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Background: Accurate risk stratification is critical to guide management decisions in localized prostate cancer (PCa). Previously, we had developed and validated a multimodal artificial intelligence (MMAI) model generated from digital histopathology and clinical features. Here, we externally validate this model on men with high-risk or locally advanced PCa treated and followed as part of a phase 3 randomized control trial., Objective: To externally validate the MMAI model on men with high-risk or locally advanced PCa treated and followed as part of a phase 3 randomized control trial., Design, Setting, and Participants: Our validation cohort included 318 localized high-risk PCa patients from NRG/RTOG 9902 with available histopathology (337 [85%] of the 397 patients enrolled into the trial had available slides, of which 19 [5.6%] failed due to poor image quality)., Outcome Measurements and Statistical Analysis: Two previously locked prognostic MMAI models were validated for their intended endpoint: distant metastasis (DM) and PCa-specific mortality (PCSM). Individual clinical factors and the number of National Comprehensive Cancer Network (NCCN) high-risk features served as comparators. Subdistribution hazard ratio (sHR) was reported per standard deviation increase of the score with corresponding 95% confidence interval (CI) using Fine-Gray or Cox proportional hazards models., Results and Limitations: The DM and PCSM MMAI algorithms were significantly and independently associated with the risk of DM (sHR [95% CI] = 2.33 [1.60-3.38], p < 0.001) and PCSM, respectively (sHR [95% CI] = 3.54 [2.38-5.28], p < 0.001) when compared against other prognostic clinical factors and NCCN high-risk features. The lower 75% of patients by DM MMAI had estimated 5- and 10-yr DM rates of 4% and 7%, and the highest quartile had average 5- and 10-yr DM rates of 19% and 32%, respectively (p < 0.001). Similar results were observed for the PCSM MMAI algorithm., Conclusions: We externally validated the prognostic ability of MMAI models previously developed among men with localized high-risk disease. MMAI prognostic models further risk stratify beyond the clinical and pathological variables for DM and PCSM in a population of men already at a high risk for disease progression. This study provides evidence for consistent validation of our deep learning MMAI models to improve prognostication and enable more informed decision-making for patient care., Patient Summary: This paper presents a novel approach using images from pathology slides along with clinical variables to validate artificial intelligence (computer-generated) prognostic models. When implemented, clinicians can offer a more personalized and tailored prognostic discussion for men with localized prostate cancer., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Trimodality therapy for muscle-invasive bladder cancer (MIBC) yields similar oncologic outcomes compared to radical cystectomy in appropriately selected patients; however, data regarding locally advanced MIBC (LA-MIBC) is limited. We explored our experience with LA-MIBC undergoing radiation therapy (RT)., Methods: We retrospectively identified 30 patients from an institutional prospectively collated database with non-metastatic, LA-MIBC. Patients with T3-4 N0 or T2-4 N + treated from 2012 to 2022 with definitive-intent RT, who were not candidates for cystectomy were included. Kaplan-Meier analysis was used to estimate time-to-event outcomes, and multivariate analyses were conducted using Cox proportional hazards modeling., Results: 43 % had T3N0 disease, 30 % had T4N0 disease, and 27 % had node positive disease.. Neoadjuvant chemotherapy/systemic therapy was administered in 63 % of patients. Median dose and fractionation of RT was 60 Gy in 30 fractions. 23 % of patients received hypofractionated RT, 57 % received nodal RT.At a median follow-up of 20 (range, 1-75) months after RT, estimated 1- and 2-year OS was 73 % and 61 %, respectively. Estimated 1-year progression-free survival was 50 %. Local bladder failure was a component of progression in 17 % of patients, and all local bladder failure events occurred within the first 12 months following RT. Lymph node or distant metastases occurred in 23 % of patients. Estimated 1-year OS was 83 % with pure urothelial histology but only 58 % with variant histology (P = 0.001). Late grade 3 + GU and GI toxicity occurred in 7 % and 5 % of patients, respectively., Conclusions: In this cohort with LA-MIBC treated with RT, distant failures predominate, local failures are less common, and toxicity was minimal. Survival outcomes remain encouraging for RT in this challenging patient population. Further investigation is warranted to identify biomarkers for patient selection and strategies to improve distant control., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Purpose: CT Hounsfield Units (HUs) are converted to electron density using a calibration curve obtained from physical measurements of an electron density phantom. HU values assigned to an MRI-derived synthetic computed tomography (sCT) may present a different relationship with electron density compared to CT HU. Correct assignment of sCT HU values is critical for accurate dose calculation and delivery. The goals of this work were to develop a sCT calibration curve using patient data acquired on a clinically commissioned CT scanner and assess for CyberKnife- and volumetric modulated arc therapy (VMAT)-based MR-only treatment planning of prostate SBRT., Methods: Same-day CT and MRI simulation in the treatment position were performed on 10 patients treated with SBRT to the prostate. Dixon in-phase and out-of-phase MRIs were acquired on a 3T scanner using a 3D T1-weighted gradient-echo sequence to generate sCTs using a commercial sCT algorithm. CT and sCT datasets were co-registered and HU values compared using mean absolute error (MAE). An optimized HU-to-density calibration curve was created based on average HU values across an institutional patient database for each of the four sCT tissue types. Clinical CyberKnife and VMAT treatment plans were generated on each patient CT and recomputed onto corresponding sCTs. Dose distributions computed using CT and sCT were compared using gamma criteria and dose-volume-histograms., Results: For the optimized calibration curve, HU values were -96, 37, 204, and 1170 and relative electron densities were 0.95, 1.04, 1.1, and 1.7 for adipose, soft tissue, inner bone, and outer bone, respectively. The proposed sCT protocol produced total MAE of 94 ± 20HU. Gamma values mean ± std (min-max) were 98.9% ± 0.9% (97.1%-100%) and 97.7% ± 1.3% (95.3%-99.3%) for VMAT and CyberKnife plans, respectively., Conclusion: MRI-derived sCT using the proposed approach shows excellent dosimetric agreement with conventional CT simulation, demonstrating the feasibility of MRI-derived sCT for prostate SBRT treatment planning., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Introduction: Enzalutamide, a second-generation androgen receptor inhibitor, is indicated for the treatment of metastatic disease, as well as in the treatment of non-metastatic castration resistant prostate cancer (PCa). This systematic review aims to determine outcomes and toxicity in patients with non-metastatic castration sensitive prostate cancer (nmCSPC) treated with enzalutamide in the primary or salvage settings., Method: We performed a systematic review focusing on the role of Enzalutamide in the treatment of nmCSPC, using the PubMed/Medline database. Articles focusing on androgen receptor inhibitors in nmCSPC were included, while articles discussing exclusively metastatic or castration-resistant PCa were excluded., Results: The initial search retrieved 401 articles, of which 15 underwent a thorough assessment for relevance. Ultimately, 12 studies with pertinent outcomes were meticulously examined. Among these, seven studies were dedicated to the investigation of enzalutamide in the primary setting, while the remaining five publications specifically addressed its use in salvage settings. Regardless of the treatment setting, our data revealed two distinct therapeutic strategies. The first advocates for the substitution of enzalutamide for androgen deprivation therapy (ADT), based on the premise of achieving equivalent, if not superior, oncological outcomes while minimizing treatment-related toxicity. The second, adopting a more conventional approach, entails augmenting the effectiveness of ADT by incorporating enzalutamide., Conclusion: Enzalutamide has considerable potential as a therapeutic strategy for nmCSPC, either used alone or in combination with ADT in the primary or in the salvage settings. The use of enzalutamide instead of ADT is an appealing strategy. However, more trials will be required to further understand the efficacy and side-effect profile of enzalutamide monotherapy., (© 2024. The Author(s).)

Delays in the work-up and definitive management of patients with prostate cancer are common, with logistics of additional work-up after initial prostate biopsy, specialist referrals, and psychological reasons being the most common causes of delays. During the COVID-19 pandemic and the subsequent surges, timing of definitive care delivery with surgery or radiotherapy has become a topic of significant concern for patients with prostate cancer and their providers alike. In response, recommendations for the timing of definitive management of prostate cancer with radiotherapy and radical prostatectomy were published but without a detailed rationale for these recommendations. While the COVID-19 pandemic is behind us, patients are always asking the question: "When should I start radiation or undergo surgery?" In the absence of level I evidence specifically addressing this question, we will hereby present a narrative review to summarize the available data on the effect of treatment delays on oncologic outcomes for patients with localized prostate cancer from prospective and retrospective studies., (© 2024. The Author(s).)

