Objective: This work aims to develop an automated segmentation method for the prostate and its surrounding organs-at-risk (OAR) in pelvic computed tomography to facilitate prostate radiation treatment planning. Approach: In this work, we propose a novel deep-learning algorithm combining a U-shaped convolutional neural network (CNN) and vision transformer (VIT) for multi-organ (i.e., bladder, prostate, rectum, left and right femoral heads) segmentation in male pelvic CT images. The U-shaped model consists of three components: a CNN-based encoder for local feature extraction, a token-based VIT for capturing global dependencies from the CNN features, and a CNN-based decoder for predicting the segmentation out- come from the VIT’s output. The novelty of our network is a token-based multi-head self-attention (MHSA) mechanism used in the transformer, which encourages long- range dependencies and forwards informative high-resolution feature maps from the encoder to the decoder. In addition, a knowledge distillation strategy is deployed to further enhance the learning capability of the proposed network. Main results: We evaluated the network using: 1) a dataset collected from 94 patients with prostate cancer; 2) and a public dataset CT-ORG. A quantitative evaluation of the proposed network’s performance was performed on each organ based on 1) volume similarity between the segmented contours and ground truth using Dice score, segmentation sensitivity, and precision, 2) surface similarity evaluated by Hausdorff distance (HD), mean surface distance (MSD) and residual mean square distance (RMS), 3) and percentage volume difference (PVD). The performance was then compared against other state-of-art methods. Average volume similarity measures obtained by the network over all organs were Dice score = 0.91, sensitivity = 0.90, precision=0.92, average surface similarities were HD = 3.78 mm, MSD = 1.24 mm, RMS = 2.03 mm; average percentage volume difference was PVD = 9.9% on the first dataset. The network also obtained Dice score = 0.93, sensitivity = 0.93, precision=0.93, average surface similarities were HD = 5.82 mm, MSD = 1.16 mm, RMS = 1.24 mm; average percentage volume difference was PVD = 6.6% on the CT-ORG dataset. Significance: In summary, we propose a token-based transformer network with knowledge distillation for multi-organ segmentation using CT images. This method provides accurate and reliable segmentation results for each organ using CT imaging, facilitating the prostate radiation clinical workflow.

Purpose/Objectives: The immuno-inflammatory state has been shown to be associated with poor outcomes following radiation therapy (RT). We conducted an a priori designed validation study using serum specimens from RTOG 0521. It was hypothesized the pre-treatment inflammatory state would correlate with clinical outcomes. Materials/Methods: Patients on RTOG 0521 had serum banked for biomarker validation. This study was designed to validate previous findings showing an association between elevations in C-Reactive Protein (CRP) and shorter biochemical disease free survival (bDFS). CRP levels were measured in pre-treatment samples. An exploratory panel of related cytokines were also measured including: monocyte chemotactic protein-1 (MCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17A, IL-23, and tumor necrosis factor (TNFα). The primary endpoint examined was bDFS. Additional exploratory endpoints included overall survival, distant metastases, and toxicity events attributed to RT. Results: 202 patients in RTOG/NRG 0521 had serum samples available. Median age was 66 years (48–83), 90% of patients were white. There was not an association between high sensitivity (hsCRP) and bDFS (adjusted hazard ratio [HR]=1.07 per one log increase in CRP, 95% CI: 0.83 – 1.38, p=0.60). In the exploratory, unplanned analysis, pre-treatment IL-10 was significantly associated with worse bDFS (adjusted HR=1.61 per log increase, p=0.0027) and distant metastases (HR=1.55 per log increase, p=0.028). The association of IL-10 with bDFS was maintained on a multiplicity adjustment. The exploratory analysis of pretreatment levels of IFN-γ, IL-1b, IL-2, IL-13, IL-23 were negatively associated with g 2 or higher pollakiuria (adjusted OR=0.64, 0.65, 0.71, 0.72, and 0.74, respectively, all p<0.05) and IL-6 was negatively associated with g 2 or higher ED (OR=0.62, p=0.027). Conclusions: Pretreatment CRP is not associated with a poorer bDFS following RT. In a hypothesis generating analysis, higher baseline levels of IL-10 were associated with lower rates of bDFS. These findings require additional prospective evaluation.

