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BgRT was approved for clinical use and a medical technology company was commissioned for SCINTIX BgRT at our institution. These abstract aims to evaluate the congruence of the measured PET signal during BgRT and the delivered doses for the first two patients treated with BgRT to their lung tumors. Biology-guided Radiotherapy (BgRT) uses PET emissions from the patient to guide the radiotherapy beam to tumor. During delivery of BgRT, while the PET emissions are collected, they are converted into beamlets and delivered to the patient. At the end of this process, a PET image is reconstructed and the delivered dose is calculated for that fraction. Two patients were treated with SCINTIX™ BgRT at our institution, each receiving 50 Gy/4 fractions to their lung tumors. The GTV is contoured in end-expiration phase of the simulation 4DCT and a 5 mm margin was added to generate PTV. The tumor motion extent was captured using the ITV and a 10 mm margin was added to ITV to generate Biological Tracking Zone (BTZ). For each fraction, the mean PET intensity in GTV was measured and used to threshold the signal to find the centroid of PET biodistribution. The 80% isodose line, corresponding to 10 Gy, was converted to a volume and used to estimate the centroid of the delivered doses. The distance between the PET and 80% dose centroids were used to estimate the congruence of the PET signal and delivered BgRT doses for each fraction. For comparison, the BgRT plans were calculated with a grid size of 2.1 mm, and the PET image acquired had a grid size of 4 mm. Both patients were able to complete their course of treatment successfully. For Patient 1, the PET modeling mean PET signal in GTV was 19.5 kBq/ml and it was 22.0, 21.1 18.7 and 18.6 for the 4 fractions. Patient 2 had a PET modeling mean intensity of 18.8 kBq/ml and during the treatments it was 21.0, 14.3, 17.9 and 12.4. A total of eight post-treatment delivered dose volumes were calculated using the fluence patterns delivered by the X1. The mean congruence of the PET and delivered doses for patient 1 was 0.5, 2.0, 0.6 and 1.8 mm whereas the Patient 2 had the delivered doses agree with 1.3, 0.8, 2.7 and 1.4 mm for 4 fractions. From 8 fractions analyzed, the maximum disagreement was 1.0, 2.4 and 1.7 mm in the L/R, A/P and S/I directions. The BgRT doses agreed well with the isocenter of the PET, confirming that the medical technology company system delivered doses for both patients where the PET signal was emanating from. Given the pixel size of the dose calculation (2.1 mm) and the PET pixel size (4.0 mm), the measured agreement provide assurance for the geometric accuracy of BgRT delivery in patients. [ABSTRACT FROM AUTHOR]

For metastatic non-small cell lung cancer (NSCLC), the addition of radiotherapy (RT) to immune checkpoint inhibitor (ICI) therapy could have synergistic anti-cancer effects, or address the most threatening tumors while the immunotherapy provides benefit for the remaining disease. In the Radical RADiotherapy and Immunotherapy for metastatic Cancer of the Lung (RRADICAL) trial (NCT03176173), we posited that the addition of high-dose RT to ICI therapy could prolong progression-free survival (PFS). In this non-randomized single arm phase 2 trial, 45 patients with metastatic NSCLC who received an anti-PD-1/anti-PD-L-1 ICI for 4+ weeks were enrolled from July 2017 to May 2021. Imaging after initiation of ICI had to show partial response or stable disease (per RECIST version 1.1) or modest progression (per investigator). Patients received high-dose RT to 1-4 extracranial tumors and continued the ICI until disease progression or unacceptable toxicity. The primary endpoint was PFS at 24 weeks from enrollment, comparing to a historical control rate of 35%. Secondary endpoints included toxicity, overall survival (OS), and local control. The exact binomial and log-rank tests were used. Of 44 evaluable patients, median age was 71 years, 75% had adenocarcinoma, 64% were poly-metastatic, and 82% were on pembrolizumab. Of 81 treated tumors, the most common dose received was 40 Gray in 10 fractions (n = 41). Forty-six percent of patients had one tumor treated; the most common treatment site was lung. All visible tumors were treated in 21 (48%) patients. Median follow-up was 23.3 months. The trial met the primary outcome: 24-week PFS was 60% (95% CI = 44-75%), higher than the historical control rate (P < 0.001). Median time from enrollment to last dose of the same immunotherapy drug was 6.1 months (IQR = 2.7-12.8 mo). Median PFS was 6.9 months (95% CI = 4.0-13.5 mo) and median OS was 27.4 months (95% CI = 20.4-not reached). Several patients with pre-study disease progression on ICI treatment alone achieved durable responses with addition of radiotherapy, up to 56 months. Local recurrence rate was low: cumulative incidence of 5% at one, two, and three years. Two dose-limiting toxicities were observed (5%), including one grade 5 pneumonitis. Adding high-dose radiotherapy to immunotherapy in metastatic NSCLC improved 24-week PFS compared to historical controls receiving ICI therapy alone, indicating that this is a promising strategy for further study. The excellent local control supports the efficacy of high-dose RT in addressing macroscopic disease in this setting. However, many patients progressed in other non-radiated sites soon after study RT, highlighting the need for better biomarkers for patient selection for aggressive local therapy. [ABSTRACT FROM AUTHOR]

