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Left-sided breast cancer patients receiving adjuvant radiotherapy are at risk for coronary artery disease, and/or radiation mediated effects on the microvasculature. Previously our laboratory demonstrated in canines with hybrid .sup.18 FDG/PET a progressive global inflammatory response during the initial one year following treatment. In this study, the objective is to evaluate corresponding changes in perfusion, in the same cohort, where resting myocardial blood flow (MBF) was quantitatively measured. In five canines, Ammonia PET (.sup.13 NH.sub.3) derived MBF was measured at baseline, 1-week, 1, 3, 6 and 12-months after cardiac external beam irradiation. MBF measurements were correlated with concurrent .sup.18 FDG uptake. Simultaneously MBF was measured using the dual bolus MRI method. MBF was significantly increased at all time points, in comparison to baseline, except at 3-months. This was seen globally throughout the entire myocardium independent of the coronary artery territories. MBF showed a modest significant correlation with .sup.18 FDG activity for the entire myocardium (r = 0.51, p = 0.005) including the LAD (r = 0.49, p = 0.008) and LCX (r = 0.47, p = 0.013) coronary artery territories. In this canine model of radiotherapy for left-sided breast cancer, resting MBF increases as early as 1-week and persists for up to one year except at 3-months. This pattern is similar to that of .sup.18 FDG uptake. A possible interpretation is that the increase in resting MBF is a response to myocardial inflammation.

Purpose For lung and liver tumors requiring radiotherapy, motion artifacts are common in 4D‐CT images due to the small axial field‐of‐view (aFOV) of conventional CT scanners. This may negatively impact contouring and dose calculation accuracy and could lead to a geographic miss during treatment. Recent advancements in volumetric CT (vCT) enable an aFOV up to 160 mm in a single rotation, which may reduce motion artifacts. However, the impact of large aFOV on CT number required for dose calculation needs to be evaluated before clinical implementation. The objective of this study was to determine the utility of a 256‐slice vCT scanner for 4D‐CT simulation by evaluating image quality and generating relative electron density (RED) curves. Methods Images were acquired on a 256‐slice GE Revolution CT scanner with 40 mm, 80 mm, 120 mm, 140 mm, and 160 mm aFOV. Image quality was assessed by evaluating CT number linearity, uniformity, noise, and low‐contrast resolution. The relationship between each quality metric and aFOV was assessed. Results CT number linearity, uniformity, noise, and low‐contrast resolution were within the expected range for each image set, except CT number in Teflon and Delrin, which were underestimated. Spearman correlation coefficient (ρ) showed that the CT number for Teflon (ρ = 1.0, p = 0.02), Delrin (ρ = 1.0, p = 0.02), and air (ρ = 1.0, p = 0.02) was significantly related to aFOV, while all other measurements were not. The measured deviations from expected values were not clinically significant. Conclusion These results suggest that vCT can be used for CT simulation for radiation treatment planning.

Radiation may unintentionally injure myocardial tissue, potentially leading to radiation-induced cardiac disease (RICD), with the net benefit of non-small cell lung cancer (NSCLC) radiotherapy (RT) due to the proximity of the lung and heart. RTOG-0617 showed a greater reduction in overall survival (OS) comparing higher doses to standard radiation doses in NSCLC RT. V Heart has been reported as an OS predictor in the first- and fifth-year follow-ups. A worsening OS trend was reported in another study where the mean left ventricle dose (mean LV) was ≥14.5 Gy. It is therefore important to spare the heart, specifically the LV, from radiation. Furthermore, dose-limiting factors toward the normal lung should be accounted for to prevent radiation-induced lung injury. The LV and left anterior descending artery (LAD) were also contoured on the average four-dimensional computed tomography (4D-CT) dataset that contained clinically defined targets and normal structures for stage III NSCLC RT. The prescribed treatment plans (n=15) were retrospectively optimized with the clinical goals of minimizing the mean LV and mean heart dose while maintaining the dose constraint of V Lung ≤30% and V PTV ≥95%. Dose-volume histograms were used to compare the heart and lung dosimetric parameters between the delivered and reoptimized RT plans. A significant reduction (p≤0.044) was observed in the mean LV, mean heart dose, mean LAD dose, max LAD dose, and V Heart from the reoptimized RT plans. V Lung ≤30% and V PTV ≥95% were maintained, and no differences were observed in the mean lung, V Lung, V Lung, mean esophagus, and max cord. Minimizing the LV dose in NSCLC RT plans is achievable and dosimetrically advantageous for the heart while maintaining dose constraints to the normal lung and maximizing tumor control. Radiation dose reduction to cardiac substructures may decrease the RICD risk in NSCLC patients.