In this work, we demonstrate a method for rapid synthesis of high-quality CT images from unpaired, low-quality CBCT images, permitting CBCT-based adaptive radiotherapy. We adapt contrastive unpaired translation (CUT) to be used with medical images and evaluate the results on an institutional pelvic CT dataset. We compare the method against cycleGAN using mean absolute error, structural similarity index, root mean squared error, and Frèchet Inception Distance and show that CUT significantly outperforms cycleGAN while requiring less time and fewer resources. The investigated method improves the feasibility of online adaptive radiotherapy over the present state-of-the-art.

Importance: Very high-risk (VHR) prostate cancer is an aggressive substratum of high-risk prostate cancer, characterized by high prostate-specific antigen levels, high Gleason score, and/or advanced T category. Contemporary management paradigms involve advanced molecular imaging and multimodal treatment with intensified prostate-directed or systemic treatment-resources more readily available at high-volume centers. Objective: To examine radiation facility case volume and overall survival (OS) in men with VHR prostate cancer. Design, Setting, and Participants: A retrospective cohort study was performed from November 11, 2022, to March 4, 2023, analyzing data from US facilities reporting to the National Cancer Database. Patients included men diagnosed with nonmetastatic VHR prostate cancer by National Comprehensive Cancer Network criteria (clinical T3b-T4 category, primary Gleason pattern 5, >4 cores with grade group 4-5, and/or 2-3 high-risk features) and treated with curative-intent radiotherapy and androgen deprivation therapy between January 1, 2004, to December 31, 2016. Exposures: Treatment at high- vs low-average cumulative facility volume (ACFV), defined as the total number of prostate radiotherapy cases at an individual patient's treatment facility from 2004 until the year of their diagnosis. The nonlinear association between a continuous ACFV and OS was examined through a Martingale residual plot; an optimal ACFV cutoff was identified that maximized the separation between high vs low ACFV via a bias-adjusted log rank test. Main Outcomes and Measures: Overall survival was assessed between high vs low ACFV using Kaplan-Meier analysis with and without inverse probability score weighted adjustment and multivariable Cox proportional hazards. Results: A total of 25 219 men (median age, 71 [IQR, 64-76] years; 78.7% White) with VHR prostate cancer were identified, 6438 (25.5%) of whom were treated at high ACFV facilities. Median follow-up was 57.4 (95% CI, 56.7-58.1) months. Median OS for patients treated at high ACFV centers was 123.4 (95% CI, 116.6-127.4) months vs 109.0 (95% CI, 106.5-111.2) months at low ACFV centers (P < .001). On multivariable analysis, treatment at a high ACFV center was associated with lower risk of death (hazard ratio, 0.89; 95% CI, 0.84-0.95; P < .001). These results were also significant after inverse probability score weighted-based adjustment. Conclusions and Relevance: In this cohort study of patients with VHR prostate cancer who underwent definitive radiotherapy and androgen deprivation therapy, facility case volume was independently associated with longer OS. Further studies are needed to identify which factors unique to high-volume centers may be responsible for this benefit.

Background: Chemotherapy is the backbone of many cancer therapies; however, the terminology used to describe chemotherapy may be difficult for patients to understand, particularly in underserved populations. Studies have shown that educational videos can improve patient understanding of cancer-related terms. The goal of this study was to identify chemotherapy terms that were difficult for an underserved population to understand and then develop and test educational videos describing these terms. Methods: A word bank of 50 difficult-to-understand chemotherapy terms was developed by querying 15 providers and 50 patients at an underserved hospital. Twenty of these terms were then tested with 50 additional patients to determine rates of misunderstanding. Six pilot educational videos describing 6 important terms were created using VideoScribe and then assessed with 50 patients to see if they improved understanding. Results: Fifteen of the 20 terms tested to establish rates of misunderstanding were misunderstood by more than one third of patients, with 98% unable to define maintenance, 74% unable to define cancer, and 58% unable to define chemotherapy. Patient understanding of all 6 terms improved by at least 20% after watching the videos. Notable improvement was reported for palliative chemotherapy, where before-and-after video understanding increased from 0% to 72%. Conclusion: Chemotherapy, a backbone of cancer treatment, is described with terms that are difficult to understand. Short, animated educational videos can significantly increase patient understanding of chemotherapy terminology.

