Metabolic Imaging of Early Radiation-Induced Lung Injury Using Hyperpolarized 13C-Pyruvate in Rodent Lungs

Lung cancer is the leading cause of cancer related death. Radiation therapy is a prominent treatment method but leads to adverse consequences. Radiation-Induced Lung Injury (RILI) is the primary adverse consequence that limits further radiation therapy and develops in 5-37% of the treated patients. RILI proceeds in two distinct phases: a) early and reversible Radiation Pneumonitis (RP), and b) late and irreversible radiation fibrosis. Clinically, Dose Volume Histogram (DVH) parameters derived from radiation therapy planning stage are used to determine outcome and severity of RP but have been demonstrated to possess a very low predictive power. Computed Tomography (CT) is the most commonly used modality for the imaging of RP, but often only detects very late RP that leaves little room for intervention to abort the progress to irreversible radiation fibrosis. Early detection of RP using imaging may allow for interventional treatment and management of the disease and the associated symptoms in a better manner. Improvement in Dynamic Nuclear Polarization (DNP) technology has led to advancement of hyperpolarized 13-Carbon-Magnetic Resonance Imaging (13C-MRI). In this thesis, we present the investigation of early detection of RP with 13C-MRI in an animal model with the use of hyperpolarized 13C-pyruvate. A pilot study demonstrated the proof of concept along with a qualitative histological confirmation. 13C-MRI data and histology data were collected 2 weeks post irradiation of whole thorax in rodents. In the subsequent study, regional and longitudinal 13C-MRI and quantitative histology data were analyzed to demonstrate the early organ-wide response of RP. These data were collected at day 5, 10, 15 and 25 post conformal irradiation of the right rodent lung. Finally, we demonstrate a novel approach to map pH using hyperpolarized 13C-bicarbonate with the use of spiral-Iterative Decomposition of water and fat with Echo Asymmetry and Least squares estimation (IDEAL) pulse sequence. Validation of this approach by comparison to Chemical Shift Imaging (CSI) pH measurement and standard pH measurement with the aid of phantoms along with hyperpolarized 13C-bicarbonate is presented. pH mapping may play a role in the staging and therapeutic intervention of cancer

Medical Imaging Utilization Trends in Radiation Oncology over the Past Decade

Purpose/Objective(s): We quantify the increase in use of pre-treatment imaging and verification imaging in radiation oncology over the past decade. We also quantify the trend towards hypofractionation, which has partially led to increased imaging. Materials/Methods: The pre-treatment and verification imaging data used are from a single, tertiary, university-affiliated cancer center. Pre-treatment imaging was defined as magnetic resonance imaging (MRI), positron emission tomography (PET) and four-dimensional computed tomography (4DCT). Verification imaging was defined as cone-beam computed tomography (CBCT). All treatment approved plans were included from 2012 to 2021. Data extraction was performed using custom scripts interfacing with the treatment planning system (TPS) and patient information system. All registered image-sets of planning CT images with either advanced pre-treatment advanced imaging or verification images in the TPS were included. Hypofractionation sub-analysis was performed according to plans above and below 4 Gy per fraction that received a combination of pre-treatment and verification imaging. Results: Between 2012 and 2021, a total of 42,214 plans were included. In 2021, MRI, PET, and 4DCT pre-treatment imaging modalities were used for 14%, 5%, and 3% of patients, respectively, which was an increase from 5%, 2%, and 0%, in 2012. In 2021, 55% of patients received CBCT for verification imaging compared to only 2% of patients in 2012. In the sub-analysis, cohort receiving greater than or equal to 4 Gy per fraction from 2012 to 2021, the percent of patients receiving one of MRI or PET for pre-treatment imaging and CBCT guidance for verification imaging increased from 1% to 22%. For the cohort receiving less than 4 Gy per fraction, there was an increase from 2012 to 2021 of 0% to 14% of patients receiving at least one of MRI or PET pretreatment imaging and CBCT for verification imaging. Table 1: Annual use of advanced pre-treatment, verification imaging, hypofractionation, and associated combination imaging shown. Entries indicate the percent (%) of patients per year with the imaging modality used in their treatment. Conclusion: An increase in the adoption of advanced medical imaging was observed in standard of care treatments over the past 10 years. Imaging utilization continues to increase as clinical trial evidence matures. Further analysis could focus on the gap between desired standard of care for patients and the current offerings as well as the increase in capital and human resource requirement for implementation of these advancements

The Impact of Implementing Hypofractionation Prescription Regimens and Modernizing Delivery Technique on Treatment Resources in Breast Radiotherapy

Purpose/Objective(s): To determine the change in treatment resources due to the implementation of hypofractionated prescription regimen. Materials/Methods: All patients between January 1, 2012 and December 31, 2021 receiving curative intent breast radiotherapy at a tertiary cancer center were included. Plan and patient data were extracted from the patient database with the treatment planning system and direct database query. Treatment plan categorization was completed using data elements to include only curative intent. Treatment plans for seroma boost or supraclavicular irradiation were excluded to ensure this analysis did not double-count regional nodal irradiation contribution or confound boost with hypofractionation. Treatment delivery time is recorded in the database for each patient treatment delivered. Average patient treatment time per year was estimated by multiplying the average fractions each year by average time in the same year. The standard fractionation regimens (95% of patients) are 42.56 Gy in 16, 40 Gy in 16, 27 Gy in 5 (accelerated partial breast irradiation), and 26 Gy in 5 (FAST-Forward). In the analysis, implementation milestones are indicated for new prescription regimens and delivery technique changes including deep inspiration breath hold (DIBH) for left-sided patient treatments and daily verification imaging. Results: A total of 6505 patients were included. Table 1 details the total number of patients per year, the average number of fractions treated per patient, and the average treatment time of each patient plan. The average total fractions per treatment decreased from 17.5 in 2012 to 10.9 in 2021. The average treatment delivery time increased from 12.9 minutes to 21.4 minutes. Conclusion: In considering total treatment resources, the interplay between hypofractionation and modernization delivery techniques is complex. The impact of hypofractionation reduced the average number of fractions but total treatment resources are offset with the implementation of modern treatment delivery techniques. Hypofractionated prescription regimens reduce the time and travel commitment required of patients on an individual basis, contributing to person-centered care