Background: The health-care industry is a substantial contributor to global greenhouse gas emissions, yet the specific environmental impact of radiotherapy, a cornerstone of cancer treatment, remains under-explored. We aimed to quantify the emissions associated with the delivery of radiotherapy in the USA and propose a framework for reducing the environmental impact of oncology care., Methods: In this multi-institutional retrospective analysis and simulation study, we conducted a lifecycle assessment of external beam radiotherapy (EBRT) for ten anatomical disease sites, adhering to the International Organization for Standardization's standards ISO 14040 and ISO 14044. We analysed retrospective data from Jan 1, 2017, to Oct 1, 2023, encompassing patient and staff travel, medical supplies, and equipment and building energy use associated with the use of EBRT at four academic institutions in the USA. The primary objective was to measure the environmental impacts across ten categories: greenhouse gases (expressed as kg of carbon dioxide equivalents [CO 2 e]), ozone depletion, smog formation, acidification, eutrophication, carcinogenic and non-carcinogenic potential, respiratory effects, fossil fuel depletion, and ecotoxicity. Human health effects secondary to these environmental impacts were also estimated as disability-adjusted life years. We also assessed the potential benefits of hypofractionated regimens for breast and genitourinary (ie, prostate and bladder) cancers on US greenhouse gas emissions using an analytic model based on the 2014 US National Cancer Database for fractionation patterns and patient commute distances., Findings: We estimated that the mean greenhouse gas emissions associated with a standard 25-fraction EBRT course were 4310 kg CO 2 e (SD 2910), which corresponded to 0·0035 disability-adjusted life years per treatment course. Transit and building energy usage accounted for 25·73% (1110 kg CO 2 e) and 73·95% of (3190 kg CO 2 e) of total greenhouse gas emissions, respectively, whereas supplies contributed only 0·32% (14 kg CO 2 e). Across the other environmental impact categories, most of the environmental impact also stemmed from patient transit and energy use within facilities, with little environmental impact contributed by supplies used. Hypofractionated treatment simulations suggested a substantial reduction in greenhouse gas emissions-by up to 42% for breast and 77% for genitourinary cancer-and environmental impacts more broadly., Interpretation: This comprehensive lifecycle assessment of EBRT delineates the environmental and secondary health impacts of radiotherapy, and underscores the urgent need for sustainable practices in oncology. The findings serve as a reference for future decarbonisation efforts in cancer care and show the potential environmental benefits of modifying treatment protocols (when clinical equipoise exists). They also highlight strategic opportunities to mitigate the ecological footprint in an era of escalating climate change and increasing cancer prevalence., Funding: Mount Zion Health Fund., Competing Interests: Declaration of interests CLT has received honoraria from Clinically Sustainable Consulting and financial support from Vizient, and has held leadership roles with the New York University Stern School of Business Center for Sustainable Business, the Centre for Sustainable Healthcare, EyeSustain, and Mass General Center for Climate and Health. JC has been a paid consultant for Stryker and Guidepoint, has received honoraria from Gynecologic Oncology Group Foundation, has received compensation in exchange for services and expertise from KM Pharmaceutical Consulting and Merck, and is member of the American Brachytherapy Society. SSY has received research support grants from EMD Serono and Bristol-Myers Squibb, royalties from UpToDate and Springer, and honoraria from the American Society of Radiation Oncology and Elsevier. All other authors declare no competing interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: In this systematic review and meta-analysis, we describe the oncologic and toxicity outcomes of definitive focal brachytherapy for prostate cancer., Methods and Materials: A PROSPERO registered study (CRD42023410170) was conducted following the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. PubMed, Embase, and The Cochrane Library were searched for studies between 2000 and 2022. Two authors independently performed the initial search. Biochemical recurrence-free survival (bRFS) was defined as the primary endpoint for the meta-analysis. Generalized linear mixed-effects models were conducted to calculate effect size and quantify heterogeneity. We also describe the side effects and local recurrence patterns of focal brachytherapy., Results: Ten studies were identified and included 315 patients treated using focal brachytherapy as a definitive treatment. Mean (SD) age was 67.65 (7.9) years and mean (SD) PSA was 7.15 (2.7) ng/mL. Most patients (n = 236, 75%) underwent LDR Brachytherapy and 25% received HDR brachytherapy. Among the participants, 147 (46.5%) had a Gleason score ≤6, and 169 (53.5%) had a Gleason score ≥7. Only 11 (3.5%) patients received ADT. Overall, bRFS rate at median follow-up 4 years (Range: 1-6.42 years) was 91% (95% confidence interval [CI], 82-95%). Acute Grade ≤ 2 GU and GI toxicities were reported in 22 (7%) and 11 (3.5%) patients, respectively. Late Grade ≤ 2 GU and GI toxicity were reported in 6 (2%) and 14 (4.4%) patients, respectively. One case of prostate hemorrhage due to improper foley removal was noted but otherwise no acute or late Grade 3 or higher GI or GU toxicity related to radiotherapy was reported., Conclusion: Overall, definitive focal brachytherapy has a favorable toxicity profile. Oncologic outcomes are yet to mature. The evidence is limited by the small number of studies with low patients' number, across study heterogeneity, and possibility of publication bias., (Copyright © 2024 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: This systematic review and meta-analysis aimed to evaluate the evidence for ultrahypofractionated pelvic nodal irradiation in patients with prostate cancer, with a focus on reported acute and late toxicities., Methods and Materials: A comprehensive search was conducted in 5 electronic databases (PubMed, Scopus, Web of Science, Cochrane Library, ClinicalTrials.gov) from inception until March 23, 2023. Eligible publications included patients with intermediate- and high-risk and node-positive prostate cancer who underwent elective or therapeutic ultrahypofractionated pelvic nodal irradiation. Primary outcomes included the presence of grade ≥2 rates of acute and late gastrointestinal and genitourinary toxicity based on the Common Terminology Criteria for Adverse Events or Radiation Therapy Oncology Group scales. Quality assessment was performed using National Institutes of Health tools for noncontrolled beforeand after (single arm) clinical trials, as well as single-arm observational studies. Because all outcomes were categorical variables, proportion was calculated to estimate the effect size and compare the outcomes after the intervention., Results: We identified 16 publications that reported the use of ultrahypofractionated radiation therapy to treat the pelvis in prostate cancer. Seven publications met our criteria and were included in the meta-analysis, including 417 patients. The median total dose to the pelvic lymph nodes was 25 Gy (range, 25-28.5 Gy), with a median of 5 fractions. The prostate received a median dose of 40 Gy (range, 35-47.5 Gy). All studies used androgen deprivation therapy for a median duration of 18 months. The median follow-up period was 3 years (range, 0.5-5.6 years). The rates of acute grade ≥2 gastrointestinal and genitourinary toxicity were 8% (95% CI, 1%-15%) and 29% (95% CI, 18%-41%), respectively. For late grade ≥2 gastrointestinal and genitourinary toxicity, the rates were 13% (95% CI, 5%-21%) and 29% (95% CI, 17%-42%), respectively., Conclusions: Ultrahypofractionated pelvic nodal irradiation appears to be a safe approach in terms of acute and late genitourinary and gastrointestinal toxicity., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: This study aimed to systematically review the literature on the travel patterns of patients seeking radiation therapy globally. It examined the distance patients travel for radiation therapy as well as secondary outcomes, including travel time., Methods and Materials: A comprehensive search of 4 databases was conducted from June 2022 to August 2022. Studies were included in the review if they were observational, retrospective, randomized/nonrandomized, published between June 2000 and June 2022, and if they reported on the global distance traveled for radiation therapy in the treatment of malignant or benign disease. Studies were excluded if they did not report travel distance or were not written in English., Results: Of the 168 studies, most were conducted in North America (76.3%), with 90.7% based in the United States. Radiation therapy studies for treating patients with breast cancer were the most common (26.6%), while external beam radiation therapy was the most prevalent treatment modality (16.6%). Forty-six studies reported the mean distance traveled for radiation therapy, with the shortest being 4.8 miles in the United States and the longest being 276.5 miles in Iran. It was observed that patients outside of the United States traveled greater distances than those living within the United States. Geographic location, urban versus rural residence, and patient population characteristics affected the distance patients traveled for radiation therapy., Conclusions: This systematic review provides the most extensive summary to date of the travel patterns of patients seeking radiation therapy globally. The results suggest that various factors may contribute to the variability in travel distance patterns, including treatment center location, patient residence, and treatment modality. Overall, the study highlights the need for more research to explore these factors and to develop effective strategies for improving radiation therapy access and reducing travel burden., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: A history of prior pelvic radiation therapy (RT) for rectal cancer is a relative contraindication for definitive RT for prostate cancer. High-dose-rate (HDR) brachytherapy can significantly limit the dose to surrounding tissues compared to external beam RT. However, there is limited data surrounding its safety in patients with prior pelvic RT., Methods and Materials: A retrospective chart review was performed at the University of California, San Francisco to identify patients diagnosed with prostate cancer with a history of pelvic RT for rectal cancer who were treated with high-dose-rate brachytherapy (HDR-BT) between 2006 and 2022. Inclusion criteria were biopsy-confirmed prostate cancer with no evidence of distant disease on clinical examination or imaging, and at least one post-treatment clinic appointment., Results: Seven patients were treated with salvage HDR-BT at a median interval of 17.7 years after RT for rectal cancer. HDR-BT doses included 3600 cGy in six fractions (n = 5), 2700 cGy in 2 fractions (n=1), or 2800 cGy in four fractions (n = 1). There was no acute grade ≥2 gastrointestinal toxicity, and 1 patient developed late grade 2 rectal bleeding. Two patients developed acute grade 2 genitourinary toxicity consisting of urinary frequency and urgency, which persisted through long-term follow up. At a median follow up of 29.5 months after HDR brachytherapy, one patient developed regional and distant failure, and another had seminal vesicle recurrence., Conclusions: HDR-BT is a safe treatment for patients with prostate cancer who previously received RT for rectal cancer. Further studies are needed to better characterize the long-term toxicity of HDR-RT in this population., (Copyright © 2023 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