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]

To evaluate post-treatment swallowing function in head and neck squamous cell carcinoma (HNSCC) patients undergoing definitive chemoradiotherapy (CRT) vs. immunoradiotherapy (IRT) using quantitative videofluoroscopic swallow studies (qVFSS). We conducted a cross-sectional study of 23 patients with previously untreated locoregionally advanced HNSCC using qVFSS 4-6 and/or 12-24 months after CRT or IRT. RT consisted of 70 Gy to the primary and 54-63 Gy to the neck in 35 fractions over 7 weeks. Systemic therapy consisted of concurrent cisplatin (N=14) or cetuximab (N=2) in the CRT group and concurrent + adjuvant pembrolizumab only in the IRT group. qVFSS studies were performed by a certified speech-language pathologist using C-arm fluoroscopy with standardized bolus protocol. Quantitative metrics (Pharyngeal Constriction Ratio (PCR), Total Pharyngeal Transit Time (TPT), Bolus Clearance Ratio (BCR), and Posterior Pharyngeal Wall Thickness (PPWT)) were calculated using Swallowtail® software (Belldev Medical LCC, Arlington Heights, IL), with raters blinded to treatment. Higher values of each metric indicate worse swallowing function. For patients undergoing multiple qVFSS, maximum values of each metric were used. Two sample t tests and Mann-Whitney U tests were used to compare metrics by treatment group. Paired t tests were used to compare pre vs. post-treatment qVFSS metrics. Two patients did not complete post-treatment qVFSS, leaving 21 for analysis (16 CRT, 5 IRT). Disease sites were: oropharynx-15, larynx-4, hypopharynx-1, unknown primary-1. Overall mean (SD) PCR, TPT, BCR, and PPWT were 0.15 (0.13), 0.96 (0.27), 14.4 (13.4), and 0.73 (0.24), respectively. Mean post-treatment PCR and BCR were significantly higher for patients receiving IRT vs. CRT (0.21 vs. 0.13, t test p<0.01 and 20.0 vs. 12.7, p=0.019, respectively) (Table). No significant differences were found in TPT or PPWT between groups (Table). Mean (SD) pre-treatment PCR, TPT, BCR, and PPWT were 0.18 (0.19), 0.91 (0.28), 11.6 (11.8), and 0.54 (0.16) respectively. No significant differences were observed comparing post- minus pre-treatment PCR (-0.042, p=0.36), TPT (+0.094, p=0.24), or BCR (+1.38, p=0.54); however, PPWT was significantly worse after treatment (+0.24, p=0.03). Preliminary results indicate dysphagia is worse in patients treated with IRT; however, the analysis is limited by small sample and cross-sectional design. Future studies are needed to define effects of alternative treatments on dysphagia. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) has been associated with prior thoracic radiotherapy. However, AF risk after irradiation of specific cardiac substructures, namely the pulmonary veins (PVs), is still being characterized. We sought to investigate the relationship between PV irradiation and the development of clinically significant (grade≥3) AF (AFG≥3) and determine whether PV dose-volume cutoff values may predict for AFG≥3 risk. We conducted a retrospective study including serial patients who underwent definitive radiotherapy for localized cancers at a single academic institution from 2004-2022, with available dosimetric data. We calculated radiotherapy doses (mean, maximum dose [d max ], and absolute volume receiving ≥15 Gy [V15]) in 2 Gray (Gy) fraction equivalent dose to PVs and other cardiac substructures, including left atrium (LA), sinoatrial node (SAN), and left coronary arteries (LCA tot = left main+left anterior descending+left circumflex). AF incidence was calculated using Fine-Gray with univariable and multivariable analyses clustered by cancer type and adjusted for the competing risk of death to measure adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for AFG≥3 incidence. We used the validated "Mayo AF risk score" ([MAFRS] range, 0-12; greater risk with higher scores) to adjust for clinical factors known to predict for AF. We identified 539 patients with median follow-up time of 58.8 months (range, 0-120). Cancer types included 43% [ n = 230] non-small cell lung cancer, 32% [ n = 174] breast cancer, 22% [ n = 119] Hodgkin lymphoma, and 3% [ n = 16]) esophageal cancer. Baseline factors included