynx) and compared to the corresponding treatment plans optimized in Eclipse. RESULTS: The treatment plans obtained, for the four cases, using the BCQ-ARM algorithm have dosimetric endpoints that are similar to their counterparts generated from Eclipse. The algorithm worked equally well with all cases, including the complex head and neck ones. The stopping criterion of 10 cGy results in making the generated plans slightly less optimal ( ε $\epsilon$ -optimal) rather than optimal, but with the advantage of the possibility of generating a database of plans. CONCLUSIONS: The application of the BCQ-ARM algorithm to different cases of IMPT plans with DVCs was demonstrated. The algorithm is successful in generating plans that are dosimetrically equivalent to their corresponding Eclipse plans. Thus, it is suitable to generate optimized treatment plans in a clinically reasonable time frame.

Affordable compensator for IMRT delivery designed for low-and-middle income countries, a Monte Carlo study.

We propose a novel cost-effective compensator that can be used to facilitate access to IMRT in low-and-middle income countries. The compensator has the advantages of simplicity, less downtime, increased reliability and less impact on treatment quality from patient motion during treatment. Moreover, the system can be used with either a cobalt-60 unit or linear accelerator. In this Monte Carlo study, the dosimetric properties of the new compensator design have been evaluated. Results were obtained for different field sizes of cobalt teletherapy machine, and the dose was scored at 0.5 cm depth in a water phantom. The effects of compensator thickness, filling material type and shape, and field size were identified. Furthermore, the percentage depth dose and beam profiles for various field sizes and at different depths were obtained. Beam profiles show no significant signature of the beads relative to a solid compensator; in addition, they exhibit a better flatness while preserving symmetry for all field sizes. A reusable bead-based compensator appears to be feasible, and provides dose distribution similar to a solid compensator with low cost and no hazards. Our results avail the ongoing efforts to expand the reach to IMRT in low- and middle-income countries.

Impact of the MLC leaf-tip model in a commercial TPS: Dose calculation limitations and IROC-H phantom failures.

PURPOSE: Treatment planning system (TPS) dose calculation is sensitive to multileaf collimator (MLC) modeling, especially when treating with intensity-modulated radiation therapy (IMRT) or VMAT. This study investigates the dosimetric impact of the MLC leaf-tip model in a commercial TPS (RayStation v.6.1). The detectability of modeling errors was assessed through both measurements with an anthropomorphic head-and-neck phantom and patient-specific IMRT QA using a 3D diode array. METHODS AND MATERIALS: An Agility MLC (Elekta Inc.) was commissioned in RayStation. Nine IMRT and VMAT plans were optimized to treat the head-and-neck phantom from the Imaging and Radiation Oncology Core Houston branch (IROC-H). Dose distributions for each plan were re-calculated on 27 beam models, varying leaf-tip width (2.0, 4.5, and 6.5 mm) and leaf-tip offset (-2.0 to +2.0 mm) values. Doses were compared to phantom TLD measurements. Patient-specific IMRT QA was performed, and receiver-operating characteristic (ROC) analysis was performed to determine the detectability of modeling errors. RESULTS: Dose calculations were very sensitive to leaf-tip offset values. Offsets of ±1.0 mm resulted in dose differences up to 10% and 15% in the PTV and spinal cord TLDs respectively. Offsets of ±2.0 mm caused dose deviations up to 50% in the spinal cord TLD. Patient-specific IMRT QA could not reliably detect these deviations, with an ROC area under the curve (AUC) value of 0.537 for a ±1.0 mm change in leaf-tip offset, corresponding to >7% dose deviation. Leaf-tip width had a modest dosimetric impact with <2% and 5.6% differences in the PTV and spinal cord TLDs respectively. CONCLUSIONS: Small changes in the MLC leaf-tip offset in this TPS model can cause large changes in the calculated dose for IMRT and VMAT plans that are difficult to identify through either dose curves or standard patient-specific IMRT QA. These results may, in part, explain the reported high failure rate of IROC-H phantom tests.

