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Sonic hedgehog (SHH) is a protein that differentiates the floor plate cells in the neural tube and the motor neurons. Different concentrations of amino-terminal product of sonic hedgehog (SHH-N) autoproteolytic cleavage induce differentiation in the floor plate cells and the motor neurons. High concentration of SHH-N induces only floor plate cells differentiation and has no effect on the motor neurons and low concentration induces differentiation in the motor neurons. Notochord processing of sonic hedgehog into SHH-N induces floor plate and motor neuron in vitro.

Biology-guided radiotherapy (BgRT) is a novel platform that combines real-time PET imaging with a 6MV Linac to target tumors. The performance and safety of BgRT was assessed in the BIOGUIDE-X clinical trial. This study aims to report on the BgRT workflow steps and assess the time required for each step of the BgRT process during this trial. A total of nine patients were enrolled in the second Cohort of the BIOGUIDE-X study which included patients treated with stereotactic body radiotherapy (SBRT) for lung tumors (5) and bone tumors (4). The pre-treatment BgRT workflow includes CT simulation, contouring, imaging-only (BgRT Modeling) PET acquisition, BgRT planning, patient specific QA and plan approval. The imaging-only PET acquisition on the X1 collects a representative PET volumetric 3D image and is an input to develop the BgRT treatment plan. The steps during the BgRT delivery session are kVCT localization, PET pre-scan, PET evaluation and BgRT delivery. The PET PreScan is a 1-pass short-duration PET acquisition that is used to confirm that the PET biodistribution on the day of treatment is consistent with that of the imaging-only PET. During BIOGUIDE-X, the BgRT delivery step was replaced by a 4-pass long-PET acquisition that was used to emulate the expected BgRT dose distribution without turning the beam on. To assess BgRT workflow, times from 18F-FDG injection to image-only PET acquisition, 18F-FDG injection to PET pre-scan, Pre-scan to PET evaluation, and PET evaluation to BgRT delivery (long PET acquisition) were recorded. Time between the 18F-FDG injection and the X1 imaging-only PET scan was 84 ± 19 minutes which includes time for 18F-FDG update. Average time to perform imaging-only PET scan was 26 ± 4 minutes. During the BgRT 'delivery' session, the mean time between the kVCT acquisition and PET pre-scan acquisition was 7 ± 3 minutes. The mean time to acquire a 1-pass PET pre-scan was 6 ± 1 then followed by 6 ± 1 minutes for the PET pre-scan dose calculation to estimate the BgRT doses that it would have delivered for this fraction. On average, the PET reconstruction, the PET signal localization verification and the evaluation of safety metrics took 11 ± 4 minutes. The mean time for BgRT 'delivery' was 27 ± 5 minutes based on the 4-pass long PET acquisition. Time from the start of the BgRT session to the end of the BgRT 'delivery' with this version of the investigative product release was 65 ± 9 minutes. The new processes introduced by the BgRT technology were evaluated and found clinically feasible. Improvements are being undertaken to shorten the time required for each step and to increase patient comfort ahead of BgRT clinical implementation. [ABSTRACT FROM AUTHOR]

For patients with metastatic cancer and their doctors, prognosis is important for choosing treatments and supportive care. Oncologists' life expectancy estimates are often inaccurate, and many patients are not aware of their general prognosis. Machine learning (ML) survival models have become accurate and could be useful in the clinic, but there are potential concerns involving accuracy, provider training, and patient involvement. We conducted a qualitative study to learn about patients' and oncologists' views on these issues. In this Institutional Review Board-approved study, patients with metastatic cancer and their family members, radiation oncologists, and medical oncologists were recruited from a single academic health system. Semi-structured interviews were conducted using a script. Participants were shown an anonymized report from a validated ML survival model that included a predicted Kaplan-Meier survival curve and a list of the top features increasing and decreasing predicted survival. Fifteen patients, five radiation oncologists, and five medical oncologists were enrolled. Patients ranged in age from 54 to 87, with head and neck being the most common primary site (n=8). Physicians practiced in both hospital-based and community outreach clinics, were either generalists