Adjuvant whole-breast radiotherapy (RT) is a significant part of the standard of care treatment after breast cancer (BC) conserving surgery. Modern techniques including intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) have constituted to better target coverage and critical organs sparing. However, BC survivors are at risk of developing radiation-induced cardiac toxicity. Hence, deep-inspiration breath-hold (DIBH) techniques have been implemented at many centers to further reduce cardiac exposure but require compliance. 4D-CT robust optimization can account for heart intrafractional motion per breathing phase. The optimization has been explored in cardiac sparing of breast IMRT compared to DIBH in a small sample size but has not been evaluated in substructures sparing, nor in VMAT. To provide patients who are not compliant to breath-hold with an optimal treatment approach, various heart sparing techniques need to be evaluated for statistical significance and clinical feasibility. This retrospective study aimed to provide an extensive dosimetric heart sparing comparison of free-breathing, 4D-CT-based treatment planning, including robust optimization with DIBH-based treatment planning. Combinations of forward and inverse IMRT and VMAT are also considered. Fifteen early stage left-sided BC standard treatment plans were selected. Breast, lung, left anterior descending artery (LAD), left ventricle (LV), and the whole heart were contoured on each 4D-CT phase and DIBH CT dataset. Each treatment plan was optimized using forward/inverse IMRT and VMAT on the following CT datasets: DIBH, average 4D-CT, and the complete 4D-CT dataset needed for robust optimization. Dose-volume histograms were used to compare V Heart, mean heart dose, mean and max LAD dose, mean LV dose, and V Lung. All RT techniques assessed including 4D robust optimization were clinically feasible. Statistically significant differences in mean heart, LAD and LV dose, max LAD dose, and V Heart (p < 0.01) but no difference in V Lung (p = 0.29) were found between different techniques. IMRT DIBH achieved the optimal cardiac and substructure sparing among treatment plans. 4D robust IMRT had significantly greater mean heart and LV dose than DIBH IMRT (p ≤ 0.01), except LAD dose. Among free-breathing methods, no difference in all cardiac and substructure dose parameters was observed (p > 0.2) in comparing forward and inverse IMRT with average 4D-CT, inverse average 4D-CT, and 4D robust with IMRT, and between average 4D-CT VMAT and 4D robust VMAT. Only V Heart and mean LV dose were significantly greater in 4D robust VMAT (p < 0.01) compared to DIBH VMAT. Mean heart and LV doses were significantly reduced (p < 0.01) in DIBH IMRT compared to DIBH VMAT. Moreover, mean heart and LV dose, V Heart were significantly reduced in inverse IMRT average 4D-CT compared to average 4D-CT VMAT (p < 0.02) and in 4D robust IMRT compared to 4D robust VMAT (p < 0.04). This study demonstrated the clinical feasibility of 4D robust optimization in limiting the cardiac and substructures dose during free-breathing RT with both IMRT/VMAT for patients who are not compliant with breath-hold RT. However, this study also presents that 4D robust optimization can reduce LAD dose but not fully outperform DIBH or conventional 4D-CT-based planning with IMRT/VMAT in heart sparing in treating early staged left-sided BC patients.

Inflammatory bowel disease (IBD) is a relative contraindication to external beam radiation therapy (EBRT) for prostate cancer patients due to fear of increased risk of gastrointestinal (GI) toxicity. High-dose-rate (HDR) brachytherapy, capable of minimizing radiation dose to surrounding tissues, is a feasible alternative. Given limited data, this study examined the safety profile of HDR brachytherapy in this setting. We conducted a retrospective review of patients with localized prostate cancer and IBD treated with HDR brachytherapy at the University of California San Francisco (UCSF), between 2010 and 2022. Eligibility criteria included biopsy-proven prostate cancer, no distant metastases, absence of prior pelvic radiotherapy, IBD diagnosis, and at least one follow-up visit post-treatment. Eleven patients were included, with a median follow-up of 28.7 months. The median dose administered was 2700 cGy (range, 1500-3150 cGy) over 2 fractions (range, 1-3 fractions). Two patients also received EBRT. Rectal spacers (SpaceOAR) were applied in seven patients. All patients experienced acute genitourinary (GU) toxicity, ten of which were grade 1 and one was grade 2. Eight patients experienced late grade 1 GU toxicity, and three patients had late grade 2 GU toxicity. GI toxicities were similarly low-grade, with six grade 1 acute toxicity, no grade 2 or higher acute toxicity, six grade 1 late toxicity, and one late grade 2 GI toxicity. No grade 3 or higher acute or late GI or GU toxicities were reported. HDR brachytherapy appears to be a safe and tolerable treatment modality for patients with prostate cancer and IBD, with minimal acute and late GI and GU toxicity. These findings warrant multi-institutional validation due to small sample size.

