Demonstration of real-time positron emission tomography biology-guided radiotherapy delivery to targets.

Biology-guided radiotherapy (BgRT) is a novel technology that uses positron emission tomography (PET) data to direct radiotherapy delivery in real-time. BgRT enables the precise delivery of radiation doses based on the PET signals emanating from PET-avid tumors on the fly. In this way, BgRT uniquely utilizes radiotracer uptake as a biological beacon for controlling and adjusting dose delivery in real-time to account for target motion. To demonstrate using real-time PET for BgRT delivery on the RefleXion X1 radiotherapy machine. The X1 radiotherapy machine is a rotating ring-gantry radiotherapy system that generates a nominal 6MV photon beam, PET, and computed tomography (CT) components. The system utilizes emitted photons from PET-avid targets to deliver effective radiation beamlets or pulses to the tumor in real-time. This study demonstrated a real-time PET BgRT delivery experiment under three scenarios. These scenarios included BgRT delivering to (S1) a static target in a homogeneous and heterogeneous environment, (S2) a static target with a hot avoidance structure and partial PET-avid target, and (S3) a moving target. The first step was to create stereotactic body radiotherapy (SBRT) and BgRT plans (offline PET data supported) using RefleXion's custom-built treatment planning system (TPS). Additionally, to create a BgRT plan using PET-guided delivery, the targets were filled with 18F-Fluorodeoxyglucose (FDG), which represents a tumor/target, that is, PET-avid. The background materials were created in the insert with homogeneous water medium (for S1) and heterogeneous water with styrofoam mesh medium. A heterogeneous background medium simulated soft tissue surrounding the tumor. The treatment plan was then delivered to the experimental setups using a pre-commercial version of the X1 machine. As a final step, the dosimetric accuracy for S1 and S2 was assessed using the ArcCheck analysis tool-the gamma criteria of 3%/3 mm. For S3, the delivery dose was quantified using EBT-XD radiochromic film. The accuracy criteria were based on coverage, where 100% of the clinical target volume (CTV) receives at least 97% of the prescription dose, and the maximum dose in the CTV was ≤130% of the maximum planned dose (97 % ≤ CTV ≤ 130%). For the S1, both SBRT and BgRT deliveries had gamma pass rates greater than 95% (SBRT range: 96.9%-100%, BgRT range: 95.2%-98.9%), while in S2, the gamma pass rate was 98% for SBRT and between 95.2% and 98.9% for BgRT plan delivering. For S3, both SBRT and BgRT motion deliveries met CTV dose coverage requirements, with BgRT plans delivering a very high dose to the target. The CTV dose ranges were (a) SBRT:100.4%-120.4%, and (b) BgRT: 121.3%-139.9%. This phantom-based study demonstrated that PET signals from PET-avid tumors can be utilized to direct real-time dose delivery to the tumor accurately, which is comparable to the dosimetric accuracy of SBRT. Furthermore, BgRT delivered a PET-signal controlled dose to the moving target, equivalent to the dose distribution to the static target. A future study will compare the performance of BgRT with conventional image-guided radiotherapy.

Oderinde OM ，Narayanan M ，Olcott P ，Voronenko Y ，Burns J ，Xu S ，Shao L ，Feghali KAA ，Shirvani SM ，Surucu M ，Kuduvalli G ... -  《-》

Commissioning of a novel PET-Linac for biology-guided radiotherapy (BgRT).

Biology-guided radiotherapy (BgRT) is a novel radiotherapy delivery technique that utilizes the tumor itself to guide dynamic delivery of treatment dose to the tumor. The RefleXion X1 system is the first radiotherapy system developed to deliver SCINTIX® BgRT. The X1 is characterized by its split arc design, employing two 90-degree positron emission tomography (PET) arcs to guide therapeutic radiation beams in real time, currently cleared by FDA to treat bone and lung tumors. This study aims to comprehensively evaluate the capabilities of the SCINTIX radiotherapy delivery system by evaluating its sensitivity to changes in PET contrast, its adaptability in the context of patient motion, and its performance across a spectrum of prescription doses. A series of experimental scenarios, both static and dynamic, were designed to assess the SCINTIX BgRT system's performance, including an end-to-end test. These experiments involved a range of factors, including changes in PET contrast, motion, and prescription doses. Measurements were performed using a custom-made ArcCHECK insert which included a 2.2 cm spherical target and a c-shape structure that can be filled with a PET tracer with varying concentrations. Sinusoidal and cosine4 motion patterns, simulating patient breathing, was used to test the SCINTIX system's ability to deliver BgRT during motion-induced challenges. Each experiment was evaluated against specific metrics, including Activity Concentration (AC), Normalized Target Signal (NTS), and Biology Tracking Zone (BTZ) bounded dose-volume histogram (bDVH) pass rates. The accuracy of the delivered BgRT doses on ArcCHECK and EBT-XD film were evaluated using gamma 3%/2 mm and 3%/3 mm analysis. In static scenarios, the X1 system consistently demonstrated precision and robustness in SCINTIX dose delivery. The end-to-end delivery to the spherical target yielded good results, with AC and NTS values surpassing the critical thresholds of 5 kBq/mL and 2, respectively. Furthermore, bDVH analysis consistently confirmed 100% pass rates. These results were reaffirmed in scenarios involving changes in PET contrast, emphasizing the system's ability to adapt to varying PET avidities. Gamma analysis with 3%/2 mm (10% dose threshold) criteria consistently achieved pass rates > 91.5% for the static tests. In dynamic SCINTIX delivery scenarios, the X1 system exhibited adaptability under conditions of motion. Sinusoidal and cosine4 motion patterns resulted in 3%/3 mm gamma pass rates > 87%. Moreover, the comparison with gated stereotactic body radiotherapy (SBRT) delivery on a conventional c-arm Linac resulted in 93.9% gamma pass rates and used as comparison to evaluate the interplay effect. The 1 cm step shift tests showed low overall gamma pass rates of 60.3% in ArcCHECK measurements, while the doses in the PTV agreed with the plan with 99.9% for 3%/3 mm measured with film. The comprehensive evaluation of the X1 radiotherapy delivery system for SCINTIX BgRT demonstrated good agreement for the static tests. The system consistently achieved critical metrics and delivered the BgRT doses per plan. The motion tests demonstrated its ability to co-localize the dose where the PET signal is and deliver acceptable BgRT dose distributions.