a median age of 58 years, 40% male, 52% never-smokers, 59% MAFRS 0-1, 42% PV d max >20 Gy. 35 AFG≥3 events occurred at a median of 22.9 months (range, 0.3-120). AFG≥3 risk was greater among patients with higher PV d max (per Gy; aHR 1.02, 95% CI 1.01-1.03, P<0.001), higher V15 LCAtot (per cm3; aHR 1.14, 95% CI 1.06-1.23, P = 0.001), higher LA volume (per cm3; aHR 1.01, 95% CI 1.00-1.02, P = 0.02). Conversely, AFG≥3 risk was lower among patients with MAFRS 0-1 compared to ≥2 (aHR 0.47, 95% CI 0.23-0.96, P = 0.04) and greater LA d max (per Gy; aHR 0.99, 95% CI 0.98-0.99, P<0.001). The hazard ratio for PV d max remained comparably significant across baseline MAFRS groups (P interaction = 0.14). Higher SAN d max was not associated with AFG≥3 risk (HR 1.01, 95% CI 0.99-1.02, P = 0.36). Finally, in a spline analysis, patients with PV d max >20 Gy (among several potential local maxima identified) had significantly higher risk of AF even when stratified by MAFRS. Pulmonary vein d max , in addition to LCA tot dose, appear to be significant predictors of grade ≥3 AF — regardless of other underlying clinical risk factors. These findings provide new evidence to support the clinical relevance of these cardiac substructures with respect to radiation toxicity, and suggest that PV dose metrics may warrant further validation. [ABSTRACT FROM AUTHOR]

Background Previous studies have found that overestimating treatment effects (i.e. 'optimism bias') leads to underpowered clinical trials. The prevalence of 'optimism bias' in contemporary National Clinical Trials Network (NCTN) cancer clinical trials is unknown. Methods We conducted a systematic review of NCTN phase III randomized trials published from January 2007 to January 2017. We compared the hypothesized versus observed treatment effects in each trial, and examined whether trial-related factors were correlated with the study results. We also reviewed the methods of each protocol to assess whether a rationale for the hypothesized effect size was provided. Results We identified 161 clinical trials, of which 130 were eligible for analysis. Original protocols could not be located for 8 trials (5.0%). Twenty-eight trials (21.5%) observed a statistically significant difference in the primary end point favoring the experimental treatment. The median ratio of observed-to-expected hazard ratios among trials that observed a statistically significant effect on the primary end point was 1.07 (range: 0.33–1.28) versus 1.32 (range: 0.86–2.02) for trials that did not, compared with 1.34 and 1.86, respectively, for National Cancer Institute (NCI) trials published between 1955 and 2006. An effect size at least as large as the one projected in the protocol trials was observed in 9.8% of trials, compared with 17% of NCI trials published from 1955 to 2006. Most trials (64.6%) provided no rationale to support the magnitude of the proposed treatment effect in the protocol. Conclusions Despite a reduction in 'optimism bias' compared with previous eras, most contemporary NCTN phase III trials failed to establish statistically significant benefits of new cancer therapies. Better rationalization of proposed effect sizes in research protocols is needed. [ABSTRACT FROM AUTHOR]

Several studies have noted an increase in the volume of lung tumors treated with stereotactic ablative radiotherapy (SABR) through the course of treatment. The prevalence of such changes and the effect on disease control have not been well studied. Tumor swelling could improve control through immune effects, or worsen it due to geographic miss of the radiotherapy. This is the first study investigating the association between inter-fraction volume changes during lung SABR and clinical outcomes. Patients with AJCC 7th ed. T1-2N0M0 non-small cell lung cancer (NSCLC), who had 4-5 fraction SABR from 4/2009-7/2019 were included in this retrospective study. A planning target volume (PTV) of 5mm was used with motion management as needed. Using cone-beam CT (CBCT) images obtained before each treatment, we contoured each tumor with a standardized procedure in commercially available software. Tumor volumes were assessed prior to initial, midway (third fraction), and last fraction. To explore the relationships between volumetric changes and baseline characteristics, univariable and multivariable linear regression was used. To assess relationship of volume change with outcomes, Fine-Gray models were used with outcomes of local, regional, and distant recurrence, with death as a competing risk. The analysis plan was specified prior to data collection. 