A secondary analysis of 2 randomized Radiation Therapy Oncology Group trials demonstrated that age ≥70 years was a favorable prognostic factor among men treated with external beam radiation therapy (EBRT). In contrast, several series based on men undergoing radical prostatectomy (RP) suggested that older age was an unfavorable prognostic factor. Our study was initiated to determine whether these observations reflect a true but paradoxical underlying age-related treatment-dependent biological phenomenon. We conducted a systematic review (PubMed, January 1, 1999-January 30, 2023) evaluating the effect of age on cancer-specific outcomes after definitive local treatment with either RP or EBRT. Our main objective was to assess possible interactions between age (using a cutoff of 70 +/- 5 years) and treatment type, with regard to adverse cancer-specific outcomes (eg, pathology, biochemical failure, distant metastasis, or prostate cancer-specific survival). Forty-five studies were selected for inclusion in this systematic review, including 30 and 15 studies with patients treated with RP and EBRT, respectively. Among patients treated with RP, 10 (50%) of these studies suggested that older age was associated with worse outcome(s) after RP. None suggested that age was a favorable prognostic factor after RP. Among the EBRT-based studies, 8 (53%) suggested that older age was associated with better outcomes, with an additional 3 studies (21%) trending to support a better outcome. None of these studies involving EBRT suggested that older age was an adverse prognostic factor. This systematic review suggests that age using a categorical cutoff of 70 +/- 5 years may be an adverse prognostic factor for men undergoing RP but a favorable prognostic factor for men treated with EBRT. Further research is needed to validate these findings., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: 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., Material and Methods: 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., Results: 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., Conclusions: 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., Competing Interests: The authors report no conflict of interest., (Copyright © 2023 Termedia.)

Purpose: We aimed to examine the impact of different conference formats (in-person, virtual, and hybrid) of the ASCO conference on greenhouse gas (GHG) emissions and to recommend sustainable options for future conferences., Materials and Methods: This study used data on the number of attendees, their departure locations, and the type of attendance (in-person v virtual) provided by ASCO between 2019 and 2022. The GHG emissions resulting from air and ground travel, remote connectivity, conference space utilization, hotel stays, distributed conference materials, and electricity use were estimated for each year. Emissions were stratified by attendee country of origin, type of attendance, and year. Simulations were conducted to evaluate how changes in conference size, location, and format impact emissions, as well as estimate the resulting mitigations from adopting the proposed changes., Results: The highest estimated GHG emissions, calculated in carbon dioxide equivalents (CO 2 e), were associated with the 2019 in-person conference (37,251 metric tons of CO 2 e). Although international attendees had the largest contribution to emissions in all years (>50%), location optimization models, which selected conference locations that most minimized GHG emissions, yielded only minimal reductions (approximately 3%). Simulations examining changes to the conference format, location, and attendance percentage suggested that hub-and-spoke, where multiple conference locations are selected by global region, or hybrid models, with both in-person and virtual components, are likely to cause the largest drops in emissions (up to 86%)., Conclusion: Using historical conference data, this study identifies key aspects that can be modified to reduce emissions and consequently promote more sustainable and equitable conference attendance. Hybrid conferences may be the best solution to maintain the networking opportunities provided by conferences while balancing out their environmental footprint.

Background: Up to 40% of patients with prostate cancer may develop biochemical recurrence after surgery, with salvage radiation therapy (SRT) being the only curative option. In 2016, Tendulkar et al. (Contemporary update of a multi-institutional predictive nomogram for salvage radiotherapy after radical prostatectomy. J Clin Oncol 2016;34:3648-54) published a nomogram to predict distant metastasis in a cohort of patients treated with SRT with pre-SRT prostate-specific antigen (PSA) of 0.5 ng/ml after radical prostatectomy. In modern practice, SRT is delivered at lower PSA values., Objective: To train and externally validate a machine learning model to predict the risk of distant metastasis at 5 yr in a contemporary cohort of patients receiving SRT., Design, Setting, and Participants: We trained a machine learning model on data from 2418 patients treated with SRT at one institution, with a median PSA value of 0.27 ng/ml. External validation was done in 475 patients treated at two different institutions. Patients with cM1, pN1, or pT4 disease were excluded, as were patients with PSA >2 ng/ml or PSA 0, and patients with radiation dose <60 or ≥80 Gy., Outcome Measurements and Statistical Analysis: Model performance was assessed using calibration and time-dependent area under the receiver operating curve (tAUC)., Results and Limitations: Our model had better calibration and showed improved discrimination (tAUC = 0.72) compared with the Tendulkar model (tAUC = 0.60, p < 0.001). The main limitations of this study are its retrospective design and lack of validation on patients who received hormone therapy., Conclusions: The updated model can be used to provide more individualized risk assessments to patients treated with SRT at low PSA values, improving decision-making., Patient Summary: Up to 40% of patients with prostate cancer may develop biochemical recurrence after surgery, with salvage radiation therapy as the only potentially curative option. We trained and validated a machine learning model using clinical and surgical data to predict a patient's risk of distant metastasis at 5 yr after treatment. Our model outperformed the reference tool and can improve clinical decision-making by providing more personalized risk assessment., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Concurrent increases in global cancer burden and the climate crisis pose an unprecedented threat to public health and human well-being. Today, the health care sector greatly contributes to greenhouse gas emissions, with the future demand for health care services expected to rise. Life cycle assessment (LCA) is an internationally standardized tool that analyzes the inputs and outputs of products, processes, and systems to quantify associated environmental impacts. This critical review explains the use of LCA methodology and outlines its application to external beam radiation therapy (EBRT) with the aim of providing a robust methodology to quantify the environmental impact of radiation therapy care practices today. The steps of an LCA are outlined and explained as defined by the International Organization for Standardization (ISO 14040 and 14044) guidelines: (1) definition of the goal and scope of the LCA, (2) inventory analysis, (3) impact assessment, and (4) interpretation. The existing LCA framework and its methodology is described and applied to the field of radiation oncology. The goal and scope of its application to EBRT is the evaluation of the environmental impact of a single EBRT treatment course within a radiation oncology department. The methodology for data collection via mapping of the resources used (inputs) and the end-of-life processes (outputs) associated with EBRT is explained, with subsequent explanation of the LCA analysis steps. Finally, the importance of appropriate sensitivity analysis and the interpretations that can be drawn from LCA results are reviewed. This critical review of LCA protocol provides and evaluates a methodological framework to scientifically establish baseline environmental performance measurements within a health care setting and assists in identifying targets for emissions mitigation. Future LCAs in the field of radiation oncology and across medical specialties will be crucial in informing best practices for equitable and sustainable care in a changing climate., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The effect of climate-driven events, such as wildfires, on health care delivery and cancer care is a growing concern. Patients with cancer undergoing radiation therapy are particularly vulnerable to treatment interruptions, which have a direct effect on survival. We report the results of a study characterizing the effect of wildfires on radiation oncology clinics and their patients., Methods and Materials: A survey of California radiation oncologists was used to evaluate emergency preparedness and the effect of wildfires on the delivery of radiation therapy services between 2017 and 2022. Descriptive statistics and Pearson's χ 2 tests were performed to investigate potential relationships between provider characteristics, practice settings, and perceptions of the effect of wildfire events. California Department of Forestry and Fire Protection data were employed to map the geographic distribution of wildfires to clinic locations., Results: Response rate was 12.3% (51/415 radiation oncologists), representing 25% of clinics (43/176) in 41% (24/58) of California counties. Sixty-one percent (31/51) of respondents reported being affected by a wildfire, 2 of which are rural clinics (100%, 2/2) and 29 are (59%, 29/49) metropolitan practices. Of these, 18% (9/51) reported a clinic closure, and 29% (15/51) reported staffing shortages. Respondents reported effects on patients, including having to evacuate (55%, 28/51), cancel/reschedule treatments (53%, 27/51), and experiencing physical, mental, or financial hardship due to wildfires (45%, 23/51). Respondents described effects on clinical operations, including being forced to transfer patients (24%, 12/51), transportation interruptions (37%, 19/51), regional/community evacuations (35%, 18/51), and physical/mental health effects (27%, 14/51) on clinic personnel. Less than half of the respondents (47%, 24/51) reported their workplace had a wildfire emergency preparedness plan. Additionally, geographic analysis revealed that 100% (176/176) of clinics were located within 25 miles of a wildfire., Conclusions: This study highlights the effects of wildfires on radiation oncology clinics and patients and underscores the need for emergency preparedness planning to minimize the consequences of such disasters., Competing Interests: James Bates reports being on advisory boards for Galera Therapeutics and Castle Biosciences. Sue Yom reports grants/contracts with EMD Serono and Bristol-Myers Squibb), and payment/honoraria from Up To Date, Springer, Elsevier, and ASTRO., (© 2023 The Authors.)

