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Biology-guided radiotherapy utilizes direct photon emissions from a positron emission tomography (PET)-avid tumor to direct planned prescription dose to the tumor. The purpose of this work is to characterize the tracked dose delivery and dosimetric performance of BgRT as a function of changes in tumor location during treatment, while contrast of tumor radioactivity relative to the background concentration is kept constant. A medical technology X1 system was utilized to create a conformal plan and deliver 1000 cGy dose in a single fraction. The experimental setup consisted of a cylindrical volumetric assembly (phantom) encapsulating a 22 mm ball target structure and a d avoidance structure. These structures were filled with F-18 fluorodeoxyglucose (FDG) and water solution with an activity concentration of 56.99 kBq/ml while the background was filled with 6.84 kBq/ml, providing a target-to-background ratio (TBR) of 8.18:1. Ashland EBT-XD monochromatic x-ray film was used as a primary diagnostic tool to characterize the tracked dose delivery and dosimetric performance of the system. A 5 cm by 10 cm piece of x-ray film was placed in between the two hemispheres of the 22 mm ball target. The patient-specific quality assurance (PSQA) is a helical assembly of 1,386 semiconductor diodes, widely used for quality assurance of radiation therapy plans. It measures the dose delivered by linear accelerator and compares it with the planned dose. The activity filled phantom was sealed and loaded in the patient-specific quality assurance (PSQA). Before proceeding to a 10 mm linear shift i n the +IEC y-axis was applied to the 22 mm ball target with respect to the to simulate a sudden patient shift. After treatment completion the x-ray film was analyzed using green channel to obtain estimation of 3%/3 mm absolute dose gamma within the planning treatment volume (PTV) and dose profiles. The irradiated x-ray film demonstrated 3%/3 mm gamma within the PTV of 95.08%. X-ray film analysis demonstrated that the delivered dose closely followed the 10 mm linear shift in the +IEC y-axis, and good dosimetric agreement was achieved between planned and delivered dose within the target. [ABSTRACT FROM AUTHOR]

This work discusses delivery accuracy metrics for target point-of-view films used to evaluate BgRT. BgRT is a tracked delivery methodology that relies on the use of a positron emission tomography (PET) radiopharmaceutical to track and deliver the prescription dose. Intended for one or multiple PET avid targets with asynchronous non-bulk motion, delivery metrics must quantify target coverage and plan accuracy. For BgRT, we evaluated 3%/3mm gamma index inside the PTV against a novel iso-dose line to PTV "margin" metric for spatial analysis. Two studies were performed as a proof of principle demonstration of margin importance. In our first study, a large torso phantom was prepared with an FDG fillable 22 mm ball target and a c-shaped avoidance structure. A 10 Gy/fraction plan was created on a medical technology company system using a planning PET image with target-to-background ratio (TBR) of 8.34:1. Contouring for the plan used a 22 mm GTV and a 32 mm PTV. The treatment used a TBR of 8.12:1 with target and background concentration of 70.07 kBq/ml and 8.63 kBq/ml, respectively. In our second study using the same phantom, a 10 Gy/fraction plan using a 26 mm target was prepared with a planning PET image with a TBR of 12.4:1. Contours for the plan used a 26 mm GTV and a 36 mm PTV. The treatment used a TBR of 12:47:1 with target and background concentration of 75.82 kBq/ml and 6.08 kBq/ml, respectively. However, the delivery was performed to a 22 mm target to model a biodistribution change. The PTV in the plan was not changed. Variable 3D sinusoidal target motion was used for all planning and treatment studies; study 1 and 2 used max amplitudes of 16 mm and 13 mm, respectively. To use the "margin" metric, both plans had ~95% PTV coverage with a conformity index (CI) of 1.03. All studies used Ashland EBT-XD film cut to approximately 10 x 10 cm2 to measure delivered dose. Analysis of the films included the calculation of the 3%/3mm gamma criterion within the PTV. Margin loss was calculated as the maximum spatial contraction from the PTV to the film recorded 97% of prescription dose iso-dose line. Acceptable margin loss was limited to 3 mm, a criterion created by the PET signal spatial uncertainty from motion. The irradiated film from study 1 demonstrated 0 mm of margin loss with respect to the PTV. Film 3%/3mm gamma within the PTV was 97.33%. Film from study 2 demonstrated 0 mm of margin loss but a PTV 3%/3mm gamma of 75.33%. In study 1, both the margin metric and PTV gamma produced favorable results. In study 2, PTV gamma failed, but the margin metric passed. The margin metric accounted for the biodistribution change from the 26 mm to 22 mm target, indicating coverage was maintained during treatment. As no dosimetry metric is currently established for tracked delivery, a margin metric may be a more appropriate measure of target coverage than the conventional 3%/3mm measurement. [ABSTRACT FROM AUTHOR]