121 patients were included. The median ratio of tumor volume at the middle of treatment to start of treatment (Start-Mid) was 1.18 (IQR 1.08, 1.27); the ratio of end of treatment to start (Start-End) was 1.15 (IQR 1.04, 1.28). There was a negative correlation between initial tumor volume and both Start-Mid and Start-End values (p = 0.004 and 0.005, respectively) on univariable analysis. Tumors treated with 50 Gy in 4 fractions (BED 10 112.5 Gy) exhibited larger Start-Mid values compared to those treated with 50 Gy in 5 fractions (BED 10 100 Gy, p = 0.038). Other examined characteristics had no significant correlation with inter-fraction tumor volume changes. Multivariable linear regression analysis reaffirmed a strong correlation between initial tumor volume and both Start-Mid and Start-End changes (p = 0.004 and 0.009, respectively). Fine-Gray models showed no significant correlation between tumor volume changes and local or regional recurrence but found a negative association between Start-Mid change and distant recurrence (p<0.001). Tumor volume often increases during lung SABR. This phenomenon did not appear to adversely affect locoregional control. Increased tumor volume was correlated with reduced distant recurrence, possibly representing an immune effect. Our findings suggest volume changes are likely a consequence of acute inflammatory reactions rather than tumor growth, and modest PTV expansions may be sufficient for tumor coverage. [ABSTRACT FROM AUTHOR]

Stereotactic ablative radiation therapy (SABR) leads to excellent local control in patients with primary or metastatic lung tumors. While there are multiple strategies for motion management in thoracic SABR, there is limited data to compare the efficacy of different approaches. We compared local tumor control by the extent of tumor motion and the motion management strategy for patients treated on the iSABR clinical trial. This is a secondary analysis of patients treated on the multicenter phase II iSABR clinical trial that utilized an individualized dosing strategy for patients with primary or metastatic lung tumors. We evaluated the extent of tumor motion on 4D CT and the motion management approach used during treatment (free breathing, breath hold [BH], or expiratory gating [EG]). For patients treated with free breathing or EG approaches, an internal target volume (ITV) was contoured based on tumor movement on the 4D CT. Patients were treated on a linear accelerator using Real-time Position Management (RPM) triggering. In-field local control rates were compared using the Kaplan-Meier method. In total, 62 patients with 63 tumors had available data on motion management. Fifteen patients (24.2%) underwent SABR with free breathing, 22 (35.5%) had BH (20 inspiratory, and 2 expiratory), and 26 (41.9%) had EG (24 amplitude based, and 2 phase based). 1-, and 2-year local control rates were 100% and 100% with free breathing, 94.7% and 83.2% with BH, and 90.7% and 78.6% with EG (p = 0.2), respectively. Overall, median maximal tumor motion was 10mm (3.5mm for tumors treated with free breathing vs 14.5mm for tumors treated with BH or EG). There was no association between local control and maximum extent of motion on 4D CT (HR = 1.01, p = 0.75). 1- and 2-year local control rates were 92.9% and 89.1% for tumors with maximal motion <10mm, and 96.3% and 82.5% for tumors with maximal motion >10mm (HR = 0.6, p = 0.53), respectively. Patients on the iSABR trial were treated with a range of motion management strategies including motion inclusive free breathing, BH and EG with no observed association between local control by treatment approach. The similar local control rates between mobile and non-mobile tumors suggests that the RPM approach used on the iSABR trial was effective. Our results will be further analyzed pending motion management data collection for the entire iSABR cohort. [ABSTRACT FROM AUTHOR]

Patients (pts) with rectal cancer who achieve a clinical complete response (cCR) after neoadjuvant therapy may be safely observed and spared surgical sequela. We studied a neoadjuvant strategy to increase rates of cCR. We conducted a single arm phase II study of short-course radiation followed by FOLFOXIRI for pts with >T2N0 or low T2N0M0 rectal cancer (NCT04380337). Pts underwent 25 Gy/5 fractions + 5 Gy/1 fraction boost followed by FOLFOXIRI (8 cycles). Primary endpoint of cCR was assessed at 8 weeks following chemotherapy. Those who achieved a cCR or near cCR could be surveilled. cCR required both flat white scar on endoscopy and mrTRG1-2. Assuming a one-sided type 1 error of 0.1, power of 0.9, a null cCR of 0.2 versus an alternate cCR of 0.4, our sample size was 37 pts. Between May 2020 and April 2023, 37 pts enrolled (Table). 25 pts (67.5%) had at least one high risk feature (cT4, extramural vascular invasion [EMVI], N2, threatened circumferential resection margin [CRM], positive lateral node). All pts completed radiation while 32 (86.5%) pts completed all chemotherapy. At primary endpoint assessment, 9 (24%) pts had cCR on both endoscopy and MRI. 14 (37.8%) pts had cCR on endoscopy but residual tumor on MRI: 9 (24.3%) of these pts pursued watch and wait while 5 (13.5%) proceeded to surgery. Of those 9 pts who pursued watch and wait, 5 had local regrowth while 4 had delayed cCR on imaging. Of the 5 pts who went to surgery, all had residual tumor on surgical specimen. All pts who had cCR on MRI also had cCR on endoscopy. In this population with high-risk rectal cancer, 24% achieved a cCR on both MRI and endoscopy at primary outcome assessment. A significant portion of pts had discordant MRI and endoscopy findings, emphasizing the importance of multimodality response assessment and close follow-up for both delayed cCR and local regrowth. [ABSTRACT FROM AUTHOR]