Background: Pelvic lymph node dissection (PLND) is the gold standard for diagnosis of lymph node involvement (LNI) in patients with prostate cancer. The Roach formula, Memorial Sloan Kettering Cancer Center (MSKCC) calculator, and Briganti 2012 nomogram are elegant and simple traditional tools used to estimate the risk of LNI and select patients for PLND., Objective: To determine whether machine learning (ML) can improve patient selection and outperform currently available tools for predicting LNI using similar readily available clinicopathologic variables., Design, Setting, and Participants: Retrospective data for patients treated with surgery and PLND between 1990 and 2020 in two academic institutions were used., Outcome Measurements and Statistical Analysis: We trained three models (two logistic regression models and one gradient-boosted trees-based model [XGBoost]) on data provided from one institution (n = 20267) with age, prostate-specific antigen (PSA) levels, clinical T stage, percentage positive cores, and Gleason scores as inputs. We externally validated these models using data from another institution (n = 1322) and compared their performance to that of the traditional models using the area under the receiver operating characteristic curve (AUC), calibration, and decision curve analysis (DCA)., Results and Limitations: LNI was present in 2563 patients (11.9%) overall, and in 119 patients (9%) in the validation data set. XGBoost had the best performance among all the models. On external validation, its AUC outperformed that of the Roach formula by 0.08 (95% confidence interval [CI] 0.042-0.12), the MSKCC nomogram by 0.05 (95% CI 0.016-0.070), and the Briganti nomogram by 0.03 (95% CI 0.0092-0.051; all p < 0.05). It also had better calibration and clinical utility in terms of net benefit on DCA across relevant clinical thresholds. The main limitation of the study is its retrospective design., Conclusions: Taking all measures of performance together, ML using standard clinicopathologic variables outperforms traditional tools in predicting LNI., Patient Summary: Determining the risk of cancer spread to the lymph nodes in patients with prostate cancer allows surgeons to perform lymph node dissection only in patients who need it and avoid the side effects of the procedure in those who do not. In this study, we used machine learning to develop a new calculator to predict the risk of lymph node involvement that outperformed traditional tools currently used by oncologists., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: To report objective long-term complications and health related quality of life (HRQOL) outcomes after radical prostatectomy (RP) with and without radiation therapy (RT) for prostate cancer (CaP)., Methods: We analyzed patients diagnosed with CaP who underwent RP from the UCSF Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry between 1995 and 2020. Cox proportional hazards were used to assess risk of postoperative complications which included cystitis, gastrointestinal (GI) toxicity, incontinence requiring a surgical procedure, ureteral injury and urinary stricture. Repeated measures mixed models were used to assess the effects of radiation and complications on patient-reported urinary, bowel, and sexual function after surgery., Results: Of 6,258 men who underwent RP, cumulative incidence of EBRT was 9.1% at 5 years after surgery. Patients who received postoperative radiation were at increased risk for onset of cystitis (HR 5.60, 95% CI 3.40-9.22, P < 0.01). Receipt of RT was not associated with other complications. In repeated measures analysis, postoperative RT was associated with worsening general health scores, adjusting for complications of incontinence, urinary stricture, GI toxicity or ureteral injury, independent of whether patients had those complications., Conclusions: RT after RP was associated with an increase in the risk of cystitis and worse general health in the long term. Other complications and HRQOL outcomes did not demonstrate differences by whether patients had RT or not. While post-operative RT is the only curative option for CaP after RP, patients and providers should be aware of the increased risks when making treatment decisions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Although vertebroplasty is a well-known treatment for osteoporotic and neoplastic compression fractures, there is limited evidence to support its use in traumatic compression fractures without osteoporotic degeneration. The purpose of this study was to evaluate the correlation of kyphosis and wedge angles with pain relief and functional outcome after percutaneous vertebroplasty. 38 patients who harbored acute traumatic non-osteoporotic compression vertebral fractures without neurological complications refractory to at least 5 days of conservative treatment were included in this study. Follow-up evaluations included pain (assessed with the visual analog scale) and medication use. Functional outcome was measured using Oswestry low back pain disability questionnaire. Cobb angles, Gardner angles and kyphotic angles were measured on the full-spine radiographs preoperatively and postoperatively. The axial pain visual analog scale score (8.05 ± 1.23 pre-op vs 1.18 ± 1.09 post-op, P < .05) and The Oswestry low back pain disability questionnaire score (33.45 ± 6.97 pre-op vs 4.47 ± 2.41 post-op, P < .05). The Cobb's angle (19.66° ± 8.68° pre-op vs 15.08° ± 7.51° post-op, P < .05), the Gardner's angle (17.72° ± 6.52° pre-op vs 14.13° ± 7.13° post-op, P < .05) and the kyphotic angle (17.51° ± 5.8° pre-op vs 8.81° ± 4.14°post-op, P < .05) were significantly reduced postoperatively therefore, local kyphosis was markedly restored after vertebroplasty. Our findings show that vertebroplasty for patients with traumatic spinal compression fractures reduces pain, improves mobility, reduces the need for painkillers, and significantly affects kyphotic angles., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To assess the long-term incidence of treatment-related toxicities and quality of life (QOL) outcomes associated with toxicity after external beam radiotherapy (EBRT) for prostate cancer., Methods: We identified all men who had EBRT between 1994 and 2017 from Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a longitudinal, nationwide prostate cancer registry. CaPSURE was queried for patient-reported and International Classification of Diseases-9/10 and Current Procedural Terminology codes. The Medical Outcomes Studies Short Form 36 and the University of California, Los Angeles Prostate Cancer Index were used to provide measures of general health, sexual, urinary, and bowel function. Repeated measures mixed models were used to determine QOL change after onset of toxicity., Results: From a total of 15,332, 1744 (11.4%) men had EBRT. The median follow-up was 7.9years (interquartile range [IQR] 4.3-12.7). The median time to onset of any toxicity including urinary pad usage in 265 (15.4% at 8years) men was 4.3years (IQR 1.8-8.0). The most frequent toxicity was hemorrhagic cystitis (104, 5.9% at 8years) after a median of 3.7years (1.3-7.8), gastrointestinal (48, 2.7% at 8years) after a median of 4.2years (IQR 1.3-7.8), followed by urethral stricture (47, 2.4% at 8years) after a median of 3.7years (IQR 1.9-9.1). Repeated measures mixed models found that onset of hemorrhagic cystitis was associated with change in general health over time., Conclusion: EBRT for prostate cancer is associated with distinct treatment-related toxicities which can occur many years after treatment and can affect QOL. These results may help men understand the long-term implications of treatment decisions., Competing Interests: DECLARATION OF COMPETING INTEREST The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

BACKGROUND: Androgen deprivation therapy (ADT) with radiotherapy can benefit patients with localized prostate cancer. However, ADT can negatively impact quality of life, and there remain no validated predictive models to guide its use. METHODS: We used digital pathology images from pretreatment prostate tissue and clinical data from 5727 patients enrolled in five phase 3 randomized trials, in which treatment was radiotherapy with or without ADT, as our data source to develop and validate an artificial intelligence (AI)–derived predictive patient-specific model that would determine which patients would develop the primary end point of distant metastasis. The model used baseline data to provide a binary output that a given patient will likely benefit from ADT or not. After the model was locked, validation was performed using data from NRG Oncology/Radiation Therapy Oncology Group (RTOG) 9408 (n=1594), a trial that randomly assigned men to radiotherapy plus or minus 4 months of ADT. Fine–Gray regression and restricted mean survival times were used to assess the interaction between treatment and the predictive model and within predictive model–positive, i.e., benefited from ADT, and –negative subgroup treatment effects. RESULTS: Overall, in the NRG/RTOG 9408 validation cohort (14.9 years of median follow-up), ADT significantly improved time to distant metastasis. Of these enrolled patients, 543 (34%) were model positive, and ADT significantly reduced the risk of distant metastasis compared with radiotherapy alone. Of 1051 patients who were model negative, ADT did not provide benefit. CONCLUSIONS: Our AI-based predictive model was able to identify patients with a predominantly intermediate risk for prostate cancer likely to benefit from short-term ADT. (Supported by a grant [U10CA180822] from NRG Oncology Statistical and Data Management Center, a grant [UG1CA189867] from NCI Community Oncology Research Program, a grant [U10CA180868] from NRG Oncology Operations, and a grant [U24CA196067] from NRG Specimen Bank from the National Cancer Institute and by Artera, Inc. ClinicalTrials.gov numbers NCT00767286, NCT00002597, NCT00769548, NCT00005044, and NCT00033631.)

