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: 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.

Purpose: To evaluate the feasibility of a combined PET‐Linac system for real‐time guidance of radiation therapy for tumors that move due to respiration. Method and Materials: We are developing a treatment system that will simultaneously deliver radiation during PET acquisition. A method to compensate for respiratory motion will be to deliver radiation beam‐lets along individual PET lines‐of‐response (LOR's) as they are detected. The system involves rotating a radiation source and PET detectors on a gantry while dynamically controlling a binary multi‐leaf collimator to deliver the beam‐let responses in a 2D helical mode. Simulations were conducted using GATE to model 300 seconds of PET list‐mode acquisition of a ‘hot’ 3 cm diameter tumor exhibiting 3.7 second periodic 2 cm peak‐to‐peak motion in a ‘warm’ background. A 5 cm planning target volume (PTV) was used as a filter to reject LOR's that did not intersect this volume. LOR's that intersected the PTV and whose timestamps were within a 500 ms cutoff window were responded to. A voxel‐based Monte Carlo simulation package was used to model the resultant dose distributions comparing the emission guided (EGRT) method with uniform coverage of the PTV. Results: Composite dose volume histograms were calculated using 10 phases of the motion cycle. Dose to the non‐tumor volume was normalized to the same mean value for both scenarios. The EGRT approach exhibited a non‐uniform dose distribution to the tumor compared to uniform PTV coverage. However, even with the non‐uniformity, there was a 30% relative increase in minimum dose to the tumor volume for the EGRT approach. Conclusion: Although non‐uniform dose delivery to the tumor volume needs to be addressed, the feasibility of using PET to guide radiation delivery in real‐time has been demonstrated.Conflict of Interest: SRM and ASN are co‐founders of a company commercializing emission guided radiation therapy.

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Purpose: Accurate tumor tracking, especially for lung cancer, remains a challenge ineffectively addressed. Many strategies including respiratory gating and fiducial implanting alleviate the problem to different extents however they are sub‐optimal due to indirect tracking. To track the tumor itself, the concept of Emission Guided Radiation therapy(EGRT) was recently proposed. This work serves to demonstrate the feasibility of the EGRT concept within the context of lung cancer treatment. Methods: EGRT is based on the physics principle that lines of response(LOR's) from positron emission events can define the lines of radiation projection passing through the emission sites. It enlightens the design of a radiation delivery system consisting of a linac and PET detectors on a fast rotating closed‐ring gantry. When treating radiotracer administrated patients, PET detectors collect LOR's from tumor uptake sites and the linac responds simultaneously with beamlets of radiation along the same LOR paths. Accurate direct tumor tracking can automatically be achieved with real‐time responses. To validate the EGRT concept, a treatment scheme is designed and implemented for the 4D XCAT phantom with a lung tumor. A conventional treatment is modeled for comparison. Attenuation correction is also implemented in EGRT. The emission process is simulated by Geant4 Application for Tomographic Emission package(GATE) and linac dose delivery is simulated using a voxel‐based Monte Carlo algorithm(VMC++). Results: EGRT, with or without attenuation correction, achieves over 25% and 40% relative dose increase to 100% and 50% of the tumor volume respectively compared to the conventional treatment with all cases normalized to have the same integral dose to lung. Attenuation correction helps achieve a better dose performance. Dose‐peaking in the tumor volume is observed in EGRT, demonstrating automatic tumor tracking. Conclusions: As a new radiation therapy modality with inherent tumor tracking, EGRT has the potential to substantially improve radiation therapy for lung cancer. This study was funded by RefleXion Medical, a company commercializing PET‐guided radiotherapy. SRM, ASN and LZ have financial interest in RefleXion.