Purpose: The aim of this study is to examine the reproducibility of anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (anti-3-[18F]FACBC) quantitative measurements in key background structures and untreated malignant lesions. Procedures: Retrospective review of 14 patients who underwent follow-up anti-3-[18F]FACBC positron emission tomography-X-ray computed tomography (PET-CT) for prostate carcinoma recurrence. Standard uptake values (SUV) were measured in both original and follow-up scans in key background structures and untreated malignant lesions. Absolute and percent mean difference in SUV between scans and interclass correlation coefficients (ICC) were also computed. Results: Mean (±SD, range) scan interval was 17.4 months (±7.1, 4–29). %Mean difference in SUVmean was <20 % in background structures with low absolute differences. ICCs were >0.6 except for early-phase blood pool (ICC=0.4). SUVmax in malignant lesions without interim therapy increased or remained stable over time. Conclusions: Despite variable time interval between scans, FACBC PET-CT demonstrates acceptable reproducibility in key background structures. Untreated malignant lesions showed stable or increased uptake over time. A formal test-retest study is planned.

Purpose We explored the influence of FACBC (fluciclovine) PET/CT on the decision to offer radiotherapy and radiotherapy treatment field recommendations in postprostatectomy patients with recurrent prostate cancer. Patients and Methods After obtaining institutional review board approval and informed consent, 87 patients with detectable prostate-specific antigen (PSA) levels were recruited into a prospective clinical trial. After an initial provider-determined radiotherapy plan based on conventional imaging, 44 of 87 patients were randomized to additionally undergo fluciclovine PET/CT. Pre- and post-fluciclovine radiotherapy decisions were compared and changes were noted. Statistical significance of these decision changes was determined. Results Two of 44 patients in the experimental arm dropped out before fluciclovine scanning. Thirty-four (81.0%) of 42 had positive results on fluciclovine. Overall radiotherapy decision was changed in 17 (40.5%) of 42. Mean PSA, original Gleason score, and prostatectomy-PET interval did not differ significantly between patients with and without radiotherapy decision changes. Two (4.8%) of 42 had the decision for radiotherapy withdrawn due to positive extrapelvic findings. Radiotherapy field decision was changed in 15 (35.7%) of 42. Eleven (73.3%) of 15 had fields changed from prostate bed only to both prostate bed and pelvis, while 4 (26.7%) of 15 had fields changed from both prostate bed and pelvis to prostate bed only. Changes in overall radiotherapy decision and field were statistically significant (P < 0.0001). However, the change in the decision to offer radiotherapy or not was not statistically significant (P = 0.15). Conclusions Fluciclovine PET/CT significantly changed radiotherapy management decisions in postprostatectomy patients with recurrent prostate cancer. Further work in determining differences in PSA-free survival is ongoing.

