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A Biology-guided Radiotherapy (BgRT) based device is designed to use Positron Emission Tomography (PET) signals to achieve tracked dose delivery. The goal of this study is to investigate the dose delivery accuracy in case of interruption during BgRT treatment, and resumption in a separate treatment session for a multi-target delivery, as the PET activity continues to decay. A custom-built large anthropomorphic phantom (LAP) including a 26 mm spherical target with 3D independent motion and two 22 mm spherical targets with 1D sinusoidal motion embedded in water was used. All three targets were filled with FGD in an 8:1 target to background uptake ratio (41.52 kBq/ml in target and 5.19 kBq/ml in background). During BgRT delivery, the treatment was intentionally paused during delivery to the second target and the current treatment session was ended to generate a partial fraction. Then the partial fraction was continued in a new session, where the CT scan localization and PET pre-scan were repeated using the existing PET activity present in the phantom. The newly acquired PET pre-scan, was then used to determine if sufficient PET counts were present to resume treatment delivery. The interruption and recovery algorithm is designed to calculate the fluence that needs to be delivered to the remaining targets as well as the residual fluence to be given to the targets that have already received partial dose prior to the interruption. Once the new fluence is recomputed, the treatment is resumed. The delivered doses were captured using radiochromic film (EBT-XD) inserted in the target as well as post-treatment dose calculations based on the delivered beamlet sequence to evaluate the results in terms of dosimetric coverage and margin loss. The margin loss is calculated as the maximum difference between the distance from the Clinical Target Volume (CTV) contour to the 97% isodose contour in the treatment plan and the on the film. The dosimetric coverage is defined as the percentage of voxels within the CTV that lies within 97% and 130% of the prescribed dose. As shown in the table below, a margin loss of less than 3 mm for all targets and 100% CTV coverage was achieved. After treatment interruptions, the PET safety evaluation based on the PET pre-scan helped to determine whether the treatment could be continued on the same day using the same injected PET activity (an NTS value ≧ 2 and AC value ≧ 5 kBq/ml). This study demonstrated that the BgRT system is able to deliver the prescribed dose to all targets with independent motion, even when an interruption and resumption occurs during treatment. In case such an interruption if the remaining PET activity satisfies the BgRT safety evaluation, the treatment can continue to deliver the remainder of the BgRT doses. [ABSTRACT FROM AUTHOR]

We present the first dosimetric measurements of single session, multi-target BgRT deliveries using a clinically realistic motion phantom on a research-only version of the RefleXion X1 system. A custom-made anthropomorphic phantom of a human torso with embedded fillable targets mimicking 18F-FDG-avid lesions was used. From the three embedded spherical targets, Target 1 was 26 mm in diameter coupled with a 3D independent respiratory motion with 22 mm range, whereas Target 2 and 3 were 22 mm in diameter and moved with a 1D 5 mm maximum sinusoidal motion. The 18F-FDG concentration in the background cavity of the phantom was 5 kBq/ml, and the targets were loaded with 10:1, 8:1 and 6:1 contrast relative to the background for Targets 1, 2, 3, respectively. Spherical structures were contoured as GTVs (CTV = GTV) and a 5 mm margin was added to create PTVs. Motion extent of the tumors were captured to create biological tracking zones for each target. Treatment plans were generated using a research version of the Reflexion treatment planning software to deliver 8 Gy/fx to the PTVs. The treatment delivery was repeated 2 times, and each time the phantom was refilled according to the plan. PET image evaluation metrics for each of the three targets were also recorded. Target dosimetry was measured using a combination of radiographic film and ion chamber. The maximum distance between the 97% prescription isodose line from the plan and the film measurements was used to characterize the dosimetric accuracy of the tracked deliveries. CTV and PTV min, max, and mean doses measured on film were also recorded for each target. Treatment plans were successfully created