Lung cancer survival is improving in the United States. We investigated whether there was a similar trend within the Veterans Health Administration (VHA), the largest integrated healthcare system in the United States. Data from the Veterans Affairs Central Cancer Registry (VACCR) were analyzed for temporal survival trends using Kaplan-Meier (K-M) estimates and linear regression. 54,922 Veterans were identified with lung cancer diagnosed from 2010-2017. Histologies were classified as non-small cell lung cancer (NSCLC) (64.2%), small cell lung cancer (SCLC) (12.9%), and 'other' (22.9%). The proportion with stage I increased from 18.1% to 30.4%, while stage IV decreased from 38.9% to 34.6% (both p<0.001). The three-year overall survival (OS) improved for stage I (58.6% to 68.4%, p<0.001), stage II (35.5% to 48.4%, p<0.001), stage III (18.7% to 29.4%, p<0.001), and stage IV (3.4% to 7.8%, p<0.001). For NSCLC, the median OS increased from 12 to 21 months (p<0.001), and 3-year OS increased from 24.1% to 38.3% (p<0.001). For SCLC, the median OS remained unchanged (eight to nine months, p=0.10), while the three-year OS increased from 9.1% to 12.3% (p=0.014). Compared to White Veterans, Black Veterans with NSCLC had similar OS (p=0.81), and those with SCLC had higher OS (p=0.003). Lung cancer survival is improving within VHA. Compared to White Veterans, Black Veterans had similar or higher survival rates. The observed racial equity in outcomes within a geographically and socioeconomically diverse population warrants further investigation to better understand and replicate this achievement in other health care systems. [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]

For patients with locally recurrent thoracic tumors or second primaries within previously irradiated volumes, hyperfractionated reirradiation (re-RT) may mitigate late toxicity compared to conventional fractionation, but clinical outcomes have not been extensively studied. We herein report our institutional experience with thoracic hyperfractionated reirradiation. We identified 26 cases among 23 patients treated with re-RT to either primary or metastatic thoracic tumors, 60 Gy in 50 fractions, twice daily over 5 weeks using highly conformal image guided RT with motion management. Nineteen patients had dosimetry data available. The primary outcome was Grade (G2) or higher toxicity rates per CTCAEv5.0. Secondary endpoints were 12-month local control (LC), progression free survival (PFS)—determined by treating physician and/or multidisciplinary tumor board—and overall survival (OS). Median follow-up was 13 months. Half had non-small cell lung cancer, 95.8% had ultracentral tumors, 57.7% had single prior thoracic RT course; 38.5%, 11.5% and 11.5% received concurrent chemotherapy, immunotherapy, and targeted agents, respectively. Minimum and median intervals between RT courses were 10 and 39.5 months, respectively; 94.7% of re-irradiation plans had overlapping 80% isodose volumes. Median OS and PFS were 13 and 10 months, respectively. Crude 12-month LC was 73.1%. Of those with a recurrence, the first recurrence occurred locally in 6 (54.6%), regionally in 3 (27.3%), and distantly in 8 (72.7%) patients. ≥G2 and ≥G3 toxicity rates were 30.8% and 7.69%, respectively (one G3 atrial fibrillation; one G5 pneumonitis). Using the American Radium Society guidelines for thoracic reirradiation, only 10.5% met all dose volume constraint recommendations. Definitive hyperfractionated thoracic re-RT was well tolerated with promising local control. ≥G3 toxicities were rare. Patients should be counseled on the low but potential risk of life-threatening toxicity. Consensus guidelines for dose constraints may be difficult to meet in reirradiation setting; in this cohort, rates of severe toxicity were low despite exceeding putative constraints in most patients. [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]

