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The study was carried out using ten maize hybrids in spring 2015 and 2016 were planted at the field of Agriculture College, University of Duhok. All treatments arranged in Randomized Complete Block Design (RCBD) with three replications to determine the heritability, genetic advance, correlation and genetic parameters govering the inheritance of grain yield and related agronomic traits. The result showed significant difference among hybrids for studied traits in spring 2015 and 2016 and also the results revealed that hybrids and seasons interaction had a significant difference for all traits. The season’s spring 2015 was superior than spring 2016 in leaf area, days to 75% tasseling and silking, yield and its components. The hybrid (OH40 xIK8) was superior in No. of rows ear-1, No. of kernels row-1,300 kernel weight and kernel yield plant1. All studied traits recorded higher value of heritability, high genetic advance coupled with heritability was observed in leaf area and kernel yield plant-1, thus selection based on these traits will be effective in maize breeding program. Grain yield was positively correlated with leaf area and 300 kernel weight, also No. of row ear-1 exhibited positive correlation coefficient with leaf area, 300-kernell weight and kernel yield plant-1.

Background: Hydatid disease is widespread and considered endemic in the Middle East and the Mediterranean, Iraq is one of the countries with a high endemicity of this disease. Objectives: The aim of this study is to diagnose hydatidosis and to identify the prevalence in human and animals in two different areas Sulaimaniya governorate which include Sulaimaniya city and Saedsadq district., Methods: Seroepidemiological survey was conducted by using enzyme-linked immunosorbent assay (ELISA) and Indirect Haemagglutination IHA to detect anti Echinococcus granulosus antibody in random blood samples (536) of different sex, ages, and occupation out patients, in Sulaimaniya and Saedsadq. In the animal study inspection and examination of the internal organs (liver, lungs, spleen and heart) Results: The Seropositivty in Saedsadq was higher( 3.7% )than in Sulaimaniya( 2.5%), and in female (2.8%, 6.4%) were higher than in male (1.6%, 1.2%) respectively both in Sulaimaniya and Saedsadq. In animal study results revealed that In Sulaimaniya infection rates were (1.5% of sheep, 0.5% of goats and 0.2% of cattle), less than in Saedsadq (7.5%, 2.8% and 1.7%) respectively, Conclusion: The seropositive was higher in Saedsadq than Sulaimaniya , and higher among females than males in all age groups. The prevalence and fertility of hydatid cysts in sheep is higher than goat and cattle, sheep. Liver is the main involved organ.

Glucose-6-phosphate dehydrogenase deficiency (G6PDd) is the most common enzymopathy globally, and deficient individuals may experience severe hemolysis following treatment with 8-aminoquinolines. With increasing evidence of Plasmodium vivax infections throughout sub-Saharan Africa, there is a pressing need for population-level data at on the prevalence of G6PDd. Such evidence-based data will guide the expansion of primaquine and potentially tafenoquine for radical cure of P. vivax infections. This study aimed to quantify G6PDd prevalence in two geographically distinct areas in Sudan, and evaluating the performance of a qualitative CareStart rapid diagnostic test as a point-of-care test. Blood samples were analyzed from 491 unrelated healthy persons in two malaria-endemic sites in eastern and central Sudan. A pre-structured questionnaire was used which included demographic data, risk factors and treatment history. G6PD levels were measured using spectrophotometry (SPINREACT) and first-generation qualitative CareStart rapid tests. G6PD variants (202 G>A; 376 A>G) were determined by PCR/RFLP, with a subset confirmed by Sanger sequencing. The prevalence of G6PDd by spectrophotometry was 5.5% (27/491; at 30% of adjusted male median, AMM); 27.3% (134/491; at 70% of AMM); and 13.1% (64/490) by qualitative CareStart rapid diagnostic test. The first-generation CareStart rapid diagnostic test had an overall sensitivity of 81.5% (95%CI: 61.9 to 93.7) and negative predictive value of 98.8% (97.3 to 99.6). All persons genotyped across both study sites were wild type for the G6PD G202 variant. For G6PD A376G all participants in New Halfa had wild type AA (100%), while in Khartoum the AA polymorphism was found in 90.7%; AG in 2.5%; and GG in 6.8%. Phenotypic G6PD B was detected in 100% of tested participants in New Halfa while in Khartoum, the phenotypes observed were B (96.2%), A (2.8%), and AB (1%). The African A- phenotype was not detected in this study population. Overall, G6PDd prevalence in Sudan is low-to-moderate but highly heterogeneous. Point-of-care testing with the qualitative CareStart rapid diagnostic test demonstrated moderate performance with moderate sensitivity and specificity but high negative predicative value. The two sites harbored primarily the African B phenotype. A country-wide survey is recommended to understand GP6PD deficiencies more comprehensively in Sudan. Author summary Malaria is caused by five species of parasites; of these Plasmodium falciparum and P. vivax cause the majority of global morbidity and mortality. Plasmodium vivax infection is an emerging public health problem in sub-Saharan Africa, including Sudan. Primaquine and other 8-aminoquinolines including tafenoquine are the primary treatments to target the silent liver stage (hypnozoites) in P. vivax infections. However, these regimens can cause severe intravascular hemolysis in patients suffering from glucose-6-phosphate dehydrogenase deficiency (G6PDd). To support safe and efficacious use of primaquine, and potentially tafenoquine in Sudan, this study aimed to estimate the prevalence of G6PDd across two sites in Sudan using spectrophotometry and a qualitative CareStart rapid diagnostic test. Subsequent genetic analysis by PCR/RFLP and sequencing of G6PD genetic variants was performed. This survey found an overall prevalence was 5.5% (27/491; 30% of adjusted male median, AMM), and 27.3% (134/491; 70% of AMM) and 13.1% (64/490) by qualitative CareStart rapid diagnostic test. Important differences in distribution of genetic variants of G6PD were found across the two sites, and the African A- was not observed. In univariate analysis a few parameters showed significant association with G6PD deficiency. In conclusion the prevalence of G6PDd was low to moderate but heterogonous, and the first-generation qualitative CareStart rapid diagnostic test showed moderate performance in both males and females.