or specialized in a specific disease site, and ranged in years of practice from 5 to 29. Six patients (40%) had discussed their prognosis with a physician. Six (60%) of the 9 patients who had not discussed their prognosis with a physician stated they wanted to have this conversation. Of the 14 patients who completed the full interview, all wanted the option to have the model used in their care, and 11 (79%) believed they had the right to know if the physician used it. 11 (79%) stated they would want to see the report if the model was run on them. All 5 medical oncologists, and 3 (60%) radiation oncologists said they typically inform patients if their cancer is incurable, usually at the first visit. Four of ten physicians (40%) typically discuss detailed prognosis. All physicians interviewed said they thought the ML model was valuable and would want the option to use it in clinic. Only 1 (20%) radiation oncologist believed patients should be notified if their physicians used the model, compared to 4 (80%) medical oncologists. Detailed thematic analysis will be presented at the meeting. Patients and physicians were supportive of the use of an automated prognostic model in their care. Most patients wished to have conversation about prognosis, although only a minority of oncologists routinely discuss prognosis. These data demonstrate a need for oncologists to be more willing to have these conversations and suggest a role for ML models to help facilitate them. [ABSTRACT FROM AUTHOR]

Biology-guided radiotherapy (BgRT) is a novel tracked dose delivery modality using real-time positron emission tomography (PET) to guide radiotherapy beamlets. The present study was performed with sequential cohorts of participants to evaluate the performance and safety of BgRT. Primary endpoints were previously reported. We hereby report on one of the secondary endpoints assessing a novel treatment planning machine with integrated dual kVCT/PET imaging ("novel device") performance in comparison to a third-party diagnostic PET/CT scan. This single-arm, open-label, prospective study included participants with at least 1 FDG-avid targetable primary or metastatic tumor (≥2cm and ≤5cm) in the lung or bone. PET imaging data were collected on the novel device and on a third-party diagnostic PET/CT performed in sequence once at the planning timepoint in Cohort I, and immediately before the last fraction among patients undergoing stereotactic radiotherapy in Cohort II. Three central read radiation oncologists (CRRO) provided an interpretation of the novel device PET scans which were compared to an agreement standard based on 3 central radiologists' review of the paired diagnostic PET/CT scan. Positive percent agreement for localization of the target tumor within the biology-tracking zone (BTZ) was the key metric because it reflects whether advancing patients to subsequent steps in the BgRT workflow based on the novel device's imaging was ultimately appropriate. In Cohort 1, 6 image comparisons were performed. The positive (%) agreement for the aggregate radiation oncologist review was 100% (5/5), reflecting that in all 5 cases where the aggregate radiation oncologists deemed the tumor to fall within the BTZ based upon the novel device PET images, the central radiologists came to the same conclusion upon review of the paired diagnostic PET/CT images. The overall (%) agreement for the aggregate radiation oncologist review was 83.3% (5/6): localization was not established on the novel device in 1 case, even though it was established on the diagnostic PET/CT. This would not pose risk in real world practice as BgRT candidacy would be aborted for tumors not visible on the novel device. In Cohort II, among the 7 image comparisons, there was 100% positive percent agreement between the aggregate CRRO and the agreement standard as the localization criteria was met in both scans for all 7 patients. This was concordant with a 100% overall percent agreement. This investigation demonstrated a 100% positive percent agreement between central review of this novel device images by radiation oncologists and central review of the accompanying third-party PET/CT images by radiologists. There were no cases where a positive localization by the aggregate CRRO was not confirmed by the third-party PET/CT standard, providing evidence against the likelihood of falsely positive localizations on the novel device that would inappropriately advance patients in the workflow. [ABSTRACT FROM AUTHOR]