with 100% prescription dose coverage to each target loaded with different FDG ratios. Total treatment times for the single-plan, three-target deliveries were less than 80 minutes. PET evaluation metrics at imaging-only and pre-scan, and planning and film dosimetry to the GTV and PTV for each of the three targets is shown in table below (mean ± standard deviation of both deliveries). The CTV dose coverage was maintained for all targets. The shrinkage distance of the 97% prescription dose isodose line on the film plane for all three targets was less than 3 mm for both tests, and ranged from -0.4 to -2.34 mm. These results demonstrate that high tracking accuracy and dosimetric accuracy can be achieved in single session, multi-target deliveries over a range of target-to-background 18F-FDG concentrations and target motion patterns. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Biology-guided radiotherapy (BgRT), utilizes hardware that incorporates a PET detection system into a ring-gantry LINAC for real-time tracking delivery. For this study, we focus on the BgRT delivery performance in the case of static targets for dose accuracy measurement. During active beam delivery, the system operates by aiming beamlets of therapeutic radiation at malignant tumors in response to outgoing PET emissions with sub-second latency. Over a treatment fraction, these beamlets sum to the total intended dose prescribed by the physician. Physical demonstration of BgRT has not previously been reported. Here we report phantom experiments validating BgRT using static PET-avid targets of varying shapes and background PET environments.Materials/methods: An FDG-fillable insert with different shaped targets was developed to mimic different potential radiotherapy targets. Spherical and C-shaped targets were filled with 18F-flurodeoxyglucose (FDG) to represent tumors and/or organs-at-risk. The background material in the insert was either a homogenous water medium or a water filled heterogeneous medium with a Styrofoam mesh simulating lung tissue surrounding the target. Targets and OARs were filled with FDG to achieve a target/OAR: background ratio of 8:1, while the background concentration varied from 4.5-10 kBq/ml to simulate typical patient background activity concentrations. For our set-ups were investigated: Spherical target in homogenous background, spherical target in heterogeneous background, C-shaped target in homogenous background, and spherical target in homogenous background with nearby PET-avid, C-shaped OAR. For each combination, SBRT and BgRT treatment plans were created on the RefleXion treatment planning system (TPS). Next, SBRT and BgRT plans were delivered on a pre-commercial version of the RefleXion system and dosimetric accuracy was measured using the AC phantom. Gamma criteria (3%/3mm) were used to compare delivered and calculated dose. Paired Student's t-test assessed differences in SBRT and BgRT gamma pass results.Results: All BgRT deliveries met 3%/3mm gamma pass criteria greater than 95% (Range, 95.2% to 98.9%). Additionally, gamma passing rates were not significantly different than the companion SBRT plans performed on the same targets (P = 0.16).Conclusion: Dose accuracy results indicate that BgRT plans can be delivered accurately over a variety of test conditions (different target shapes, attenuating media and activity concentration levels) to FDG-avid targets, with performance similar to SBRT treatments. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): A biologically guided radiotherapy (BgRT) system was developed and equipped with a novel O-ring gantry Linac, positron emission tomography (PET) and computed tomography technologies. This architectural design is to support real-time PET-guided treatment, termed biology-guided radiotherapy. To reduce latency between PET data acquisition and radiation delivery, the BgRT system incorporates a fast-transitioning binary multi-leaf collimator (MLC) leaves sandwiched between a split-jaw. This study reports the dosimetric commissioning of the first clinical BgRT machines at our institution, and compared with the reference data provided by the manufacturer.Materials/methods: The dosimetric commissioning of the 6 MV flattening filter-free (FFF) photon beam was characterized using a 3D water phantom and diode detectors at a source to surface distance of 85 cm. In-air profiles of 40cm x 2cm field, 40cm x 1cm field, and various leaf combinations plus in water PDD data of 12 field sizes (1.25, 2.5, 5, 10, 20 and 40 cm MLC