Background: We performed an exploratory analysis of the SPARTAN trial to determine whether concomitant exposure to several classes of commonly prescribed medications influenced the effect of apalutamide on overall survival (OS) and metastasis-free survival (MFS) in patients with non-metastatic castration-resistant prostate cancer (nmCRPC)., Patients and Methods: SPARTAN was a phase III randomized controlled trial in which nmCRPC patients were randomly assigned in a 2:1 ratio to receive androgen deprivation therapy with or without apalutamide. We focused on 5 commonly prescribed classes of medications: metformin, statins, angiotensin converting enzyme inhibitors (ACEI), acetylsalicylic acid (ASA), and proton pump inhibitors (PPI) based on a plausible biological and clinical rationale. To determine the potential effect modification, we applied multivariable Cox regression models for OS and MFS separately with additional interaction terms. To determine the independent association of concomitant medications with OS and MFS, we used IPTW-based log-rank test. A 2-sided p < 0.01 was considered statistically significant., Results: We did not find statistically significant differences in effect from apalutamide on OS across subgroups stratified by concomitant exposure to any of the medication classes. While there was some difference in the treatment effect from apalutamide on MFS between patients with concomitant statins (adjusted hazard ratio [aHR]: 0.20; 95 % CI: 0.15-0.28) versus without concomitant statins (aHR: 0.31 [0.24-0.39]), this did not reach the pre-specified threshold of statistical significance (p = 0.011). On IPTW-based analysis, patients treated concomitantly with metformin (median: not reached versus 31 months; p = 0.002), or ACEI (median: 37 versus 29 months, p = 0.006) had significantly improved MFS., Conclusions: In this post-hoc exploratory analysis of SPARTAN, effects of apalutamide on MFS and OS were consistent across subgroups stratified by exposure to concomitant medications. Exposure to concomitant metformin and ACEI was independently associated with a significant improvement in MFS., Competing Interests: Declaration of Competing Interest Dr. Roy reports Young Investigator Award from the Prostate Cancer Foundation which funded this research. In addition, Dr. Roy reports research grant from Swim Across America and honorarium from Varian. Dr. Spratt reports personal fees from Blue Earth, personal fees from Janssen, personal fees from AstraZeneca, Gammatile, Varian, and Boston Scientific, outside the submitted work. Dr. Kishan reported receiving personal fees from ViewRay, Inc, Varian Medical Systems, and Boston Scientific; receiving speaking honoraria, consulting fees, and research support from Varian Medical Systems, ViewRay, Inc, and Intelligent Automation; receiving grants from Janssen and Point Biopharma; and receiving research funding from ViewRay, Inc, outside the submitted work. Dr. Agarwal reports consulting or advisory roles for Pfizer, Medivation/Astellas, Bristol Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, Merck, Novartis, Eisai, Seagen, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, Gilead Sciences and research funding from Bayer, Bristol Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, crispr therapeutics, and Arvinas. Dr. Chowdhury, receiving honoraria, fees for serving on a speaker’s bureau, consulting fees, and travel support from Johnson and Johnson, Astellas Pharma, and Sanofi and grant support, honoraria, fees for serving on a speaker’s bureau, consulting fees, and travel support from Clovis Oncology. Dr. Jia reports personal fees from Blue Earth, and Myovant. Dr. Ong reports personal fees from Janssen, Bayer, AstraZeneca, and Pfizer. Dr. Morgan reports personal fees from Astellas, Bayer, Janssen, and TerSera and a research grant (institutional) from Knight Therapeutics, outside the submitted work. Dr. Swami reports consultancy to Astellas, Exelixis, Seattle Genetics, Imvax, Sanofi, Pfizer, AstraZeneca and Gilead and research funding to institute from Janssen, Exelixis and Astellas/Seattle Genetics. Dr. Saad reports grants, personal fees, and non-financial support from Janssen, during the conduct of the study; grants, personal fees, and non-financial support from Astellas, grants, personal fees, and non-financial support from Bayer, outside the submitted work. Dr. Wallis has received honoraria from AbbVie, Astellas, Astra Zeneca, Bayer, EMD Serono, Knight Therapeutics, Merck, Haymarket Media, Science & Medicine Canada, TerSera Canada, and Tolmar Pharmaceuticals Canada; reports consulting fees from Janssen Oncology, SESEN Bio, and Precision Point Specialty LLC; and has received research funding from Knight Therapeutics and Tolmar Pharmaceuticals, outside the submitted work. Dr. Malone has received honoraria from Astellas, Bayer, Janssen, and Sanofi; and travel and accommodations support from TerSera and Sanofi. There are no other conflicts of interest among the other authors., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Though several nomograms exist, machine learning (ML) approaches might improve prediction of pathologic stage in patients with prostate cancer. To develop ML models to predict pathologic stage that outperform existing nomograms that use readily available clinicopathologic variables., Methods: Patients with prostate adenocarcinoma who underwent surgery were identified in the National Cancer Database. Seven ML models were trained to predict organ-confined (OC) disease, extracapsular extension, seminal vesicle invasion (SVI), and lymph node involvement (LNI). Model performance was measured using area under the curve (AUC) on a holdout testing data set. Clinical utility was evaluated using decision curve analysis (DCA). Performance metrics were confirmed on an external validation data set., Results: The ML-based extreme gradient boosted trees model achieved the best performance with an AUC of 0.744, 0.749, 0.816, 0.811 for the OC, ECE, SVI, and LNI models, respectively. The MSK nomograms achieved an AUC of 0.708, 0.742, 0.806, 0.802 for the OC, ECE, SVI, and LNI models, respectively. These models also performed the best on DCA. Findings were consistent on both a holdout internal validation data set as well as an external validation data set., Conclusions: Our ML models better predicted pathologic stage relative to existing nomograms at predicting pathologic stage. Accurate prediction of pathologic stage can help oncologists and patients determine optimal definitive treatment options for patients with prostate cancer., (© 2024 Wiley Periodicals LLC.)