Despite efforts to increase participation of diverse communities in clinical trials, ethnic/racial minorities remain underrepresented. One such determinant may be lack of access to a comprehensive cancer center that conducts clinical research. Historically, our institution has had low accrual from rural regions further away from our cancer center, with Hispanic or Latino (HL) patients (pts) being especially underrepresented in our clinical research. In this study, we explored the impact of a clinical trial that allowed pts to receive chemotherapy (chemo) with their local oncologist. We hypothesize that allowing pts to receive chemo locally will lead to higher rates of enrollment from populations under-represented in clinical trials. We conducted a study for pts with rectal cancer to undergo short-course radiation followed by 4 months of chemo with the option to pursue watch and wait if pts achieve a clinical complete response. Radiation was administered at our institution while pts could receive standard-of-care chemo closer to home with their local oncologist. For pts who received chemo locally, the research coordinator and co-investigators held video visits with the pts prior to each chemo infusion to review adverse events (AE), labs, and chemo dosing. We compared demographic data of pts on this trial with that of pts enrolled across all adult therapeutic oncologic clinical trials over the same time period at our institution. Distance to our institution was calculated based on pts' primary residence zip code. Protocol compliance with AE reporting for pts who received chemo locally was assessed by chart review. Between May 2020 and January 2023, 24/35 enrolled pts completed both radiation and chemo on trial. 13/24 pts (54%) received chemo locally. Of the 24 pts, 16 were White (67%), 7 Asian (29%), 1 Native Hawaiian/ Pacific Islander (4%). Of all enrolled patients, 4 were HL (16.7%), compared to our institutional average of 16.5%. All enrolled HL pts received their chemo locally. The average distance traveled by non-HL pts from their home to our institution was 87.7 miles (range 5.1 – 308). In contrast, HL pts traveled an average of 147.8 miles (range 110 – 249), 68% further than their non-HL counterparts. There was 100% compliance with AE reporting among those pts who received their chemo locally. Although the percentage of HL participation in our study was consistent with our institutional average, all HL pts enrolled on the trial received treatment locally and lived substantially further from our institution than non-HL. By allowing pts to receive this part of treatment locally, we provided pts who live further away an opportunity to engage in clinical research without the associated financial and time toxicities related with traveling for treatment. By decentralizing clinical trials and leveraging telemedicine, we can promote the participation of under-represented groups in clinical trials. [ABSTRACT FROM AUTHOR]

Radiation therapy (RT) for localized pancreatic ductal adenocarcinoma (PDAC) remains controversial, with conflicting data likely resulting in variable practice patterns. The Canopy Cancer Collective (CCC) is a learning health network of 14 institutions with high-volume multidisciplinary PDAC teams. To characterize the current state of RT for PDAC at high-volume, academic centers, radiation oncology faculty at CCC member institutions were surveyed. A survey focusing on RT practice patterns for localized PDAC was distributed to 18 faculty with expertise in gastrointestinal RT at CCC sites. Survey results are descriptively reported. The survey was completed by 17/18 (94%) faculty. Among respondents, the number of localized PDAC patients treated per year with RT included >50 (n=5, 29%), 26-50 (n=8, 47%), 10-25 (n=3, 18%), and <10 (n=1, 6%). Two (12%) respondents reported that they routinely offer pre-operative RT for resectable PDAC. Majority of respondents (n=15, 88%) indicated that pre-operative RT is offered to certain patients with borderline resectable pancreatic cancer (BPRC), but the specific proportion of BRPC patients receiving pre-operative RT was variable across respondents (median 70%, range: 10-100%). Similarly, majority of respondents (n=16, 94%) indicated that RT is offered as definitive treatment for certain patients with locally advanced pancreatic cancer (LAPC), but the specific proportion of LAPC patients receiving RT was also variable (median 80%, range: 20-100%), as was the estimated proportion of LAPC patients who eventually undergo resection (median 25%, range 2-50%). Table 1 summarizes the distribution of preferred planning techniques and target volumes used by respondents in both the pre-operative and definitive settings. Variation was also seen in use of fiducials (n=12, 71%), preferred motion management strategy (breath-hold: n=12, 71%; gating: n=5, 29%), systematic use of adjunctive imaging beyond CT for target delineation (MRI: n=6, 35%; PET: n=3, 18%), and use of prophylactic anti-emetics (n=5, 29%) and proton pump inhibitors (n=11, 65%). RT practice patterns for the treatment of localized PDAC remain disparate, with significant variation in institutional standards across stage of disease as well as in basic treatment parameters such as prescription dose and target volume design. A better understanding of the basis for such variation may help guide future avenues of study. [ABSTRACT FROM AUTHOR]