Minimizing cardiac toxicity after thoracic radiation therapy (RT) remains a clinical challenge. Mean heart dose is associated with major adverse cardiac events (MACE) and recent studies suggest RT dose to coronary arteries may better quantify risk after conformal RT. Prior studies have not evaluated RT dose to individual coronary arteries in risk modeling. We therefore sought to develop an integrated dosimetric model accounting for RT doses received by each coronary artery. We performed a retrospective study of a randomly selected representative cohort of patients with locally advanced non-small cell lung cancer. We scored cardiac events as (1) ischemic, (2) constrictive, (3) valvular, or (4) conductive. We contoured and measured doses received by the left circumflex (LCX), left anterior descending (LAD), left main coronary (LMCA), and right coronary arteries (RCA). RT doses were measured as equivalent dose in 2-Gray (Gy) fractions. Dosimetric parameters associated with cardiac toxicity were examined using cumulative incidence, competing risk regression models, receiver operator characteristic (ROC), and log-rank statistics with significance defined as two-tailed P <0.05. We identified 100 patients who received definitive RT (median=66 Gy, range=60-74 Gy) from 2006-2020. Median follow-up was 4.1 years (range, 0-11.0). Median age was 70 years (range, 38-84). Half the cohort was male (50%), a majority had smoking history (81%), and all received chemotherapy (100%). Thirty (30%) experienced MACE at a median of 13 months post-RT. Most events were ischemic (n=17, 57%) or conductive (n=13, 43%), with only 3 cases (10%) of valvular disease. Mean heart, LCX, LAD, and LMCA doses were predictive of cardiac toxicity (AUC=0.59, 0.58, 0.59, and 0.63, respectively) and were each significantly associated with MACE on univariable analysis (P <0.05). For patients with full labs available, 10-year atherosclerotic cardiovascular disease (ASCVD) risk was also associated with MACE (HR=1.31, P =0.04). Chemotherapy, age, diabetes, hypertension, prior cardiac event, and mean RCA dose were not associated with MACE. Using the log-rank statistic, we identified threshold mean doses of 1.82, 12.71, 15.45, and 31.29 Gy for the heart, LCX, LAD, and LMCA, respectively. Patients exceeding all three threshold doses to the LCX, LAD, and LMCA had a two-year rate of MACE of 57.1% versus 15.9% (P =0.005). On multivariable analysis after adjusting for ASCVD, patients exceeding all identified doses to the LCX, LAD, and LMCA were at nearly 5 times the risk of MACE (HR=4.76, P =0.0005). Our results suggest that patients receiving doses above our identified thresholds to all of the left coronary arteries (LCX, LAD, and LMCA) are at highest risk of MACE. If validated, our findings may inform RT treatment planning, where sparing of at least one vessel may lead to lower risk of MACE. [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]

Radiation oncology generates large volumes of multi-source data that can be harnessed to accelerate personalized cancer care. We describe the implementation of a departmental clinical data warehouse and a case demonstrating application of this tool. Physician stakeholders collaborated with software engineers and developers with domain knowledge in electronic medical records (EMR), cancer registries, and radiation treatment planning systems to design a departmental radiation oncology data warehouse. Data from EMR, radiation treatment planning system, institutional cancer registry, and pathology database were merged by patient medical record number and made accessible via a web application with a graphical user interface (GUI) written in R Shiny and hosted on Shiny Server Pro (RStudio). Data sources are refreshed at weekly to quarterly intervals and extracted to Shiny Server Pro. Team meetings were held every two weeks to refine current data elements, implement process improvements, and improve data quality and integrity. The warehouse can only be accessed by departmental users who have completed data privacy training and attestation under an IRB. Using the data warehouse, we examined radiotherapy fractionation patterns among breast cancer patients in our department. Filters for demographic, prognostic, and treatment characteristics were applied to build cohorts of patients treated with hypofractionated whole breast irradiation (WBI, 2.6-2.7 dose/fraction for 15-16 fractions) and standard fractionated WBI (1.8-2 dose/fraction for 25-30 fractions). The data warehouse includes 66,078 unique patients seen in our department from 4/28/1997 through 12/7/2021. We identified 2,206 patients diagnosed with breast cancer who received WBI between 2010 and 2020. Use of hypofractionation increased from 16% in 2010 to 71% in 2020. Of the patients who received hypofractionated WBI in 2010, median age was 69 years, 89% had Tis (33%) or T1-2, N0 (56%) tumors, and 67% had right-sided breast cancer, compared to 58 years, 86% (13%, 73%), and 48% in 2020, respectively. Among the patients who received hypofractionated WBI and with known hormone receptor status, 100% in 2010 and 80% in 2020 were ER/PR+/HER2-. These large-scale analyses took