Objective: To systematically aggregate and summarize existing data on fistula prevalence among patients with a history of pelvic radiotherapy for prostate cancer., Materials and Methods: We queried PubMed, Embase, and Web of Science on October 7, 2020 for peer-reviewed publications pertaining to radiation-induced fistulas in the pelvis. For meta-analysis, we used the random-effects model. We used the I 2 statistic to quantify heterogeneity and the Newcastle-Ottawa Scale to assess risk of bias., Results: Our final meta-analysis included 6 cohort studies with a total of 7665 patients exposed to pelvic radiotherapy between 1967 and 2013. Median follow-up time was 35.5 months (IQR 33.5-57.5). Pooled prevalence of radiation-induced fistula across all 6 cohort studies was 0.2% (95% CI: 0.1-0.4, I 2  = 0.000%, P < .608). In subgroup analysis, we did not detect significant heterogeneity in fistula prevalence in patients who were re-irradiated (0.3%, 95% CI: 0.1-0.4; P = .762) or patients on concurrent chemotherapy (0.4%, 95% CI: -0.3 -1.2; P = .664) compared to those receiving their first course of radiotherapy alone. No randomized controlled trials met inclusion criteria due to ambiguous and inconsistent reporting language for fistula occurrence., Conclusion: There is limited published literature reporting fistula as an adverse event of prostate cancer radiotherapy, especially in the medium and long-term period. Patients undergoing pelvic radiotherapy for prostate cancer appear at low short-term risk for developing fistulas. Adverse event reporting in randomized controlled trials merits greater granularity where fistulas should be reported with specificity rather than aggregating into broad categories of genitourinary or gastrointestinal adverse events., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Hypofractionation is noninferior to conventional fractionation in the treatment of localized prostate cancer. Using results from the European Society of Radiation Oncology's (ESTRO) Global Impact of Radiotherapy in Oncology (GIRO) initiative survey on hypofractionation, this study identifies rates of adoption, facilitating factors, and barriers to adoption of hypofractionation in prostate cancer across World Bank income groups., Materials and Methods: The ESTRO-GIRO initiative administered an international, anonymous, electronic survey to radiation oncologists from 2018 to 2019. Physician demographics, clinical practice characteristics, and hypofractionation regimen use (if any) for several prostate cancer scenarios were collected. Responders were asked about specific justifications and barriers to adopting hypofractionation, and responses were stratified by World Bank income group. Multivariate logistic regression models were used to analyze variables associated with hypofractionation preference., Results: A total of 1,157 physician responses were included. Most respondents (60%) were from high-income countries (HICs). In the curative setting, hypofractionation was most often preferred in low- and intermediate-risk prostate cancers, with 52% and 47% of respondents reporting hypofractionation use in ≥50% of patients, respectively. These rates drop to 35% and 20% in high-risk prostate cancer and where pelvic irradiation is indicated. Most respondents (89%) preferred hypofractionation in the palliative setting. Overall, respondents from upper-middle-income countries and lower-middle- and low-income countries were significantly less likely to prefer hypofractionation than those from HICs ( P < .001). The most frequently cited justification and barrier were availability of published evidence and fear of worse late toxicity, respectively., Conclusion: Hypofractionation preference varies by indication and World Bank income group, with greater acceptance among providers in HICs for all indications. These results provide a basis for targeted interventions to increase provider acceptance of this treatment modality.

Purpose: This study aims to evaluate the outcomes and toxicities in patients with palpable local recurrence of prostate cancer after radical prostatectomy (RP), who were treated with salvage high dose-rate brachytherapy (HDR-BT) with or without pelvic external beam radiotherapy (EBRT)., Methods: This retrospective review included patients with palpable local recurrence of prostate cancer after RP who underwent salvage HDR-BT at a single institution between 2002 and 2020. HDR-BT regimens included 950 cGy x 2 (N = 4) or 1500 cGy x 1 (N = 2) combined with EBRT; or monotherapy with 950 cGy x 4 (N = 1) or 800 cGy x 2 (N = 1). Toxicity was graded according to CTCAE Version 5.0., Results: A total of 8 patients were included. Median follow-up was 49 months (range: 9-223 months). Median age at time of salvage brachytherapy was 68 years (range: 59-85 years). Seven out of 8 patients were alive at last follow-up. There have been no locoregional recurrences. Three patients developed distant metastatic disease. One patient developed acute grade 3 urinary obstruction requiring catheterization, which lasted for 1 day postbrachytherapy. One patient developed late grade 3 urinary incontinence 18 months after brachytherapy. There were no other grade 2+ toxicities., Conclusions: This study demonstrates the safety and efficacy of salvage HDR-BT in the setting of palpable local recurrence of prostate cancer after RP, with durable locoregional control and acceptable rates of toxicity. HDR-BT should be further explored as an option for dose-escalated salvage radiotherapy after prior radical prostatectomy., (Copyright © 2022 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Both the performance characteristics of prostate-specific membrane antigen positron emission tomography and insurance approval improves with increasing prostate-specific antigen (PSA) level causing some physicians to delay post-radical prostatectomy salvage radiation therapy (sRT) after PSA failure. Yet, it is unknown for men with at most one high-risk factor (ie, pT3/4 or prostatectomy [p] Gleason score 8-10) whether a PSA level exists above which initiating sRT is associated with increased all-cause mortality (ACM)-risk and was investigated., Methods: Using a multinational database of 25,551 patients with pT2-4N0 or NXM0 prostate cancer, multivariable Cox regression analysis evaluated whether an association with a significant increase in ACM-risk existed when sRT was delivered above a prespecified PSA level beginning at 0.10 ng/mL and in 0.05 increments up to 0.50 ng/mL versus at or below that level. The model was adjusted for age at and year of radical prostatectomy, established prostate cancer prognostic factors, institution, and the time-dependent use of androgen deprivation therapy., Results: After a median follow-up of 6.00 years, patients who received sRT at a PSA level >0.25 ng/mL had a significantly higher ACM-risk (AHR, 1.49; 95% CI, 1.11 to 2.00; P = .008) compared with men who received sRT when the PSA was ≤0.25 mg/mL. This elevated ACM-risk remained significant for all PSA cutpoints up to 0.50 ng/mL but was not significant at PSA cutpoint values below 0.25 ng/mL., Conclusion: Among patients with at most one high-risk factor, initiating sRT above a PSA level of 0.25 ng/mL was associated with increased ACM-risk.

Background: Radiopharmaceuticals, including Ga-68-prostate specific membrane antigen (PSMA)-11 and F-18-Fluciclovine, are increasingly used to inform therapies for prostate cancer (CaP). Stereotactic body radiation therapy (SBRT) to PET-detected oligometastatic CaP has been shown to improve progression free survival (PFS) and delay androgen deprivation therapy (ADT) compared to observation. For men who subsequently develop oligorecurrent CaP, outcomes following second SBRT are unknown., Methods: A retrospective cohort study was conducted. Eligibility criteria included patients with oligometastatic (1-5 lesions) CaP detected on PSMA or Fluciclovine PET who underwent 2 consecutive SBRT courses to tracer-avid sites. Data on stage, tracer type, concurrent systemic therapy, and prostate-specific antigen (PSA) responses for first SBRT (SBRT1) and second SBRT (SBRT2) were collected. Outcomes included PSA decline ≥50% (PSA50), PFS after SBRT2, and ADT initiation or intensification-free survival after SBRT2. Factors potentially associated with PSA50 after SBRT2 was evaluated with multivariable logistic regression. Factors potentially associated with PFS and ADT initiation/intensification-free survival after SBRT2 were evaluated with separate multivariable Cox proportional-hazards models., Results: Twenty-five patients were identified. At SBRT2, oligorecurrence was detected on PSMA and Fluciclovine PET in 17 (68%) and 8 (32%) patients, respectively. Fifteen (60%) patients had castration-sensitive disease and 10 (40%) had castration-resistant disease. After SBRT2, 16 (64%) achieved a PSA50 response, median PFS was 11.0mo, and median ADT initiation/intensification-free survival was 23.2mo. On multivariable analysis, maximum percent change in PSA after SBRT1 (OR 0.94, 95%CI 0.88-0.99, P = 0.046) and concurrent change in systemic therapy (OR 21.61, 95%CI 1.12-417.9, P = 0.042) were associated with PSA50 responses after SBRT2. PSA50 response after SBRT1 was associated with improved PFS (HR 0.36, 95%CI 0.00-0.42, P = 0.008) and ADT initiation/intensification-free survival (HR 0.07, 95%CI 0.01-0.68, P = 0.021) after SBRT2. From SBRT1 to last follow-up (median 48 months), 7 (28%) patients remained ADT-free., Conclusions: Serial SBRT for oligometastatic CaP detected on PSMA or Fluciclovine PET is feasible and can achieve PSA declines, with or without systemic therapy. Degree of biochemical response to first SBRT warrants further study as a potential predictor of PSA response, PFS, and ADT initiation/intensification-free survival following a subsequent SBRT course. This preliminary evidence provides rationale for larger, prospective studies of this strategy., Competing Interests: Conflict of interest The authors have no competing financial interests to report in relation to the work described., (Published by Elsevier Inc.)