Enhancement of linear energy transfer in gold nanoparticles mediated radiation therapy.

OBJECTIVE: The metric dose enhancement ratio (DER) has been widely used to assess the enhancing capability of gold nanoparticles (GNPs). However, there is a large disparity between the observed radiobiological outcome and DER values. A new metric, linear energy transfer enhancement ratio (LETER), is introduced to bridge the gap between theoretical predictions and the experimentally measured sensitization. METHODS: The radiation transport code SCEPTRE is used to examine the efficacy of the proposed new metric. Different clusters of GNPs irradiated with x-ray photons generated at 120 kVp and therapeutic 6 MV photon beams are investigated. For each pattern, two GNPs sizes are examined 50 and 100 nm. RESULTS: An enhancement in the linear energy transfer has been observed for both energies. In the case of 120 kVp, LETER is substantially lower than DER; moreover, it decreases with increasing GNP size. On the other hand, the results of 6 MV show that LETER is relatively higher than DER, and it increases with the size of GNP. For the studied energies, LETER is in good agreement with the sensitization reported in the literature. CONCLUSION: The results indicate the merit of LETER as a better indicator of the radiobiological outcome of GNP aided radiotherapy.

Radio-sensitization efficacy of gold nanoparticles in inhalational nanomedicine and the adverse effect of nano-detachment due to coating inactivation.

Gold nanoparticles (GNPs) are an emerging area of interest in radiation therapy due to their unique radio-sensitizing properties. In the literature, the enhancing capability of GNPs is usually quantified using the metric dose enhancement ratio (DER). Traditionally, the focus of the vast majority of studies has always been on intravenous administration of GNPs. However, recent work showed the potential of using GNP inhalation, rather than intravenous injection, to enhance the dose to the lung. Yet, some of these studies are employing simplistic analytical methods to calculate DER and, thus far, there are no detailed computations of the enhancement profiles therein. Moreover, the coating on the GNP surface can be adversely affected by the large gradient of the radiation dose in the immediate vicinity of GNPs, leading to the rupture of ligands and detachment of GNPs from the surface of the membrane, and hence the loss of its efficacy. In this study, a next-generation deterministic code was used to resolve the DER profile at the interface between the septum, air, and surface of GNPs when they are attached and detached. The results show that the large values of DER in conjunction with the developed hot spots are very effective in lung treatment; on the other hand, coating rupture can lead to significant reduction in DER that may reach 64%. Thus, GNPs can be beneficial in inhalational medicine to treat lung cancer, provided that more comprehensive studies on the characteristics of the coating are addressed to maximize the radio-therapeutic benefit of GNPs.

Minimizing the potential of cancer recurrence and metastasis by the use of graphene oxide nano-flakes released from smart fiducials during image-guided radiation therapy.

An increasing number of studies show that cancer stem cells become more invasive and may escape into blood stream and lymph nodes before they have received a lethal dose during radiation therapy. Recently, it has been found that graphene oxide (GO) can selectively inhibit the proliferative expansion of cancer stem cells across multiple tumor types. In this study, we investigate the feasibility of using GO during radiotherapy to synergistically inhibit cancer stem cells, and lower the risk of cancer metastasis and recurrence. We hypothesize that graphene oxide nano-flakes (GONFs) released from newly-designed radiotherapy biomaterials (fiducial) can reach targeted tumor cells within 14-21 days. These are the typical time periods between the implantation of the fiducial and the start of image-guided radiation therapy. To test this hypothesis, the spatial-temporal diffusion of GONFs in soft tissue is investigated as a function of different particle sizes. Toxicity of GONFs to normal (HUVEC) and cancer (A549) cells has been assessed using the MTT assay. In addition, the survival fraction of A549 cells treated with GONFs is determined via clonogenic assay during radiotherapy. The diffusion study shows that only GONFs sizes of 50 and 200 nm could achieve the desired concentration of 50 µg/mL for 2 cm diameter tumor after 14 and 21 days respectively. The clonogenic and the MTT assay confirm the additional benefit of GONFs in killing lung cancer cells during radiotherapy. This work avails ongoing in vivo studies that use GONFs to enhance the treatment outcome for cancer patients during radiation therapy.