minutes to execute and yielded hypofractionation trends similar to those in existing studies. We created a clinical data warehouse that includes all patients treated in one radiation oncology department and aggregates health information from different data sources into a centralized and user-friendly, web-based GUI console. We used this resource to efficiently examine WBI fractionation patterns in the warehouse over a 10-year period; work is ongoing to continually improve data quality. By leveraging real-time clinical data for secondary uses, this effort can drive precision cancer medicine by making research, quality assessment, and predictive modeling a natural outgrowth of routine patient care. [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]

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]

Purpose/objective(s): Prior research suggests that radiation oncologist provider experience may influence outcomes for radiation treatment modalities requiring greater technical expertise for given disease sites. We investigated whether institution treatment volume (TV) for SABR technique impacted survival outcomes for patients with NSCLC.Materials/methods: We conducted a retrospective cohort study using the Veteran's Affairs Informatics and Computing Infrastructure (VINCI) database to identify patients who underwent treatment for NSCLC between 2012 and 2017 at Veteran's Health Administration Medical Centers (VHAMCs). Patients were included in the cohort if they had tumor (T) stage 1 or 2 disease, node negative (N0) disease, and underwent SABR radiation treatment based on associated Current Procedural Terminology codes. We conducted univariate and multivariate analyses for overall survival (OS) and cause-specific survival (CSS) using Cox regression models accounting for age, sex, race, histology, T stage, tobacco history, ECOG status, and VHAMC facility TV. TV was calculated as the total number of SABR treatments performed per facility over the study period and was categorized into high and low volume groups based on a median TV cutoff.Results: The observational cohort included N = 433 patients with early-stage NSCLC who underwent treatment with SABR across 25 VHAMC facilities. Most patients (83.1%) had T stage 1 disease, and nearly equal proportions had SCC (31.2%) and adenocarcinoma (32.5%) histologies, with the remaining having clinical diagnoses of NSCLC. Median facility TV was 29 SABR treatments (interquartile range 19-33). Median follow up was 657 days. Estimated 2-year overall and cause-specific survival rates were 78.4% (95% CI: 73.9% - 82.1%) and 87.0% (95% CI: 83.2% - 90.0%), respectively. On univariate analysis, high versus low facility TV was not significantly associated with OS (hazard ratio (HR) 1.08, 95% CI: 0.74-1.58) or CSS (HR 1.06, 95% CI: 0.65 - 1.73). Similarly, facility volume was not associated with OS or CSS on multivariate analysis. In a sensitivity analysis, facility volume was not associated with survival outcomes when treated as a continuous variable. Covariates associated with decreased OS included male sex (HR 4.5, P < 0.05), age over 65 (HR 1.77, P < 0.05), ECOG status 2 or greater (HR 1.94, P < 0.05), SCC histology (HR 1.66, P < 0.05), and T stage 2 disease (HR 1.68, P < 0.05).Conclusion: In this observational cohort of patients treated at VHAMCs, facility TV was not associated with survival outcomes for early-stage NSCLC radiation treatment using SABR technique. Research is ongoing to account for factors including baseline pulmonary function, comorbidities, and variations in institutional treatment patterns such as propensity for treatment with surgery versus radiation. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Patients treated with stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer (NSCLC) have high rates of local control but may be at increased risk of nodal recurrence compared to those who undergo surgical resection with more invasive nodal evaluation. The optimal treatment for patients with isolated nodal recurrence (INR) is unclear. The purpose of this study is to determine the rate of INR after SABR for early-stage NSCLC and describe patterns of care and treatment outcomes for patients that experience INR.Materials/methods: This retrospective cohort study included 342 patients with stage T1-3N0 NSCLC treated with definitive SABR. We evaluated the estimated rate of INR using the cumulative incidence function with death as a competing risk and compared baseline factors among patients who did or did not experience INR. Among patients that experienced INR, we describe patterns of treatment and outcomes including overall (OS) and progression free survival (PFS) from the time of nodal failure using the Kaplan-Meier method. OS and PFS outcomes were compared between treatment groups using the log-rank test.Results: Of the 342 patients treated with