Surucu M ，Ashraf MR ，Romero IO ，Zalavari LT ，Pham D ，Vitzthum LK ，Gensheimer MF ，Yang Y ，Xing L ，Kovalchuk N ，Han B ... -  《-》

The technical design and concept of a PET/CT linac for biology-guided radiotherapy.

This is a summary of the design and concept of the RefleXion X1, a system for biology-guided radiotherapy (BgRT). This system is a multi-modal tomography (PET, fan-beam kVCT, and MVD) treatment machine that utilizes imaging and therapy planes for optimized beam delivery of IMRT, SBRT, SRS, and BgRT radiotherapy regimens. For BgRT delivery specifically, annihilation photons emanating outward from a PET-avid tumor are used to guide the delivery of beamlets of radiation to the tumor at sub-second latency. With the integration of PET detectors, rapid beam-station delivery, real-time tracking, and high-frequency multi-leaf collimation, the BgRT system has the potential to deliver a highly conformal treatment to malignant lesions while minimizing dose to surrounding healthy tissues. Furthermore, the potential use of a single radiotracer injection to guide radiotherapy to multiple targets opens avenues for debulking in advanced and metastatic disease states.

Oderinde OM ，Shirvani SM ，Olcott PD ，Kuduvalli G ，Mazin S ，Larkin D ... -  《Clinical and Translational Radiation Oncology》

Treatment planning system commissioning of the first clinical biology-guided radiotherapy machine.

The RefleXion X1 is a novel radiotherapy machine designed for image-guided radiotherapy (IGRT) and biology-guided radiotherapy (BgRT). Its treatment planning system (TPS) generates IMRT and SBRT plans for a 6MV-FFF beam delivered axially via 50 firing positions with the couch advancing every 2.1 mm. The purpose of this work is to report the TPS commissioning results for the first clinical installation of RefleXion™ X1. CT images of multiple phantoms were imported into the RefleXion TPS to evaluate the accuracy of data transfer, anatomical modeling, plan evaluation, and dose calculation. Comparisons were made between the X1, Eclipse™, and MIM™. Dosimetric parameters for open static fields were evaluated in water and heterogeneous slab phantoms. Representative clinical IMRT and SBRT cases were planned and verified with ion chamber, film, and ArcCHECK@ measurements. The agreement between TPS and measurements for various clinical plans was evaluated using Gamma analysis with a criterion of 3%/2 mm for ArcCHECK@ and film. End-to-end (E2E) testing was performed using anthropomorphic head and lung phantoms. The average difference between the TPS-reported and known HU values was -1.4 ± 6.0 HU. For static fields, the agreements between the TPS-calculated and measured PDD10 , crossline profiles, and inline profiles (FWHM) were within 1.5%, 1.3%, and 0.5 mm, respectively. Measured output factors agreed with the TPS within 1.3%. Measured and calculated dose for static fields in heterogeneous phantoms agreed within 2.5%. The ArcCHECK@ mean absolute Gamma passing rate was 96.4% ± 3.4% for TG 119 and TG 244 plans and 97.8% ± 3.6% for the 21 clinical plans. E2E film analysis showed 0.8 mm total targeting error for isocentric and 1.1 mm for off-axis treatments. The TPS commissioning results of the RefleXion X1 TPS were within the tolerances specified by AAPM TG 53, MPPG 5.a, TG 119, and TG 148. A subset of the commissioning tests has been identified as baseline data for an ongoing QA program.

Simiele E ，Capaldi D ，Breitkreutz D ，Han B ，Yeung T ，White J ，Zaks D ，Owens M ，Maganti S ，Xing L ，Surucu M ，Kovalchuk N ... -  《Journal of Applied Clinical Medical Physics》

Feasibility of Biology-guided Radiotherapy (BgRT) Targeting Fluorodeoxyglucose (FDG) avid liver metastases.

Chau B ，Abuali T ，Shirvani SM ，Leung D ，Al Feghali KA ，Hui S ，McGee H ，Han C ，Liu A ，Amini A ... -  《Radiation Oncology》