Although arterial phase enhancement is commonly used to evaluate treatment response for hepatocellular carcinoma (HCC), it may not accurately describe response for lesions treated with stereotactic body radiation therapy (SBRT). We aimed to describe the post-SBRT imaging findings to better understand the kinetics of radiographic resolution of HCC and to better inform the optimal timing of salvage therapy after SBRT. We retrospectively reviewed the records of patients with HCC treated with SBRT from 2006 to 2021 at a single institution with available triphasic imaging. We included lesions with characteristic arterial enhancement and portal venous and delayed venous phase washout on initial staging scans. Patients were then stratified into three groups based on treatment: 1) concurrent SBRT and TACE, 2) SBRT only, and 3) SBRT followed by early salvage therapy due to persistent enhancement. Overall survival (OS) was analyzed with Kaplan-Meier, and cumulative incidence of local failure (LF) was calculated with competing risk analysis with death. We included 82 liver lesions in 73 patients. Median follow-up time was 22.3 months (range 2.2-88.1 months). Median time to OS for the entire cohort was 43.7 months (95% CI 18.1-57.6 months) and median progression free survival was 9.5 months (95% CI 6.3-14.0 months). There are a total of 11 (13.4%) lesions that experienced LF in the entire cohort, and cumulative incidence of LF was not significantly different between the 3 groups (p =0.3257). In the SBRT only group, the median time to resolution of arterial enhancement and washout was 5.3 months (range 1.6-23.7 months). At 3, 6, 9, and 12 months, 82%, 41%, 13%, and 8% of lesions continued to show arterial hyperenhancement. Tumors treated with SBRT may continue to exhibit persistence of arterial hyperenhancement. Without an increase in size of enhancement, continued surveillance, rather than early salvage therapy, may be appropriate for these patients. [ABSTRACT FROM AUTHOR]

The first clinical biology-guided radiation therapy (BgRT) system – RefleXionTM X1 - was installed and commissioned for clinical use at our institution. This study aimed at evaluating the treatment plan quality and delivery efficiency for IMRT/SBRT cases without PET-guidance. Forty-two patient plans across six cancer sites (conventionally-fractionated lung, head and neck, anus, prostate, brain, and lung SBRT) planned with the EclipseTM treatment planning system (TPS) and treated with either a TrueBeam® or Trilogy® were selected for this retrospective study. For each Eclipse VMAT plan, two corresponding plans were generated on the X1 TPS with 10 mm jaws (X1 10mm) and 20 mm jaws (X1 20mm) using our institutional planning constraints. All clinically relevant metrics in this study, including PTV D95%, PTV D2%, Conformity Index (CI), R50, organs- at-risk (OAR) constraints, and beam-on time were analyzed and compared between 126 VMAT and RefleXion plans using paired t-tests. All but three planning metrics were either equivalent or superior for the X1 10mm plans as compared to the Eclipse VMAT plans across all planning sites investigated. The Eclipse VMAT and X1 10mm plans generally achieved superior plan quality and sharper dose fall-off superior/inferior to targets as compared to the X1 20mm plans, however, the X1 20mm plans were still considered acceptable for treatment. Strong correlation was observed between the TPS-calculated beam-on time and PTV length in the superior-inferior direction for the X1 10mm (R 2 = 0. 87) and X1 20mm (R 2 = 0. 85) plans. On average, the required beam-on time increased by a factor of 1.6 across all sites for X1 10mm compared to X1 20mm plans. Clinically acceptable IMRT/SBRT treatment plans were generated with the X1 TPS for both the 10 mm and 20 mm jaw settings. The X1 10mm plans were equivalent or superior to the Eclipse VMAT plans, however the beam-on times were longer. [ABSTRACT FROM AUTHOR]