Brain metastases are a frequent and debilitating manifestation of advanced cancer. Here, we collect and analyze neuroimaging of 3,065 cancer patients with 13,067 brain metastases, representing an extensive collection for research. We find that metastases predominantly localize to high perfusion areas near the grey-white matter junction, but also identify notable differences depending on the primary cancer histology as well as brain regions which do not conform to this relationship. Lung and breast cancers, in contrast to melanoma, frequently metastasize to the cerebellum, hinting at biological pathways of spread. Additionally, the deep brain structures are relatively spared from metastasis, regardless of primary cancer type. Leveraging this data, we propose a probabilistic brain metastasis risk model to enhance the therapeutic ratio of whole-brain radiotherapy by targeting high risk areas while preserving cortical and subcortical brain regions of functional significance and low metastasis risk, potentially reducing the cognitive side effects of therapy. In patients with advanced cancer, the development of brain metastasis (BM) often signals a worsening prognosis with limited therapeutic options. Here, the authors assemble a large, open-source neuroimaging dataset of BM and perform spatial and morphological analysis which they use to develop a framework for function-sparing brain radiotherapy design.

External beam radiation treatment is often included in standard breast cancer and nonsmall cell lung cancer patients’ curative management. With the advances in radiation treatment (RT) techniques, such as the development of intensity-modulated radiation therapy and volumetric modulated arc therapy, local and regional control benefits are established. However, both cancer type survivors are prone to develop radiation-induced cardiac disease in their cured life. Furthermore, our laboratory previously demonstrated an inflammatory response in canine models using 18FDG/PET imaging during the initial year following RT.Hence, the overall goal of this thesis is to assess early functional changes and inflammation response in the heart after irradiation in both animal and patient pilot studies with the use of multi-modality imaging. Additionally, planning studies were undertaken to investigate the potential of reducing dose to the heart and substructure, including the left ventricle and the left anterior descending artery, which are unintentionally subjected to a higher dose during RT. Various RT planning techniques including deep-inspiration breath-hold and 4D Robust optimization, which can be applied to treat breast cancer are also examined. This is aimed to provide clinically feasible alternative options for patients who are non-compliant to breath-hold, without compromising target coverage.In this thesis, we established a clinically feasible protocol to assess early cardiac functional changes and inflammation response of current radiation treatment techniques that are dedicated to minimizing cardiac dose and radiation-induced cardiac toxicity. This included multi-modality cardiac imaging assessment using hybrid PET/MR and CT perfusion imaging with serial blood work performed. Additionally, from the extensive dosimetric heart sparing treatment planning study, we were able to demonstrate/present clinical feasible free-breathing options for patients who are non-compliant with breath-hold treatment. In the future, the benefits of cardiac dose mitigation strategies can be evaluated with the use of multi-modality imaging techniques.

BackgroundLeft-sided breast cancer patients receiving adjuvant radiotherapy are at risk for coronary artery disease, and/or radiation mediated effects on the microvasculature. Previously our laboratory demonstrated in canines with hybrid 18FDG/PET a progressive global inflammatory response during the initial one year following treatment. In this study, the objective is to evaluate corresponding changes in perfusion, in the same cohort, where resting myocardial blood flow (MBF) was quantitatively measured.MethodIn five canines, Ammonia PET (13NH3) derived MBF was measured at baseline, 1-week, 1, 3, 6 and 12-months after cardiac external beam irradiation. MBF measurements were correlated with concurrent 18FDG uptake. Simultaneously MBF was measured using the dual bolus MRI method.ResultsMBF was significantly increased at all time points, in comparison to baseline, except at 3-months. This was seen globally throughout the entire myocardium independent of the coronary artery territories. MBF showed a modest significant correlation with 18FDG activity for the entire myocardium (r = 0.51, p = 0.005) including the LAD (r = 0.49, p = 0.008) and LCX (r = 0.47, p = 0.013) coronary artery territories.ConclusionIn this canine model of radiotherapy for left-sided breast cancer, resting MBF increases as early as 1-week and persists for up to one year except at 3-months. This pattern is similar to that of 18FDG uptake. A possible interpretation is that the increase in resting MBF is a response to myocardial inflammation.