By providing effective shading correction, our approach has the potential to improve the accuracy of more advanced CBCT-based clinical applications for IGRT, such as tumor delineation and dose calculation.

As a new radiation therapy modality with inherent tumor tracking, EGRT has the potential to substantially improve targeting in radiation therapy in the presence of intrafractional and interfractional motion.

Purpose/objectives: To provide an order of magnitude estimate of the minimum dose rate (R min ) required by pulsed ultra-high dose rate radiotherapy (FLASH RT) using dimensional analysis. Materials/methods: In this study, we postulate that radiation-induced transient hypoxia inside normal tissue cells during FLASH RT results in better normal tissue sparing over conventional dose rate radiotherapy. We divide the process of cell irradiation by an ultra-short radiation pulse into three sequential phases: (a) The radiation pulse interacts with the normal tissue cells and produces radiation-induced species. (b) The radiation-induced species react with oxygen molecules and reduce the cell environmental oxygen concentration ( O 2 ½ ). (c) Oxygen molecules, from nearest capillaries, diffuse slowly back into the resulted low O 2 ½ regions. By balancing the radiation-induced oxygen depletion in phase II and diffusion-resulted O 2 ½ replenishment in phase III, we can estimate the maximum allowed pulse repetition interval to produce a pulse-to-pulse superimposed O 2 ½ reduction against the baseline O 2½ . If we impose a threshold in radiosensitivity reduction to achieve clinically observable radiotherapy oxygen effect and combine the processes mentioned above, we could estimate the R min required for pulsed FLASH RT through dimensional analysis. Results: The estimated R min required for pulsed FLASH RT is proportional to the product of the oxygen diffusion coefficient and O 2 ½ inside the cell, and inversely proportional to the product of the square of the oxygen diffusion distance and the drop of intracellular O 2 ½ per unit radiation dose. Under typical conditions, our estimation matches the order of magnitude with the dose rates observed in the recent FLASH RT experiments. Conclusions: The R min introduced in this paper can be useful when designing a FLASH RT system. Additionally, our analysis of the chemical and physical processes may provide some insights into the FLASH RT mechanism.

Purpose: Emission guided radiation therapy (EGRT) is a new modality that uses PET emissions in real-time for direct tumor tracking during radiation delivery. Radiation beamlets are delivered along positron emission tomography (PET) lines of response (LORs) by a fast rotating ring therapy unit consisting of a linear accelerator (Linac) and PET detectors. The feasibility of tumor tracking and a primitive modulation method to compensate for attenuation have been demonstrated using a 4D digital phantom in our prior work. However, the essential capability of achieving dose modulation as in conventional intensity modulated radiation therapy (IMRT) treatments remains absent. In this work, the authors develop a planning scheme for EGRT to accomplish sophisticated intensity modulation based on an IMRT plan while preserving tumor tracking. Methods:The planning scheme utilizes a precomputed LOR response probability distribution to achieve desired IMRT planning modulation with effects of inhomogeneous attenuation and nonuniform background activity distribution accounted for. Evaluation studies are performed on a 4D digital patient with a simulated lung tumor and a clinical patient who has a moving breast cancer metastasis in the lung. The Linac dose delivery is simulated using a voxel-based Monte Carlo algorithm. The IMRT plan is optimized for a planning target volume (PTV) that encompasses the tumor motion using the MOSEK package and a Pinnacle 3TM workstation (Philips Healthcare, Fitchburg, WI) for digital and clinical patients, respectively. To obtain the emission data for both patients, the Geant4 application for tomographic emission (GATE) package and a commercial PET scanner are used. As a comparison, 3D and helical IMRT treatments covering the same PTV based on the same IMRT plan are simulated. Results: 3D and helical IMRT treatments show similar dose distribution. In the digital patient case, compared with the 3D IMRT treatment, EGRT achieves a 15.1% relative increase in dose to 95% of the gross tumor volume (GTV) and a 31.8% increase to 50% of the GTV. In the patient case, EGRT yields a 15.2% relative increase in dose to 95% of the GTV and a 20.7% increase to 50% of the GTV. The organs at risk (OARs) doses are kept similar or lower for EGRT in both cases. Tumor tracking is observed in the presence of planning modulation in all EGRT treatments. Conclusions: As compared to conventional IMRT treatments, the proposed EGRT planning scheme allows an escalated target dose while keeping dose to the OARs within the same planning limits. With the capabilities of incorporating planning modulation and accurate tumor tracking, EGRT has the potential to greatly improve targeting in radiation therapy and enable a practical and effective implementation of 4D radiation therapy for planning and delivery.