Recent randomized trials have supported the existence of a limited metastatic disease state that may benefit from definitive local therapy in patients with non-small cell lung cancer (NSCLC). Due to limits of current staging systems, it is not possible to evaluate the spectrum of metastatic disease with commonly used cancer registries. The purpose of this study is to evaluate the extent and burden of metastatic disease in NSCLC patients presenting to an academic medical center and determine the incidence of patients meet existing criteria for 'oligometastatic' disease. An observational cohort of patients with de novo or recurrent metastatic NSCLC diagnosed from 2016 to 2019 were randomly sampled from a tumor registry. Patients were excluded if they did not receive any tumor directed therapy. Baseline demographic, staging, and treatment data were obtained from the registry and structured electronic health record (EHR) data. Manual chart review was performed to obtain details on metastatic presentation, local therapy, and progression. Definitions for oligometastatic disease were obtained from NRG LU002, MDACC Gomez et al., SINDAS and SABR COMET clinical trials. One hundred eight patients were evaluated with a median age of 68 years (range, 22 – 92) at initial diagnosis and median follow up of 23.5 months. 75% of patients (n=81) presented with de novo metastatic disease, while 25% (n=27) presented with recurrence. Histologies included adenocarcinoma (66%, n=71), squamous cell carcinoma (9%, n=10), and 'other' (20%, n=22). Targetable mutations were present in 31% (n=34) of patients including EGFR (n=27) and ALK (n=2) and MET (n=6). 41% (n=48) of patients had a suspected malignant effusion present at the time of diagnosis. Common sites of metastases included lymph nodes (n=85, 79%), lungs (n=60, 56%), brain (n=49, 45%), and bone (n=48, 44%). 19% (n=21) presented with only one total metastatic tumor, 29% (n=31) with 2-3, 17% (n=18) with 4-5, 19% (n=21) with 6-10, and 16% (n=17) with 10+ tumors. 28% (n=30) of all patients were eligible for at least one oligometastatic NSCLC clinical trial, with 16% meeting eligibility for LU-002 (n=17), 19% for MDACC (n=22), 16% for SABR COMET (n=17), and 5% for SINDAS (n=5). Among those that met trial criteria for oligometastatic disease 40% (n=12) were treated with local therapy including surgery or radiation. Most patients presenting with metastatic NSCLC to our institution had initial de novo metastatic presentation, multi-organ involvement, and adenocarcinoma histology. Roughly one third of patients were classified as oligometastatic using existing trial criteria. A minority of oligometastatic patients were treated with local therapy after metastatic diagnosis during the study period. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): The first clinical biology-guided radiation therapy (BgRT) system - RefleXion X1 - is installed and is being commissioned for clinical use at our institution. The system delivers 6MV-FFF beam via 50 firing positions at 850 cGy/min dose rate on 60 rpm rotating gantry with the couch advancing in 2.1 mm increments. Collimation is achieved through a binary multi-leaf collimator system composed of 64 (6.25 mm width at 850 cm SAD) leaves and 10mm or 20mm jaws. The purpose of this study was to compare the treatment plan quality and delivery efficiency for SBRT cases without PET-guidance.Materials/methods: Five lung cancer patients (50 Gy/4fx) with motion-inclusive PTV previously treated with VMAT SBRT were selected for this retrospective study. For each VMAT plan a corresponding plan was generated on the RefleXion treatment planning system (TPS) using our institutional planning constraints. VMAT SBRT plans used 1-2 partial arcs with 10MV-FFF energy and 2400 MU/min dose rate. RefleXion SBRT plans used all 50 firing positions and 1 cm jaw collimation. As plan normalization option does not yet exist in the RefleXion TPS, the plans were optimized to achieve PTV D95% coverage with 100% of prescription dose to the best of planner's ability. All clinically relevant metrics in this study, including plan PTV D95%, PTV D1%, 50% isodose volume (I50%), Conformity Index (CI), organs at risk constraints, and treatment time were analyzed and compared between VMAT and RefleXion plans using paired t-tests.Results: Clinically acceptable plans were obtained with both techniques. The average PTV volume was 14.1 ± 6.4cc. For VMAT and RefleXion plans, no statistically significant difference was observed in PTV D95%, PTV D1%, CI or I50%. Ipsilateral lung volume spared at 12.4 Gy (VS12.4) was slightly greater (31.6cc increase, P < 0.035) and skin Dmax was slightly lower (1.4 Gy decrease, P < 0.038) for RefleXion plans. Treatment beam-on time was significantly longer for RefleXion plans (23.4min increase, P < 0.0002).Conclusion: RefleXion TPS provided comparable plan quality to lung SBRT VMAT plans. Treatment beam-on time is significantly longer for the RefleXion system. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): A novel therapeutic machine that combines PET, fan beam kVCT and linear accelerator to support real-time PET-guided treatment, termed biology-guided radiotherapy (BgRT). This study reports the positioning accuracy, image quality, and dose commissioning of the kVCT imaging system of the first clinical BgRT machine at our institute.Materials/methods: The helical fan-beam kVCT subsystem consists of an X-ray tube with a voltage of 120kV and a 16-row GOS Ceramic Scintillator detector. The gantry rotation speed is 60 rpm. The tube currents are 45, 67, 133mA for 0.5 pitch; 100, 150, and 300mA for 0.5 pitch; 267 and 400mA for 1.333 pitch. The image slice thickness is 1.25mm with a field of view of 500mm and a resolution of 512 × 512. A ball-cube phantom was used to test the positioning accuracy of the kVCT subsystem with respect to the setup laser and MV beam. Catphan504 phantom was imaged with 0.5 pitch and 150mAs to test the kVCT image quality of the BgRT system, including the uniformity, noise, HU constancy, spatial resolution, geometric distortion, slice thickness, and low contrast visibility and detectability using the PIPSproTM software. The RTI MAS-2 and Piranha detectors were used to verify the accuracy of the mA and voltage. The CTDI dose was measured using a CTDI phantom and a Standard Imaging A101 pencil chamber.Results: The localization error of the ball cube phantom was -0.8, 0.9, and 0.3mm in IEC x, y, and z directions, respectively. For the Catphan504 tests, the vertical and horizontal uniformities were 0.926 and 0.857, respectively. The HU constancy tests of the air, water, polystyrene, acrylic, Delrin, Teflon were all within 40HU to the expected values. The modulation transfer function test results were 0.467, 0.528, and 0.595 lp/mm for F50, F40, and F30, respectively, which showed a comparable spatial resolution to regular CT simulators. The geometric distortion was 0.12mm and slice thickness inaccuracy was 0.13mm. The low contrast detectability was 0.734. The measured mA and voltage were within 5% of the nominal setting of 120 kV and 150 mA. The CTDIw was less than 1.4 cGy for body and 3 cGy for head with a protocol of 120 kVp, 150 mAs, and 1.25 mm slice thickness.Conclusion: This evaluation represents the kVCT characteristics of the novel BgRT system with architecture designed to accommodate CT, PET and a LINAC. The image quality and HU constancy are comparable to our CT simulators and is a useful tool for online adaptive radiotherapy. The commissioning data will serve as a standard for units installed at future clinical sites. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): The X1 system ("X1") integrates a fully functional Positron Emission Tomography (PET) combined with a fan-beam kVCT system into the architecture of a ring-gantry linear accelerator (LINAC) for biology-guided radiotherapy (BgRT) delivery. The integration of PET into a LINAC framework required design features that deviate from the diagnostic setting. For instance, the X1 houses two opposed 90° PET arcs that rotate at 60 RPM to generate sinogram reconstructed images rather than a static, circumferential array of detectors. To better understand X1 PET performance, we conducted a side-by-side comparison of images of a PET phantom obtained sequentially on the X1 PET subsystem and a traditional PET/CT scanner.Materials/methods: An independent quality assurance phantom utilized a custom insert with two-insert targets filled with 18F-fluorodeoxyglucose (FDG) diluted water. Spherical target had a diameter of 22 mm and C-shape geometry consisted of an active volume of 26mm axial length and 255-degree partial annulus with major and minor radii of 27 mm x 12 mm, respectively. The targets were filled with an activity concentration of 9.3 kBq/ml to achieve a target to background ratio of 8:1 simulating the target uptake with hot background in a patient. The phantom was imaged within 30 minutes of preparation on the X1 PET and then immediately transferred to a PET/CT Biograph scanner for a second image. This experiment was repeated three times in separate days to assess reproducibility of PET acquisition. The PET images were visually assessed by the radiation oncologists to ensure the PET signal is within PTV. The PET signals