Our study aims to identify patient subgroups with metastatic oropharynx cancers who may derive the most benefit from escalated therapy, using demographics, disease characteristics, and treatment patterns. The National Cancer Database (NCDB) was queried for patients diagnosed with metastatic squamous oropharynx cancers between 2004 and 2019. Variables including age, gender, race, Charlson-Deyo comorbidity index (CCI), high-risk human papillomavirus (HPV) status, location of metastases, number of metastatic sites, and type of treatment received were evaluated. Patients with unknown HPV status or missing data were removed from analysis. Descriptive statistics were generated and both univariate and multivariate analyses (Cox regression) for median overall survival (OS) were performed. Utilizing the classification and regression tree (CART) algorithm, we developed a decision tree model based on the multivariate analysis results to examine pathways to survival based on HPV status, with a 70-30 training-test split. For post-model development, we calculated the median survival time at parent nodes within the decision tree. After excluding cases with missing data, 1564 remained, with 1349 being male (86.3%) and 1306 being white (83.5%). 1176 (75.2%) had a CCI of 0 and 897 (57.4%) were HPV-positive (HPV-P). Lung metastases were seen in 761 (48.7%) followed by involvement of distant lymph nodes (468, 29.9%), and bone (455, 29.1%). 1068 (68.3%) had a single site of metastasis. 191 (12.2%) received no therapy, 316 (20.2%) received systemic treatment alone, 155 (9.9%) received local treatment alone, and 827 (52.9%) received combined systemic and local treatments (Combo). HPV-P patients who received Combo had an OS of 27.7 months. In the multivariate models, HPV status, CCI, tumor size, time to initiation of treatment, number of metastatic sites, and treatment type were significant predictors of survival. The decision tree nodes with the greatest impact on survival were HPV status, treatment type, and number of metastatic sites. Patients who were HPV-P, received Combo, had one metastatic site of disease, and had involvement of distant lymph nodes had a median OS of 53.7 months. HPV-P patients with non-distant lymph node single site disease who received Combo had a median OS of 28.0 months. The remainder of patient nodes had median OS under 14 months. Significant survival differences are observed among metastatic oropharynx cancer patients, with HPV status, metastatic burden, and treatment type playing crucial roles. Aggressive combined modality treatment could greatly benefit certain HPV-positive patient subgroups. Utilizing decision tree methodology facilitated the creation of an interpretable model for outcome prediction, enabling personalized clinical decision-making for our study population. [ABSTRACT FROM AUTHOR]

Oligometastatic disease is an intermediate state between locoregional disease and widely metastatic disease. Previous work by our group showed a significant difference between the median survival of uterine cancer patients with a single metastatic site versus multiple sites, hence we defined our oligometastatic cohort as having one metastatic site at diagnosis. The aim of our current analysis was to explore the variables associated with stereotactic body radiotherapy (SBRT) use in this oligometastatic population and whether there are implications for survival. The National Cancer Database was analyzed in patients diagnosed with uterine cancer between 2004-2019. We excluded patients with non-metastatic disease at diagnosis, lack of metastatic sites listed, multiple primaries, sarcoma and neuroendocrine histologies, and missing survival data. We included patients treated with radiotherapy and defined SBRT as ≤5 fractions and ≥500cGy dose per fraction. Univariable and multivariable logistic regression analyses were performed to assess the association of SBRT with covariates. Propensity score matching was then performed to match a cohort with patients treated with SBRT in a 1:3 