Purpose: Hypofractionated breast radiotherapy has been found to be equivalent to conventional fractionation in many clinical trials. Using data from the European Society for Radiotherapy and Oncology Global Impact of Radiotherapy in Oncology survey, we identified preferences for hypofractionation in breast cancer across World Bank income groups and the perceived facilitators and barriers to its use., Materials and Methods: An international, electronic survey was administered to radiation oncologists from 2018 to 2019. Demographics, practice characteristics, preferred hypofractionation regimen for specific breast cancer scenarios, and facilitators and barriers to hypofractionation were reported and stratified by World Bank income groups. Variables associated with hypofractionation were assessed using multivariate logistic regression models., Results: One thousand four hundred thirty-four physicians responded: 890 (62%) from high-income countries (HICs), 361 (25%) from upper-middle-income countries (UMICs), 183 (13%) from low- and lower-middle-income countries (LLMICs). Hypofractionation was preferred most frequently in node-negative disease after breast-conserving surgery, with the strongest preference reported in HICs (78% from HICs, 54% from UMICs, and 51% from LLMICs, P < .001). Hypofractionation for node-positive disease postmastectomy was more frequently preferred in LLMICs (28% from HICs, 15% from UMICs, and 35% from LLMICs, P < .001). Curative doses of 2.1 to < 2.5 Gy in 15-16 fractions were most frequently reported, with limited preference for ultra-hypofractionation, but significant variability in palliative dosing. In adjusted analyses, UMICs were significantly less likely than LLMICs to prefer hypofractionation across all curative clinical scenarios, whereas respondents with > 1 million population catchments and with intensity-modulated radiotherapy were more likely to prefer hypofractionation. The most frequently cited facilitators and barriers were published evidence and fear of late toxicity, respectively., Conclusion: Preference for hypofractionation varied for curative indications, with greater acceptance in earlier-stage disease in HICs and in later-stage disease in LLMICs. Targeted educational interventions and greater inclusivity in radiation oncology clinical trials may support greater uptake.

Background: Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15-59 years across SSA., Methods: We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units., Results: We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group., Conclusions: As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA., (© 2022. The Author(s).)

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scans have higher sensitivity and specificity for detecting lymph nodes or metastatic disease relative to conventional imaging in prostate cancer staging. Since its FDA approval and incorporation into treatment guidelines, the use of PSMA PET has increased in patients undergoing initial staging, those with recurrence after initial definitive treatment, and patients with metastatic disease. Although the early detection of metastatic lesions is changing disease management, it is unclear whether this impact on management translates into clinical benefit. This review will summarize evidence pertaining to the change in patient management due to PSMA PET use and will discuss the implications of PSMA PET on treatment decisions in prostate cancer, particularly in the settings of biochemical recurrence and metachronous oligometastatic disease.

Purpose: Side effect profiles play an important role in treatment decisions for localized prostate cancer. Emergency department (ED) visits, which may be due to side effects from treatment, can be measured in real-world, structured, electronic health record (EHR) data. The goal of this study was to determine whether treatments for localized prostate cancer are associated with ED visits, as a measure of side effects, using EHR data., Methods and Materials: We used a self-controlled case series study design, including patients treated at an urban academic medical center with radiation therapy (RT) or radical prostatectomy (RP) for prostate cancer between 2011 and 2020 who had visits documented for ≥6 months before and after treatment and ≥1 ED visit. We estimated relative incidences (RI) of ED visits, comparing incidence in the exposed and unexposed periods, with the exposed period being between start of treatment and 1 month after completion, and the unexposed period consisting of all other documented time., Results: Among men who had at least 1 ED visit and after adjusting for age, there were higher rates of ED visits after RP (RI, 20.4; 95% confidence interval [CI], 15.4-27.0; P < .001), RT overall (RI, 2.4; CI, 1.7-3.4; P < .001), intensity modulated radiation therapy with high dose-rate brachytherapy (RI, 3.4; CI, 1.7-6.8; P < .001) or stereotactic body radiation therapy boost (RI, 7.1; CI, 3.4-14.8; P < .001), and high dose rate brachytherapy alone (RI, 16.3; CI, 7.2-36.9; P < .001) compared with unexposed time. The number needed to harm to result in an ED visit was less for RP (17; CI, 13-23) than RT overall (43; CI, 25-126), but varied by RT modality., Conclusions: In summary, relative rates of ED visits vary by treatment type, suggesting differing severities of side effects. These data may aid in selecting treatments and demonstrate the feasibility of using the self-controlled case series study design on ED visits in real-world, structured EHR data to better understand side effects of treatment., (Copyright © 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Radiation therapy is a possible treatment strategy for patients with testicular seminoma after orchiectomy in clinical stage I or II disease. Little is known about the outcome of patients who experience a relapse after radiation therapy., Methods and Materials: Data from 61 patients who relapsed after adjuvant or curative radiation therapy from 17 centers in 11 countries were collected and retrospectively analyzed. Primary outcomes were disease-free and overall survival. Secondary outcomes were time to relapse, stage at relapse, treatment for relapse, and rate of febrile neutropenia during chemotherapy for relapse., Results: With a median follow-up of 9.9 years (95% confidence interval [CI], 7.5-10.9), we found a 5-year disease-free survival of 90% (95% CI, 79-95) and a 5-year overall survival of 98% (95% CI, 89-100). Sixty-six percent of patients had stage III disease at time of relapse and 93% of patients fell into the good prognosis group per the International Germ Cell Cancer Collaborative Group classification. The median time to relapse after radiation therapy was 15.6 months (95% CI, 12-23). Twenty-two (36%) patients relapsed more than 2 years after radiation therapy and 7 (11.5%) patients relapsed more than 5 years after radiation therapy. One-third of relapses was detected owing to patients' symptoms, whereas two-thirds of relapses were detected during routine follow-up. The majority (93%) of cases were treated with cisplatin-based chemotherapy. The rate of febrile neutropenia during chemotherapy was 35%. Five patients experienced a second relapse. At last follow-up, 55 patients (90%) were alive without disease. Only 1 patient died owing to disease progression., Conclusions: Cisplatin-based chemotherapy for patients with seminoma who have relapsed after treatment with radiation therapy alone leads to excellent outcomes. Patients and physicians should be aware of possible late relapses after radiation therapy., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Prostate cancer is the most frequent cancer in men and a leading cause of cancer death. Determining a patient's optimal therapy is a challenge, where oncologists must select a therapy with the highest likelihood of success and the lowest likelihood of toxicity. International standards for prognostication rely on non-specific and semi-quantitative tools, commonly leading to over- and under-treatment. Tissue-based molecular biomarkers have attempted to address this, but most have limited validation in prospective randomized trials and expensive processing costs, posing substantial barriers to widespread adoption. There remains a significant need for accurate and scalable tools to support therapy personalization. Here we demonstrate prostate cancer therapy personalization by predicting long-term, clinically relevant outcomes using a multimodal deep learning architecture and train models using clinical data and digital histopathology from prostate biopsies. We train and validate models using five phase III randomized trials conducted across hundreds of clinical centers. Histopathological data was available for 5654 of 7764 randomized patients (71%) with a median follow-up of 11.4 years. Compared to the most common risk-stratification tool-risk groups developed by the National Cancer Center Network (NCCN)-our models have superior discriminatory performance across all endpoints, ranging from 9.2% to 14.6% relative improvement in a held-out validation set. This artificial intelligence-based tool improves prognostication over standard tools and allows oncologists to computationally predict the likeliest outcomes of specific patients to determine optimal treatment. Outfitted with digital scanners and internet access, any clinic could offer such capabilities, enabling global access to therapy personalization., (© 2022. The Author(s).)