opened leaves with 1 and 2cm jaw settings) were acquired first for beam modeling. Additional longitudinal and transverse profile scans were performed for these 12 field sizes at the depth of 1.5, 5, 10, 15 and 20 cm to verify the beam model accuracy. The relative outputs factors were measured with the W2 1mmx1mm scintillator at the depth of 10cm for the field sizes from the smallest 0.6cm x 1cm to the maximum 40cm x 2cm.Results: For the PDDs of reference field size of 10cm x 2cm measured at Stanford, the maximum doses (dmax) were 12.5mm within the manufacturer's reference range of 13 ± 0.75 mm. The percentage doses at 10cm depth (d10) at reference field size were 56.9% and 57.6% for Stanford and RefleXion measurements, respectively. The longitudinal field sizes for all tested fields were agreed within 0.5mm and the transverse off-axis ratio is within 1% in the beam core (80% of nominal field size). The output factors measured at our institute were ranging from 0.706 to 1.012 relative to the reference 10cm x 2cm field.Conclusion: This evaluation represents the first commissioning evaluation of the dosimetric characteristics of the BgRT system with architecture designed to accommodate both PET detector and LINAC subsystems. This data will serve as a clinical reference for the BgRT treatment planning system's beam model and can act as a standard for comparison and beam model improvement for units installed at future clinical sites. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Biology-guided radiotherapy (BgRT) integrates PET detectors with a LINAC and delivers a real-time tracked dose of radiation to moving targets using a continuous stream of limited time-sampled (LTS) PET images as a biological fiducial. These LTS PET images are converted into fluences and delivered to the target that cumulatively sum to deliver the intended prescription dose to the planning target volume (PTV). Physical validation of BgRT directed at a moving target has not previously been reported.Materials/methods: An 18F-Fluorodeoxyglucose (FDG) fillable insert that fits inside the independent quality assurance tool cavity was used in these experiments. The insert included a 22mm diameter target enclosed within a Styrofoam mesh compartment, simulating a lung-like background. The insert was filled with FDG with a target-to-background ratio of 8:1, placed in the independent quality assurance tool cavity which was then mounted on a custom motion stage that could move in the axial direction (IEC-Y). Motion was simulated using a breathing waveform that had a large amplitude motion (from -14.3 mm to +14.4 mm with respect to the mean position), with random amplitude and period with a baseline shift over time, simulating breathing baseline shifts. A BgRT plan (prescription of 8Gy) was created using motion averaged PET images, acquired on a pre-commercial version of the RefleXion system using a 32 × 32 × 32mm (IEC-X, Y, Z) PTV - 5mm expansion over the clinical target volume (CTV). An internal tumor volume (ITV) based SBRT plan (prescription of 10Gy) with a 32 × 32 × 62mm PTV covering the motion extent was also created. Radiochromic EBT-XD film was inserted into a slot in the spherical target to measure the delivered dose. Using the same motion waveform, BgRT and SBRT plans were delivered to the moving target, with an additional 8Gy BgRT delivery (32 × 32 × 32mm PTV) to the stationary target serving as control. Dosimetric accuracy for moving targets was measured using the concept of coverage where 100% of the CTV receives at least 97% of the prescription dose and maximum dose in the CTV was = < 130% of the maximum planned dose.Results: Under motion, both SBRT (32 × 32 × 62mm PTV) and BgRT (32 × 32 × 32mm PTV) met CTV dose coverage. CTV dose ranges were a) Motion SBRT: measured = [10.4Gy,12.4Gy], plan = [9.7Gy, 17.2Gy], b) Motion BgRT: measured = [9.7Gy,11.2Gy], plan = [7.8Gy, 15.3Gy], c) Static BgRT: measured = [8.7Gy,10.1Gy], plan = [7.8Gy), 10.4Gy]. Motion coverage results indicate that BgRT with a PTV that is 48.4% smaller than the SBRT PTV, delivering a tracked dose to the moving target., indicating a more conformal delivery.Conclusion: This is the first report of BgRT delivery achieving a tracked dose distribution directed at a moving target. Because tracked distributions have better conformality and normal tissue sparing than free-breathing internal tumor volume approaches, BgRT may improve the toxic-therapeutic ratio for applications such as early-stage lung cancer. [ABSTRACT FROM AUTHOR]