SABR from 2003-2018, 34 developed INR and 19 developed any nodal recurrence. Patients were treated with definitive SABR for T1 (62.6%, n = 214), T2 (25.4%, n = 87) and T3 (12.0%, n = 41) NSCLC with a median BED10 of 87.5. The 3- and 5-year cumulative incidence of INR was 9.3 (95% CI 6.1 - 12.4) and 10.1 (6.8 -13.4) %, respectively. Pathologic nodal staging prior to SBRT was 9.1 and 13.3 % (P = 0.68) for patients who did or did not experience INR, respectively. The median number of involved nodes at the time of recurrence was one with a maximum of four. Among the 30 patients with a known treatment course after INR, patients were treated with RT alone (26.7 %, n = 8), chemotherapy and RT (CRT) (43.3 %, n = 13), chemotherapy alone (13.3%, n = 4) or observation (16.7%, n = 5). RT regimens included standard fractionation (38.0%, n = 8), hypofractionation (52.4%, n = 11) or SABR (9.5%, n = 2). The estimated two-year OS and PFS for patients experiencing INR were 48.0 (32.6 - 70.7) % and 27.6 (14.7 - 52.8) %, respectively. Treatment with CRT was associated with improved OS (2 year est: 91.7 vs 16.7 %, P < 0.01) and PFS (2 year est: 63.9 vs 0 %, P < 0.01) over RT alone. Similarly, CRT was associated with improved OS (91.7 vs 25.0 %, P < 0.01) and PFS (63.9 vs 0%, P < 0.01) over chemotherapy alone. Median follow-up time after INR was 21.7 months.Conclusion: INR occurred in approximately 10% of patients treated for early-stage NSCLC with SABR. Treatment paradigms for post-SABR INR varied significantly at our institution and included combined chemotherapy and radiation, chemotherapy alone, SABR and hypofractionated RT. The highest rates of survival in patients with post-SABR INR were observed in those treated with combined chemotherapy and radiation. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Hemoptysis is a rare but potentially fatal toxicity associated with thoracic stereotactic ablative radiotherapy (SABR). Prior studies have suggested that vascular endothelial growth factor inhibitors (VEGFI) may potentiate the risk for pulmonary hemorrhage in patients treated with SABR for centrally located lung tumors. To what degree the risk of toxicity varies by timing of therapies or tumor location is uncertain. The purpose of this study is to evaluate the combined toxicity of VEGFIs and SABR for peripheral, central, or ultra-central tumors.Materials/methods: We evaluated patients with primary or metastatic lung tumors treated with SABR between 2008 and 2018 at a single institution. Baseline patient, tumor and treatment characteristics were evaluated. Pulmonary bleeding events were graded using CTCAE version 5.0. Rates of a grade three or higher (G3+) or any ipsilateral pulmonary hemorrhage at three years were estimated using the Kaplan-Meier method. We compared rates of bleeding by tumor location, treatment with a VEGFI, sequence of therapy and VEGFI within 90 days of SABR using the log-rank test.Results: This retrospective cohort study included a total of 925 pulmonary tumors treated with SABR in 691 patients. There were 44 patients treated with a VEGFI (bevacizumab, sorafenib, pazopanib, sunitinib or ramucirumab), with the majority receiving bevacizumab (n = 38, 86.3%). Among those treated with a VEGFI, the median interval between VEGFI therapy and SABR was 16 weeks, ranging from zero days to 3.7 years, with 15 (34.0%) patients treated within 90 days of SABR. Patients were treated with SABR to peripheral (738, 79.8%), central (137, 14.8%) and ultra-central (50, 5.4%) locations with a median BED10 of 87.5 Gy. Median follow-up was 32.2 months for the overall cohort and 46.4 months for VEGFI patients. The rate of G3+ hemorrhage was significantly higher in patients treated with a VEGFI (7.3 vs 0.8%, P < 0.01). The rate of any grade hemorrhage did not significantly vary between groups (9.4 vs 2.7%, P = 0.1). When stratified by location, both central/ultra-central tumors (21.1 vs 3.2%, P = 0.03) and peripheral tumors (3.4 vs 0.1%, P = 0.03) had increased rates of G3+ hemorrhage when treated with a VEGFI. Among patients treated with SABR and VEGFI, there was no significant difference in rates of hemorrhage when the interval was > or ≤ 90 days (12.0 vs 0.0%, P = 0.17). Similarly, there was no significant difference between rates of G3+ hemorrhage when VEGFI was given before (12.9%), after (8.3%), or before and after SABR (0.0%).Conclusion: VEGFI therapy was associated with an increased rate of high-grade hemorrhage in patients undergoing SABR to pulmonary tumors. Rates of high-grade hemorrhage were increased with VEGFI for both central/ultra-central and peripheral tumors although the absolute rate was low for peripheral tumors. While limited by low sample size and event rate, there was no correlation observed between interval or sequence of VEGFI and SABR and rate of high-grade hemorrhage. [ABSTRACT FROM AUTHOR]