Deformable (non-rigid) registration is an essential tool in both adaptive radiation therapy and image-guided radiation therapy to account for soft-tissue changes during the course of treatment. The evaluation method most commonly used to assess the accuracy of deformable image registration is qualitative human evaluation. Here, we propose a method for systematically measuring the accuracy of an algorithm in recovering artificially introduced deformations in cases of rigid geometry, and we use that method to quantify the ability of a modified basis spline (B-Spline) registration algorithm to recover artificially introduced deformations. The evaluation method is entirely computer-driven and eliminates biased interpretation associated with human evaluation; it can be applied to any chosen method of image registration. Our method involves using planning computed tomography (PCT) images acquired with a conventional CT simulator and cone-beam computed tomography (CBCT) images acquired daily by a linear accelerator-mounted kilovoltage image system in the treatment delivery room. The deformation that occurs between the PCT and daily CBCT images is obtained using a modified version of the B-Spline deformable model designed to overcome the low soft-tissue contrast and the artifacts and distortions observed in CBCT images. Clinical CBCT images and contours of phantom and central nervous system cases were deformed (warped) with known random deformations. In registering the deformed with the non-deformed image sets, we tracked the algorithm's ability to recover the original, non-deformed set. Registration error was measured as the mean and maximum difference between the original and the registered surface contours from outlined structures. Using this approach, two sets of tests can be devised. To measure the residual error related to the optimizer's convergence performance, the warped CBCT image is registered to the unwarped version of itself, eliminating unknown factors such as noise and positioning errors. To study additional errors introduced by artifacts and noise in the CBCT image, the warped CBCT image is registered to the original PCT image. Using a B-Spline deformable image registration algorithm, mean residual error introduced by the algorithm's performance on noise-free images was less than 1 mm, with a maximum of 2 mm. The chosen deformable image registration model was capable of accommodating significant variability in structures over time, because the artificially introduced deformation magnitude did not significantly influence the residual error. On the second type of test, noise and artifacts reduced registration accuracy to a mean of 1.33 mm and a maximum of 4.86 mm. The accuracy of deformable image registration can be easily and consistently measured by evaluating the algorithm's ability to recover artificially introduced deformations in rigid cases in which the true solution is known a priori. The method is completely automated, applicable to any chosen registration algorithm, and does not require user interaction of any kind.

For 2018, the American Cancer Society estimated that there would be approximately 1.7 million new diagnoses of cancer and about 609,640 cancer-related deaths in the United States. By 2030 these numbers are anticipated to exceed a staggering 21 million annual diagnoses and 13 million cancer-related deaths. The three primary therapeutic modalities for cancer treatments are surgery, chemotherapy, and radiation therapy. Individually or in combination, these treatment modalities have provided and continue to provide curative and palliative care to the myriad victims of cancer. Today, CT-based treatment planning is the primary means through which conventional photon radiation therapy is planned. Although CT remains the primary treatment planning modality, the field of radiation oncology is moving beyond the sole use of CT scans to define treatment targets and organs at risk. Complementary tissue scans, such as magnetic resonance imaging (MRI) and positron electron emission (PET) scans, have all improved a physician's ability to more specifically identify target tissues, and in some cases, international guidelines have even been issued. Moreover, efforts to combine PET and MR to define solid tumors for radiotherapy planning and treatment evaluation are also gaining traction. Keeping these advances in mind, we present brief overviews of other up-and-coming key imaging concepts that appear promising for initial treatment target definition or treatment response from radiation therapy.

Background: Ultrahypofractionation using stereotactic body radiotherapy (SBRT) is an increasingly utilized technique for men with prostate cancer (PC). The comparative efficacy of SBRT plus androgen deprivation therapy (ADT) compared to fractionated radiotherapy (EBRT) plus ADT in higher-risk prostate cancer is unknown. Methods: Men > 40 years old with localized PC treated with external beam radiation and concomitant ADT for curative intent between 2004 and 2016 were analyzed from the National Cancer Database. Patients who lacked ADT or risk stratification data were excluded. 558 men treated with SBRT versus 40,797 men treated with conventional or moderately hypofractionated EBRT were included. Patients were stratified by unfavorable intermediate (UIR) and high (HR) risk using NCCN criteria. Kaplan Meier and Cox proportional hazards were used to compare overall survival (OS) between RT modality, adjusting for age, race, and comorbidity index. Results: With a median follow up of 74 months, there was no difference in estimated 6-year OS between men treated with SBRT versus EBRT regardless of risk group. On multivariable analysis, there was no difference in risk of death for men treated with SBRT compared to EBRT (UIR: adjusted HR 1.09, 95% CI 0.68-1.74, p =.72; HR: adjusted HR 0.93, 95% CI 0.76-1.14, p =.51). On sensitivity analyses, when confining the cohort to men treated with NCCN-preferred dose fractionations, with no comorbidities, or < 65 years old, there remained no survival difference between treatment groups for both UIR and HR. Conclusion: Within study limitations, we found no difference in survival between SBRT+ADT and standard of care EBRT+ADT for UIR or HR PC. These results support recent NCCN guideline updates, which include SBRT as a non-preferred option for higher risk men. Prospective validation would further strengthen the evidence basis behind these recommendations.