of the targets were also evaluated using the full-width-half-max (FWHM) calculated on left-right (RL), anterior-posterior (AP) and superior-inferior (SI) directions for both targets and compared to the physical dimensions of the cavities.Results: The imaging acquisition tests were successfully completed on all three days for both systems, as per the prescribed workflow. In all experiments, radiation oncologists verified that the PET avid area were within the PTV in both systems. Average FWHM results of the 22 mm spherical target on X1 PET were 24.5, 21.7 and 17.0 mm as compared to 20.0, 20.0 and 18.2 mm for PET/CT in LR, AP and SI directions, respectively. For the C-shape object X1 PET resulted in 18.8, 19.5, 21.8 and 25.0 mm whereas the PET/CT resulted in 12.7, 13.2, 13.2 and 24.7 mm FWHMs for the two RL C-shape legs, AP and SI directions, respectively as compared to 15-, 15-, 15- and 26-mm physical dimensions.Conclusion: The X1 PET subsystem - which utilizes dual PET arcs and a sinogram image reconstruction algorithm in order to integrate into a LINAC architecture - generates images that are qualitatively comparable to a traditional PET scanner. In general, X1 FWHM results were slightly larger and PET/CT ones were smaller than the physical dimensions in axial plane. Both systems slightly underestimated the target size in SI direction. [ABSTRACT FROM AUTHOR]

Highlights: [•] We created a dataset of chemicals in consumer products (CP) using public data. [•] Nearly 1800 unique substances in 350 generic CP use categories were identified. [•] Generic CP formulations inform individual product compositions. [•] We identified clusters of trace, intermediate and ubiquitous chemical exposures. [•] Overlap with 70% of NHANES classes points to CP as a major chemical exposures source. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): To evaluate Biology-guided Radiotherapy (BgRT) plans generated using PET data acquired on the first installation of the Reflexion™ X1 system. BgRT treatment planning optimizes for fluence indirectly by calculating firing filters that best translate the X1 acquired PET image to the fluences that deliver the prescribed radiation dose. During a treatment session, the firing filters are applied to limited time sampled (LTS) PET images to calculate delivery fluences.Materials/methods: An FDG fillable phantom insert that consists of a 22 mm diameter spherical target (PTV1, ball) and a C-shape object (PTV2 with 26mm axial length, 255° partial annulus with major and minor radii of 27 mm and 12 mm) was imaged using a CT Simulator to create planning contours. The water filled insert surrounding these objects was filled with FDG to simulate a warm background. Both targets were filled with FDG, simulating a target to background ratio of 8:1. Two different BgRT treatment plans were generated for PTV1 simulating homogenous uptake, and PTV2 with an inhomogeneous FDG uptake due to necrosis (a cylinder encompassing the C shape PET avid object). A structure that is 12.5 mm away from these targets was used to simulate OAR. Two PET/CT imaging acquisitions were performed on the RefleXion X1 masking the signal outside of each target plus 10 mm margin. Two different BgRT plans were generated prescribing 50 Gy delivered in 5 fractions to each target, separately. The quality of each treatment plan was evaluated based on PTV coverage, Conformity Index at 50% and 80% isodose lines (CI50, CI80) and OAR sparing. Both BgRT plans then delivered to the independent quality assurance tool for patient specific QA verification where the 3%/3 mm gamma criteria was used.Results: BgRT plans for both homogenous and heterogenous FDG uptake targets were created successfully. Prescription dose coverages were 94.2% and 96.3% for PTV1 and PTV2, respectively. The maximum OAR doses were 30.9 and 33.0 Gy and average OAR doses were 14.4 and 20.1 Gy for PTV1 and PTV2 plans, respectively. CI50 were 7.7 and 6.8 where CI80 were 2.5 and 2.6 for PTV1 and PTV2 plans. The patient specific QA passed with 100 % for both plans.Conclusion: This is the first report of the BgRT plan creation and QA delivery using a clinical installation of the Reflexion X1 system, opening the potential towards BgRT dose delivery using the real time FDG uptake measurements to biologically guide active radiation beam delivery. The X1 system was able to optimize and deliver the BgRT plans for both homogenous and heterogenous FDG uptake scenarios. BgRT is a new paradigm of dose optimization, where a new set of optimization and evaluation approaches will be needed. [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]