ratio based on age, race/ethnicity, Charles-Deyo comorbidity index, grade, treatment and metastatic site. Survival analyses were performed using Kaplan-Meier analysis and log-rank tests. Among 641,276 women with uterine cancer, 13,974 remained after exclusion and 9,914 had oligometastatic disease with involvement of one metastatic site. In this population, 2,303 (23.2%) patients underwent radiotherapy and 70 (0.7%) were treated with SBRT. Univariable analysis identified the following variables to be significantly associated with SBRT: age, grade, housing, race/ethnicity, year of diagnosis and metastatic site. Upon multivariable analysis, the following variables remained significant: age (OR: 0.979; 95% CI = 0.956-1.00, p = 8.62e-2); race: Black (OR: 0.271; 95% CI = 7.80e-2-0.712; p = 1.77e-2); year of diagnosis (OR: 1.39; 95% CI = 1.22-1.60; p = 1.76e-6); and metastatic site: bone (OR: 7.84 95% CI = 2.18-50.3; p = 6.78e-3), brain (OR: 53.5; 95% CI = 14.8-345; p = 1.85e-7). Survival analysis of oligometastatic patients treated and underwent propensity score matching showed a median overall survival of 24.6 months (95% CI = 16.5-NA) in the SBRT cohort versus 14.5 months (95% CI = 11.9-22) in the non-SBRT cohort (p = 0.055). SBRT use in oligometastatic uterine cancer was found to be increased in younger patients, metastatic sites involving bone or brain, and later years and was decreased in Black women. These results underscore potential missed opportunities for utilizing ablative techniques that may have implications for increasing overall survival in oligometastatic uterine cancer as suggested by our survival analysis. [ABSTRACT FROM AUTHOR]

Enhanced cone beam computed tomography (eCBCT) is a novel imaging modality offering improved image quality and monitoring of tumor and normal tissue changes during radiation therapy (RT), holding the potential to revolutionize adaptive RT approaches. A critical step toward application in these domains is the assessment of eCBCT performance in accurately segmenting normal tissues and tumor volumes. Consequently, our study is designed to assess eCBCT's efficacy in precise segmentation of normal tissues and tumor volumes by comparing observer agreement and accuracy against traditional CT simulations (CTsims) in a head and neck cancer (HNC) patient cohort. We acquired paired CTsims and first fraction eCBCT images for five patients undergoing definitive RT for HNC. Regions of interest (ROIs) for primary tumors and organs at risk (OARs) were manually segmented on both modalities by a primary observer, without additional imaging information, to prevent bias. Seventeen ROIs were delineated per image. Four independent observers (two experts and two residents) also segmented eCBCTs. Paired CTsim/eCBCT were co-registered for each patient and ROIs were propagated to the CTsim for comparison. Agreement of eCBCT segmentation volumes to CTsim volumes were calculated using volume overlap and surface distance metrics. Mann-Whitney U test was used to compare the performance between different ROI types and the Intraclass Correlation Coefficient (ICC) was used to calculate the inter-observer variability. Across all patients, 425 ROIs were segmented. Dice similarity coefficients (DSC) had a median and interquartile range of 0.8 (0.7-0.83), mean surface distance (MSD) was 1.5 mm (1.1-2.3), and the maximum Hausdorff distance (Max HD) was 9.3 mm (6.4-13.7). Mandibular bone ROIs achieved the best volume overlap performance (average DSC 0.88) and minimal MSD (average 0.89 mm), with muscles of mastication also performing well (average DSC 0.82 and MSD 1.18 mm). Salivary glands displayed commendable results (average DSC 0.77 and MSD 2 mm). However, GTV ROIs had the worst performance with an average DSC of 0.5 and MSD of 4 mm. GTV ROIs had statistically significant lower DSC, and higher MSC and Max HD compared to all other OARs (P <0.001). The ICC showed excellent inter-observer agreement for both DSC and Max HD metrics of 0.93 (95% CI= 0.9-0.95) and 0.97 (95% CI = 0.96-0.98), respectively, for normal tissue ROIs as well as a good agreement of 0.87 (95% CI = 0.74-0.94) for MSD. On the contrary, ICC showed poor inter-observer agreement for GTV ROIs using DSC 0.5 (95% CI = -0.8-0.9) and moderate agreement 0f 0.71 (95% CI = -0.07-0.97) using MSD. This pilot study reveals that manual segmentation of eCBCT in HNC patients undergoing RT aligns closely with CTsim for most OARs, maintaining high observer agreement. However, GTV segmentation using eCBCT alone, without contrast or diagnostic imaging integration, is unreliable. [ABSTRACT FROM AUTHOR]