Purpose: Radiation dose intensification improves outcome in men with high-risk prostate cancer (HR-PCa). A prospective trial was conducted to determine safety, feasibility, and maximal tolerated dose of multilevel magnetic resonance imaging (MRI)-based 5-fraction SABR in patients with HR-PCa., Methods and Materials: This phase I clinical trial enrolled patients with HR-PCa with grade group ≥4, prostate-specific antigen (PSA) ≥20 ng/mL, or radiographic ≥T3, and well-defined prostatic lesions on multiparametric MRI (mpMRI) into 4 dose-escalation cohorts. The initial cohort received 47.5 Gy to the prostate, 50 Gy to mpMRI-defined intraprostatic lesion(s), and 22.5 Gy to pelvic lymph nodes in 5 fractions. Radiation doses were escalated for pelvic nodes to 25 Gy and mpMRI lesion(s) to 52.5 Gy and then 55 Gy. Escalation was performed sequentially according to rule-based trial design with 7 to 15 patients per cohort and a 90-day observation period. All men received peri-rectal hydrogel spacer, intraprostatic fiducial placement, and 2 years of androgen deprivation. The primary endpoint was maximal tolerated dose according to a 90-day acute dose-limiting toxicity (DLT) rate <33%. DLT was defined as National Cancer Institute Common Toxicity Criteria for Adverse Events ≥grade 3 treatment-related toxicity. Secondary outcomes included acute and delayed gastrointestinal (GI)/genitourinary (GU) toxicity graded with Common Toxicity Criteria for Adverse Events., Results: Fifty-five of the 62 enrolled patients were included in the analysis. Dose was escalated through all 4 cohorts without observing any DLTs. Median overall follow-up was 18 months, with a median follow-up of 42, 24, 12, and 7.5 months for cohorts 1 to 4 respectively. Acute and late grade 2 GU toxicities were 25% and 20%, while GI were 13% and 7%, respectively. Late grade 3 GU and GI toxicities were 2% and 0%, respectively., Conclusions: SABR dose for HR-PCa was safely escalated with multilevel dose painting of 47.5 Gy to prostate, 55 Gy to mpMRI-defined intraprostatic lesions, and 25 Gy to pelvic nodal region in 5 fractions. Longer and ongoing follow-up will be required to assess late toxicity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: To evaluate acute and late genitourinary and gastrointestinal toxicities and patient reported urinary and sexual function following accelerated, hypofractionated external beam radiotherapy to the prostate, seminal vesicles and pelvic lymph nodes and high dose rate (HDR) brachytherapy or stereotactic body radiation therapy (SBRT) prostate boost., Methods: Patients at a single institution with NCCN intermediate- and high-risk localized prostate cancer with logistical barriers to completing five weeks of whole pelvic radiotherapy (WPRT) were retrospectively reviewed for toxicity following accelerated, hypofractionated WPRT (41.25 Gy in 15 fractions of 2.75 Gy). Patients also received prostate boost radiotherapy with either HDR brachytherapy (1 fraction of 15 Gy) or SBRT (19 Gy in 2 fractions of 9.5 Gy). The duration of androgen deprivation therapy was at the discretion of the treating radiation oncologist. Toxicity was evaluated by NCI CTCAE v 5.0., Results: Between 2015 and 2017, 22 patients with a median age of 71 years completed accelerated, hypofractionated WPRT. Median follow-up from the end of radiotherapy was 32 months (range 2-57). 5%, 73%, and 23% of patients had clinical T1, T2, and T3 disease, respectively. 86% of tumors were Gleason grade 7 and 14% were Gleason grade 9. 68% and 32% of patients had NCCN intermediate- and high-risk disease, respectively. 91% and 9% of patients received HDR brachytherapy and SBRT prostate boost following WPRT, respectively. Crude rates of grade 2 or higher GI and GU toxicities were 23% and 23%, respectively. 3 patients (14%) had late or persistent grade 2 toxicities of urinary frequency and 1 patient (5%) had late or persistent GI toxicity of diarrhea. No patient experienced grade 3 or higher toxicity at any time. No difference in patient-reported urinary or sexual function was noted at 12 months., Conclusions: Accelerated, hypofractionated whole pelvis radiotherapy was associated with acceptable GU and GI toxicities and should be further validated for those at risk for harboring occult nodal disease., (© 2022. The Author(s).)

The European Association of Urology (EAU) prostate cancer guidelines panel recommends risk groups for biochemical recurrence (BCR) of prostate cancer to identify men at high risk of progression or metastatic disease. The rapidly growing availability of PSMA-directed PET imaging will impact prostate cancer staging. We determined the rates of local and metastatic disease in BCR and biochemical persistence (BCP) of prostate cancer stratified by EAU BCR risk groups and BCP. Methods: Patients with BCR or BCP were enrolled under the same prospective clinical trial protocol conducted at 3 sites ( n  = 1,777 [91%]: UCLA, n  = 662 [NCT02940262]; University of California San Francisco, n  = 508 [NCT03353740]; University of Michigan, n  = 607 [NCT03396874]); 183 patients with BCP from the Universities of Essen, Bologna, and Munich were included retrospectively. Patients with BCR had to have sufficient data to determine the EAU risk score. Multivariate, binomial logistic regression models were applied to assess independent predictors of M1 disease. Results: In total, 1,960 patients were included. Post-radical prostatectomy EAU BCR low-risk, EAU BCR high-risk, and BCP groups yielded distant metastatic (M1) detection in 43 of 176 (24%), 342 of 931 (37%), and 154 of 386 (40%) patients. For postradiotherapy EAU BCR low-risk and EAU BCR high-risk groups, the M1 detection rate was 113 of 309 (37%) and 110 of 158 (70%), respectively. BCP, high-risk BCR, and higher levels of serum prostate-specific antigen were significantly associated with PSMA PET M1 disease in multivariate regression analysis. PSMA PET revealed no disease in 25% and locoregional-only disease in 33% of patients with post-radical prostatectomy or postradiotherapy EAU BCR high risk. Conclusion: Our findings support the new EAU classification; EAU BCR high-risk groups have higher rates of metastatic disease on PSMA PET than do the low-risk groups. Discordant subgroups, including metastatic disease in low-risk patients and no disease in high-risk patients, warrant inclusion of PSMA PET stage to refine risk assessment., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: This phase II clinical trial evaluated whether the addition of stereotactic ablative radiotherapy (SAbR), which may promote tumor antigen presentation, improves the overall response rate (ORR) to high-dose IL2 (HD IL2) in metastatic renal cell carcinoma (mRCC)., Patients and Methods: Patients with pathologic evidence of clear cell renal cell carcinoma (RCC) and radiographic evidence of metastasis were enrolled in this single-arm trial and were treated with SAbR, followed by HD IL2. ORR was assessed based on nonirradiated metastases. Secondary endpoints included overall survival (OS), progression-free survival (PFS), toxicity, and treatment-related tumor-specific immune response. Correlative studies involved whole-exome and transcriptome sequencing, T-cell receptor sequencing, cytokine analysis, and mass cytometry on patient samples., Results: Thirty ethnically diverse mRCC patients were enrolled. A median of two metastases were treated with SAbR. Among 25 patients evaluable by RECIST v1.1, ORR was 16% with 8% complete responses. Median OS was 37 months. Treatment-related adverse events (AE) included 22 grade ≥3 events that were not dissimilar from HD IL2 alone. There were no grade 5 AEs. A correlation was observed between SAbR to lung metastases and improved PFS ( P = 0.0165). Clinical benefit correlated with frameshift mutational load, mast cell tumor infiltration, decreased circulating tumor-associated T-cell clones, and T-cell clonal expansion. Higher regulatory/CD8 + T-cell ratios at baseline in the tumor and periphery correlated with no clinical benefit., Conclusions: Adding SAbR did not improve the response rate to HD IL2 in patients with mRCC in this study. Tissue analyses suggest a possible correlation between frameshift mutation load as well as tumor immune infiltrates and clinical outcomes., (©2021 American Association for Cancer Research.)

