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This position paper, led by the NRG Oncology Particle Therapy Work Group, focuses on the concept of relative biologic effect (RBE) in clinical proton therapy (PT), with the goal of providing recommendations for the next-generation clinical trials with PT on the best practice of investigating and using RBE, which could deviate from the current standard proton RBE value of 1.1 relative to photons. In part 1, current clinical utilization and practice are reviewed, giving the context and history of RBE. Evidence for variation in RBE is presented along with the concept of linear energy transfer (LET). The intertwined nature of tumor radiobiology, normal tissue constraints, and treatment planning with LET and RBE considerations is then reviewed. Part 2 summarizes current and past clinical data and then suggests the next steps to explore and employ tools for improved dynamic models for RBE. In part 3, approaches and methods for the next generation of prospective clinical trials are explored, with the goal of optimizing RBE to be both more reflective of clinical reality and also deployable in trials to allow clinical validation and interpatient comparisons. These concepts provide the foundation for personalized biologic treatments reviewed in part 4. Finally, we conclude with a summary including short- and long-term scientific focus points for clinical PT. The practicalities and capacity to use RBE in treatment planning are reviewed and considered with more biological data in hand. The intermediate step of LET optimization is summarized and proposed as a potential bridge to the ultimate goal of case-specific RBE planning that can be achieved as a hypothesis-generating tool in near-term proton trials. [ABSTRACT FROM AUTHOR]

The past decade has seen a dramatic increase in interest in the use of gold nanoparticles (GNPs) as radiation sensitizers for radiation therapy. This interest was initially driven by their strong absorption of ionizing radiation and the resulting ability to increase dose deposited within target volumes even at relatively low concentrations. These early observations are supported by extensive experimental validation, showing GNPs' efficacy at sensitizing tumors in both in vitro and in vivo systems to a range of types of ionizing radiation, including kilovoltage and megavoltage X rays as well as charged particles. Despite this experimental validation, there has been limited translation of GNP-mediated radiation sensitization to a clinical setting. One of the key challenges in this area is the wide range of experimental systems that have been investigated, spanning a range of particle sizes, shapes, and preparations. As a result, mechanisms of uptake and radiation sensitization have remained difficult to clearly identify. This has proven a significant impediment to the identification of optimal GNP formulations which strike a balance among their radiation sensitizing properties, their specificity to the tumors, their biocompatibility, and their imageability in vivo. This white paper reviews the current state of knowledge in each of the areas concerning the use of GNPs as radiosensitizers, and outlines the steps which will be required to advance GNP-enhanced radiation therapy from their current pre-clinical setting to clinical trials and eventual routine usage. [ABSTRACT FROM AUTHOR]

Requirements for the use of fiducials vary across different modalities. For the frameless robotic radiosurgery system treatments, a standard fiducial with a minimum diameter of 0.75 mm is essential, whereas for proton therapy, a maximum fiducial diameter of 0.50 mm is allowed. Larger fiducials pose challenges for proton treatments due to excessive material within the beam path, resulting in clinically unacceptable beam perturbations. This necessitates accurate knowledge of the treatment modality at the time of fiducial insertion, leading to operational complications since such treatment plans might not be available at simulation time. Our study aimed to investigate the feasibility of modulating fiducial parameters to preserve trackability while minimizing proton beam perturbation, thereby enabling the use of a single fiducial across all modalities. Custom-made fiducials with a diameter of 0.75 mm and varying pitch values, resulting in lower amounts of material within the fiducial structure, were fabricated (Table 1). The trackability of these fiducials was evaluated using the frameless robotic radiosurgery system. Furthermore, a phantom containing both standard and customized fiducials was positioned under a proton beam, with radiographic films placed at various depths to capture and quantify beam perturbation. Trackability of fiducials seemed to be independent of the pitch value. The customized fiducials, all with diameter of 0.75 mm, demonstrated a notable reduction in proton beam perturbation. Particularly, at greater depths, such as 1.2 cm, they exhibited lower levels of perturbation compared to a standard fiducial with diameter of 0.5 mm, (Table 1). Fiducials can be optimized to ensure compatibility across various radiation treatment modalities. An ideal fiducial would possess a larger diameter for enhanced trackability while incorporating less materials, achieved through higher pitch values, to minimize beam perturbation. Further clinical investigation is warranted to assess the mobility and performance of customized fiducials within patient anatomy. [ABSTRACT FROM AUTHOR]