Clinical Feasibility Study of Gold Nanoparticles as Theragnostic Agents for Precision Radiotherapy.

BACKGROUND: Gold nanoparticles (AuNP) may be useful in precision radiotherapy and disease monitoring as theragnostic agents. In diagnostics, they can be detected by computerized tomography (CT) because of their higher atomic number. AuNP may also improve the treatment results in radiotherapy due to a higher cross-section, locally improving the physically absorbed dose. METHODS: Key parameters values involved in the use of AuNP were imposed to be optimal in the clinical scenario. Mass concentration of AuNP as an efficient contrast agent in clinical CT was found and implemented in a Monte Carlo simulation method for dose calculation under different proposed therapeutic beams. The radiosensitization effect was determined in irradiated cells with AuNP. RESULTS: an AuNP concentration was found for a proper contrast level and enhanced therapeutic effect under a beam typically used for image-guided therapy and monitoring. This lower energetic proposed beam showed potential use for treatment monitoring in addition to absorbed dose enhancement and higher radiosensitization at the cellular level. CONCLUSION: the results obtained show the use of AuNP concentration around 20 mg Au·mL-1 as an efficient tool for diagnosis, treatment planning, and monitoring treatment. Simultaneously, the delivered prescription dose provides a higher radiobiological effect on the cancer cell for achieving precision radiotherapy.

Implications of the Harmonization of [18F]FDG-PET/CT Imaging for Response Assessment of Treatment in Radiotherapy Planning.

The purpose of this work is to present useful recommendations for the use of [18F]FDG-PET/CT imaging in radiotherapy planning and monitoring under different versions of EARL accreditation for harmonization of PET devices. A proof-of-concept experiment designed on an anthropomorphic phantom was carried out to establish the most suitable interpolation methods of the PET images in the different steps of the planning procedure. Based on PET/CT images obtained by using these optimal interpolations for the old EARL accreditation (EARL1) and for the new one (EARL2), the treatment plannings of representative actual clinical cases were calculated, and the clinical implications of the resulting differences were analyzed. As expected, EARL2 provided smaller volumes with higher resolution than EARL1. The increase in the size of the reconstructed volumes with EARL1 accreditation caused high doses in the organs at risk and in the regions adjacent to the target volumes. EARL2 accreditation allowed an improvement in the accuracy of the PET imaging precision, allowing more personalized radiotherapy. This work provides recommendations for those centers that intend to benefit from the new accreditation, EARL2, and can help build confidence of those that must continue working under the EARL1 accreditation.

Accurate, robust and harmonized implementation of morpho-functional imaging in treatment planning for personalized radiotherapy.

In this work we present a methodology able to use harmonized PET/CT imaging in dose painting by number (DPBN) approach by means of a robust and accurate treatment planning system. Image processing and treatment planning were performed by using a Matlab-based platform, called CARMEN, in which a full Monte Carlo simulation is included. Linear programming formulation was developed for a voxel-by-voxel robust optimization and a specific direct aperture optimization was designed for an efficient adaptive radiotherapy implementation. DPBN approach with our methodology was tested to reduce the uncertainties associated with both, the absolute value and the relative value of the information in the functional image. For the same H&N case, a single robust treatment was planned for dose prescription maps corresponding to standardized uptake value distributions from two different image reconstruction protocols: One to fulfill EARL accreditation for harmonization of [18F]FDG PET/CT image, and the other one to use the highest available spatial resolution. Also, a robust treatment was planned to fulfill dose prescription maps corresponding to both approaches, the dose painting by contour based on volumes and our voxel-by-voxel DPBN. Adaptive planning was also carried out to check the suitability of our proposal. Different plans showed robustness to cover a range of scenarios for implementation of harmonizing strategies by using the highest available resolution. Also, robustness associated to discretization level of dose prescription according to the use of contours or numbers was achieved. All plans showed excellent quality index histogram and quality factors below 2%. Efficient solution for adaptive radiotherapy based directly on changes in functional image was obtained. We proved that by using voxel-by-voxel DPBN approach it is possible to overcome typical drawbacks linked to PET/CT images, providing to the clinical specialist confidence enough for routinely implementation of functional imaging for personalized radiotherapy.

Clinical implementation of combined modulated electron and photon beams with conventional MLC for accelerated partial breast irradiation.

PURPOSE: To report the clinical implementation of a novel external beam radiotherapy technique for accelerated partial breast irradiation treatments based on combined electron and photon modulated beams radiotherapy (MERT+IMRT) with conventional MLC. MATERIALS AND METHODS: A group of patients was selected to test the viability of the technique. The prescribed dose was 38.5Gy, following a hypofractionated schema, and the structures were defined following the NSABP-B39/RTOG-0413 protocol. The plans were calculated with an in-house Monte Carlo based planning system to consider explicitly the particle interactions with the MLC. An ad-hoc breast phantom was designed for a specific QA protocol. A reduced SSD was used for electron beams. Toxicity and cosmetic effects were assessed at every follow-up visit. RESULTS: All the plans achieved the dosimetric objectives and fulfilled the specific quality assurance protocol. Treatment delivery did not entail additional drawbacks for the clinical routine. Moderate or severe grade of toxicity was not reported, and the cosmetic results were comparable to those obtained with other APBI techniques. CONCLUSIONS: Results showed that MERT+IMRT with the MLC is a feasible and secure technique, and easy to be extended to other centers with the implementation of the adequate software for planning.