Purpose: To provide a comprehensive analysis of radiation oncology (RO) fellowship growth from 2010 to 2020., Methods and Materials: A collated database of RO fellowship programs and matriculants was created using (1) RO residency program (n = 92) and graduate (n = 2082) web searches, (2) prospective American Society for Radiation Oncology (ASTRO) Career Center postings database, (3) Association of Residents in Radiation Oncology Fellowship Directory, (4) RO fellowship survey data, (5) ASTRO Membership Directory, and (6) direct e-mail contact with fellowship program directors. Linear regression was used to assess the statistical significance of RO fellowship program, position, and matriculant growth over time., Results: From 2010 to 2020, the number of RO fellowship programs and annual positions significantly increased from 20 to 37 (1.60 increase per year; 95% confidence interval, 1.32-1.89; P < .001) and 20 to 39 (1.81 increase per year; 95% confidence interval, 1.52-2.10; P < .001), respectively. The most commonly offered fellowship disciplines were proton therapy (n = 10), brachytherapy (n = 7), stereotactic radiosurgery/stereotactic body radiation therapy (n = 6), general RO (n = 5), and customizable to trainees' interests (n = 3). Only 10 (27%) fellowships had a formal curriculum. All fellowships were unaccredited. Four (10.8%) programs were offered at institutions without an Accreditation Council for Graduate Medical Education-accredited RO residency training program, all established within the past 2 years. In addition, 54.8% (171 of 312) of available fellowship positions were filled between 2010 to 2020. Of these, 94 (55.0%) were graduates of US RO residency programs. The mean number of total fellows and US-residency trained fellows per year was 15 (range, 5-23) and 8 (range, 2-20), respectively. There was no significant increase in the number of annual matriculated fellows over time (P = .077). Among US-residency trained fellows, 27 (28.7%), 37 (39.4%), and 29 (30.9%) were from small (≤6), medium (7-12), and large (>12) residency programs, respectively. Twenty-eight (29.8%), 13 (13.8%), 25 (26.6%), and 27 (28.7%) trained in the Northeast, Midwest, South, and West, respectively., Conclusions: There has been significant growth in unaccredited RO fellowship programs and annual positions during the past decade, although the number of matriculants has remained stable. We report for the first time the recent establishment of fellowships at institutions without an Accreditation Council for Graduate Medical Education-accredited RO residency program. The impact of fellowship programs on the training of RO residents should be studied., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Biology has become a prime area for the deployment of deep learning and artificial intelligence (AI), enabled largely by the massive data sets that the field can generate. Key to most AI tasks is the availability of a sufficiently large, labeled data set with which to train AI models. In the context of microscopy, it is easy to generate image data sets containing millions of cells and structures. However, it is challenging to obtain large-scale high-quality annotations for AI models. Here, we present HALS (Human-Augmenting Labeling System), a human-in-the-loop data labeling AI, which begins uninitialized and learns annotations from a human, in real-time. Using a multi-part AI composed of three deep learning models, HALS learns from just a few examples and immediately decreases the workload of the annotator, while increasing the quality of their annotations. Using a highly repetitive use-case-annotating cell types-and running experiments with seven pathologists-experts at the microscopic analysis of biological specimens-we demonstrate a manual work reduction of 90.60%, and an average data-quality boost of 4.34%, measured across four use-cases and two tissue stain types., (© 2021. The Author(s).)

Purpose: To evaluate the feasibility, safety, oncologic outcomes, and immune effect of neoadjuvant stereotactic radiation (Neo-SAbR) followed by radical nephrectomy and thrombectomy (RN-IVCT)., Methods and Materials: These are results from the safety lead-in portion of a single-arm phase 1 and 2 trial. Patients with kidney cancer (renal cell carcinoma [RCC]) and inferior vena cava (IVC) tumor thrombus (TT) underwent Neo-SAbR (40 Gy in 5 fractions) to the IVC-TT followed by open RN-IVCT. Absence of grade 4 to 5 adverse events (AEs) within 90 days of RN-IVCT was the primary endpoint. Exploratory studies included pathologic and immunologic alterations attributable to SAbR., Results: Six patients were included in the final analysis. No grade 4 to 5 AEs were observed. A total of 81 AEs were reported within 90 days of surgery: 73% (59/81) were grade 1, 23% (19/81) were grade 2, and 4% (3/81) were grade 3. After a median follow-up of 24 months, all patients are alive. One patient developed de novo metastatic disease. Of 3 patients with metastasis at diagnosis, 1 had a complete and another had a partial abscopal response without the concurrent use of systemic therapy. Neo-SABR led to decreased Ki-67 and increased PD-L1 expression in the IVC-TT. Inflammatory cytokines and autoantibody titers reflecting better host immune status were observed in patients with nonprogressive disease., Conclusions: Neo-SAbR followed by RN-IVCT for RCC IVC-TT is feasible and safe. Favorable host immune environment correlated with abscopal response to SABR and RCC relapse-free survival, though direct causal relation to SABR has yet to be established., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Adjuvant compared with early salvage radiation therapy (sRT) following radical prostatectomy (RP) has not been shown to reduce progression-free survival in randomized controlled trials. However, these trials might have missed a benefit in men with adverse pathology at RP given that these men were under-represented and immortal time bias might have been present; herein, we investigate this possibility., Methods: We evaluated the impact of adjuvant versus early sRT on all-cause mortality (ACM) risk in men with adverse pathology defined as positive pelvic lymph nodes (pN1) or pGleason score 8-10 prostate cancer (PC) and disease extending beyond the prostate (pT3/4). We used a treatment propensity score to minimize potential treatment selection bias when estimating the causal effect of adjuvant versus early sRT on ACM risk and a sensitivity analysis to assess the impact that varying definitions of adverse pathology had on ACM risk adjusting for age at RP, PC prognostic factors, site, and the time-dependent use of post-RP androgen deprivation therapy., Results: After a median follow-up (interquartile range) of 8.16 (6.00-12.10) years, of the 26,118 men in the study cohort, 2,104 (8.06%) died, of which 539 (25.62%) were from PC. After excluding men with a persistent prostate-specific antigen, adjuvant compared with early sRT was associated with a significantly lower ACM risk among men with adverse pathology at RP when men with pN1 PC were excluded (0.33 [0.13-0.85]; P = .02) or included (0.66 [0.44-0.99]; P = .04)., Conclusion: Adjuvant radiation therapy should be considered in men with pN1 or pGleason score 8 to 10 and pT3/4 PC given the possibility that a significant reduction in ACM risk exists., Competing Interests: Derya TilkiHonoraria: Janssen, Ipsen, Exact SciencesConsulting or Advisory Role: Tolero Pharmaceuticals, miR ScientificResearch Funding: JanssenTravel, Accommodations, Expenses: Tolero Pharmaceuticals Markus GraefenHonoraria: Astellas Pharma, Bayer, Takeda, Janssen, MedtronicConsulting or Advisory Role: MedtronicTravel, Accommodations, Expenses: Astellas Pharma, Bayer, Janssen, Takeda Thomas WiegelHonoraria: Janssen-Cilag, IpsenConsulting or Advisory Role: Janssen-CilagSpeakers' Bureau: Ipsen Dirk BöhmerResearch Funding: Ferring Osama MohamadResearch Funding: Salesforce Janet E. CowanStock and Other Ownership Interests: GlaxoSmithKline, McKesson Felix Y. FengLeadership: PFS GenomicsStock and Other Ownership Interests: PFS GenomicsHonoraria: GenentechConsulting or Advisory Role: Blue Earth Diagnostics, Celgene, Janssen Biotech, Genentech, Myovant Sciences, Roivant, Astellas Pharma, SerImmuneResearch Funding: Zenith EpigeneticsPatents, Royalties, Other Intellectual Property: I helped develop a molecular signature to predict radiation resistance in breast cancer, and this signature was patented by the University of Michigan, my employer. It is in the process of being licensed to PFS Genomics, which is a company that I co-founded Peter R. CarrollStock and Other Ownership Interests: Nutcracker Therapeutics IncConsulting or Advisory Role: Nutcracker Therapeutics Inc, Insightec, Progenics, Francis Medical Bruce J. TrockConsulting or Advisory Role: GenomeDx, Myriad GeneticsResearch Funding: Myriad Genetics, MDxHealth Alan W. PartinHonoraria: International Prostate Cancer UpdateNo other potential conflicts of interest were reported.

Background and Objectives: With global efforts to develop and deliver a COVID-19 vaccine rapidly, vaccine hesitancy stands as a barrier to these efforts. We aimed to estimate the proportion of Syrian adult population intending to be vaccinated against COVID-19 and, principally, to assess the demographic and attitudinal factors associated with it in order to approach suitable solutions., Methods: An anonymous online questionnaire was conducted between 23rd December 2020 and 5th January 2021 in various provinces in Syria. A total of 3402 adults were sampled to reflect the population demographic factors. Attitudinal factors included Covid-19 fears, risks, and beliefs on the origin. Vaccination hesitancy and knowledge were also measured. The intention to get vaccinated against COVID-19 was the primary endpoint., Results: According to their statements, 1222 participants (35.92%) will consent to get vaccinated against COVID-19. Our findings indicate that male gender, younger age, rural residence, not having children, smoking, fear about COVID-19, individual perceived severity, believing in the natural origin of the coronavirus, and high vaccination knowledge were positive predictors of embracing COVID-19 vaccine when it is available., Conclusion: COVID-19 vaccine acceptance rate is considerably poor across Syrian population compared to populations in developed countries. Vaccine hesitancy is closely bound to the fear of side effects and doubts about vaccine efficacy. Factors such as conspiracy beliefs and myths about the vaccine lower vaccine uptake. Thus, interventional educational campaigns are increasingly required to overcome misinformation and avert low vaccination acceptance rates.