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The therapeutic landscape of metastatic prostate cancer has undergone a profound revolution in recent years. In addition to the introduction of novel molecules in the clinics, the field has witnessed a tremendous development of functional imaging modalities adding new biological insights which can ultimately inform tailored treatment strategies, including local therapies. The evolution and rise of Stereotactic Body Radiotherapy (SBRT) have been particularly notable in patients with oligometastatic disease, where it has been demonstrated to be a safe and effective treatment strategy yielding favorable results in terms of disease control and improved oncological outcomes. The possibility of debulking all sites of disease, matched with the ambition of potentially extending this treatment paradigm to polymetastatic patients in the not-too-distant future, makes Biology-guided Radiotherapy (BgRT) an attractive paradigm which can be used in conjunction with systemic therapy in the management of patients with metastatic prostate cancer. [ABSTRACT FROM AUTHOR]

Background: 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. Purpose: 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. Methods: 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%). Results: 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%. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: 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. Purpose: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

The therapeutic landscape of metastatic prostate cancer has undergone a profound revolution in recent years. In addition to the introduction of novel molecules in the clinics, the field has witnessed a tremendous development of functional imaging modalities adding new biological insights which can ultimately inform tailored treatment strategies, including local therapies. The evolution and rise of Stereotactic Body Radiotherapy (SBRT) have been particularly notable in patients with oligometastatic disease, where it has been demonstrated to be a safe and effective treatment strategy yielding favorable results in terms of disease control and improved oncological outcomes. The possibility of debulking all sites of disease, matched with the ambition of potentially extending this treatment paradigm to polymetastatic patients in the not-too-distant future, makes Biology-guided Radiotherapy (BgRT) an attractive paradigm which can be used in conjunction with systemic therapy in the management of patients with metastatic prostate cancer.

We aimed to compare prototype treatment plans for a new biology-guided radiotherapy (BgRT) machine in its intensity-modulated radiation therapy (IMRT) mode with those using existing IMRT delivery techniques in treatment of nasopharyngeal carcinoma (NPC). We retrospectively selected ten previous NPC patients treated in 33 fractions according to the NRG-HN001 treatment protocol. Three treatment plans were generated for each patient: a helical tomotherapy (HT) plan with a 2.5-cm jaw, a volumetric modulated arc therapy (VMAT) plan using 2 to 4 6-MV arc fields, and a prototype IMRT plan for a new BgRT system which uses a 6-MV photon beam on a ring gantry that rotates at 60 rotations per minute with a couch that moves in small incremental steps. Treatment plans were compared using dosimetric parameters to planning target volumes (PTVs) and organs at risk (OARs) as specified by the NRG-HN001 protocol. Plans for the three modalities had comparable dose coverage, mean dose, and dose heterogeneity to the primary PTV, while the prototype IMRT plans had greater dose heterogeneity to the non-primary PTVs, with the average homogeneity index ranging from 1.28 to 1.50 in the prototype plans. Six of all the 7 OAR mean dose parameters were lower with statistical significance in the prototype plans compared to the HT and VMAT plans with the other mean dose parameter being comparable, and all the 18 OAR maximum dose parameters were comparable or lower with statistical significance in the prototype plans. The average left and right parotid mean doses in the prototype plans were 10.5 Gy and 10.4 Gy lower than those in the HT plans, respectively, and were 5.1 Gy and 5.2 Gy lower than those in the VMAT plans, respectively. Compared to that with the HT and VMAT plans, the treatment time was longer with statistical significance with the prototype IMRT plans. Based on dosimetric comparison of ten NPC cases, the prototype IMRT plans achieved comparable or better critical organ sparing compared to the HT and VMAT plans for definitive NPC radiotherapy. However, there was higher dose heterogeneity to non-primary targets and longer estimated treatment time with the prototype plans. [ABSTRACT FROM AUTHOR]

Biology-guided radiation therapy is an emerging field whereby delivery of external beam radiotherapy incorporates biological/molecular imaging to inform radiation treatment. At present, there is evidence for the use of functional imaging such as PET to evaluate treatment response in patients both during and after radiation treatment as well as to provide a method of adapting or selecting patient-specific treatments. Examples in thoracic, gastrointestinal, and hematologic malignancies are provided. Improvements in PET metrics, thresholds, and novel radiotracers will further move this novel field forward., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Biology-guided radiotherapy (BgRT) is a novel technique of external beam radiotherapy, combining positron emission tomography-computed tomography (PET-CT) with a linear accelerator (LINAC). The key innovation is to utilize PET signals from tracers in tumor tissues for real-time tracking and guiding beamlets. Compared with a traditional LINAC system, a BgRT system is more complex in hardware design, software algorithm, system integration and clinical workflow. RefleXion Medical has developed the world's first BgRT system. Nevertheless, its actively advertised function, PET-guided radiotherapy, is still in the research and development phase. In this review study, we presented a number of issues related to BgRT, including its technical advantages and potential challenges.