A ring-based compensator IMRT system optimized for low- and middle-income countries: Design and treatment planning study.

PURPOSE: We propose a novel compensator-based IMRT system designed to provide a simple, reliable, and cost-effective adjunct technology, with the goal of expanding global access to advanced radiotherapy techniques. The system would employ easily reusable tungsten bead compensators that operate independent of a gantry (e.g., mounted in a ring around the patient). Thereby the system can be retrofitted to existing linac and cobalt teletherapy units. This study explores the quality of treatment plans from the proposed system and the dependence on associated design parameters. METHODS: We considered 60 Co-based plans as the most challenging scenario for dosimetry and benchmarked them against clinical MLC-based plans delivered on a linac. Treatment planning was performed in the Pinnacle treatment planning system with commissioning based on Monte Carlo simulations of compensated beams. 60 Co-compensator IMRT plans were generated for five patients with head-and-neck cancer and five with gynecological cancer and compared to respective IMRT plans using a 6 MV linac beam with an MLC. The dependence of dosimetric endpoints on compensator resolution, thickness, position, and number of beams was assessed. Dosimetric accuracy was validated by Monte Carlo simulations of dose distribution in a water phantom from beams with the IMRT plan compensators. RESULTS: The 60 Co-compensator plans had on average equivalent PTV coverage and somewhat inferior OAR sparing compared to the 6 MV-MLC plans, but the differences in dosimetric endpoints were clinically acceptable. Calculated treatment times for head-and-neck plans were 7.6 ± 2.0 min vs 3.9 ± 0.8 min (6 MV-MLC vs 60 Co-compensator) and for gynecological plans were 8.7 ± 3.1 min vs 4.3 ± 0.4 min. Plan quality was insensitive to most design parameters over much of the ranges studied, with no degradation found when the compensator resolution was finer than 6 mm, maximum thickness at least 2 tenth-value-layers, and more than five beams were used. Source-to-compensator distances of 53 and 63 cm resulted in very similar plan quality. Monte Carlo simulations suggest no increase in surface dose for the geometries considered here. Simulated dosimetric validation tests had median gamma pass rates of 97.6% for criteria of 3% (global)/3 mm with a 10% threshold. CONCLUSIONS: The novel ring-compensator IMRT system can produce plans of comparable quality to standard 6 MV-MLC systems. Even when 60 Co beams are used the plan quality is acceptable and treatment times are substantially reduced. 60 Co-compensator IMRT plans are adequately modeled in an existing commercial treatment planning system. These results motivate further development of this low-cost adaptable technology with translation through clinical trials and deployment to expand the reach of IMRT in low- and middle-income countries.

Angular dose anisotropy around gold nanoparticles exposed to X-rays.

Gold nanoparticle (GNP) radiotherapy has recently emerged as a promising modality in cancer treatment. The use of high atomic number nanoparticles can lead to enhanced radiation dose in tumors due to low-energy leakage electrons depositing in the vicinity of the GNP. A single metric, the dose enhancement ratio has been used in the literature, often in substantial disagreement, to quantify the GNP's capacity to increase local energy deposition. This 1D approach neglects known sources of dose anisotropy and assumes that one average value is representative of the dose enhancement. Whether this assumption is correct and within what accuracy limits it could be trusted, have not been studied due to computational difficulties at the nanoscale. Using a next-generation deterministic computational method, we show that significant dose anisotropy exists which may have radiobiological consequences, and can impact the treatment outcome as well as the development of treatment planning computational methods.