Purpose: Although recent technological advances in radiation therapy have significantly improved treatment outcomes, the global distribution of radiation therapy is unbalanced, making access especially challenging for patients in rural or low-resource settings because of travel burden. This systematic review aimed to explore the impact of geographic distance to treatment facilities on survival, as well as other treatment outcomes, among patients undergoing radiation therapy., Methods and Materials: A search of four databases (PubMed, Embase, CINAHL, and Web of Science) was performed. Studies were included if they were primary literature, published between May 2000 and May 2023, and reported the travel distances for patients undergoing radiation therapy for malignant conditions and its influence on survival outcomes. Studies were excluded if they did not report primary outcomes, were published before 2000, or were non-English., Results: After review, 23 studies were included. Most studies were conducted in the United States, with cervical cancer being the most frequently studied disease site. Data suggested that travel distances vary significantly, with patients often traveling a median distance of 20 miles to radiation therapy. Among the studies, 5 reported a negative impact on overall survival, often associating greater travel with nonadherence to recommended care. Other survival metrics, including progression-free survival and all-cause mortality, were also assessed, demonstrating similar variability in relation to travel distance. Conversely, seven studies found no significant impact on overall survival, and four suggested a positive impact on overall survival, with improved outcomes at centers with higher case volumes. Some data also revealed an inverse correlation between travel distance and the likelihood of receiving guideline-concordant radiation therapy., Conclusions: The impact of travel distance on radiation therapy outcomes is varied. Our findings underscore the challenges posed by travel in accessing radiation therapy and the disparities affecting particular patient demographic groups. Additional studies are needed to thoroughly assess the impacts of geographic disparities and to identify effective measures to address these challenges., (© 2024 The Authors.)

Purpose: Current clinical risk stratification methods for localized prostate cancer are suboptimal, leading to over- and undertreatment. Recently, machine learning approaches using digital histopathology have shown superior prognostic ability in phase III trials. This study aims to develop a clinically usable risk grouping system using multimodal artificial intelligence (MMAI) models that outperform current National Comprehensive Cancer Network (NCCN) risk groups., Materials and Methods: The cohort comprised 9,787 patients with localized prostate cancer from eight NRG Oncology randomized phase III trials, treated with radiation therapy, androgen deprivation therapy, and/or chemotherapy. Locked MMAI models, which used digital histopathology images and clinical data, were applied to each patient. Expert consensus on cut points defined low-, intermediate-, and high-risk groups on the basis of 10-year distant metastasis rates of 3% and 10%, respectively. The MMAI's reclassification and prognostic performance were compared with the three-tier NCCN risk groups., Results: The median follow-up for censored patients was 7.9 years. According to NCCN risk categories, 30.4% of patients were low-risk, 25.5% intermediate-risk, and 44.1% high-risk. The MMAI risk classification identified 43.5% of patients as low-risk, 34.6% as intermediate-risk, and 21.8% as high-risk. MMAI reclassified 1,039 (42.0%) patients initially categorized by NCCN. Despite the MMAI low-risk group being larger than the NCCN low-risk group, the 10-year metastasis risks were comparable: 1.7% (95% CI, 0.2 to 3.2) for NCCN and 3.2% (95% CI, 1.7 to 4.7) for MMAI. The overall 10-year metastasis risk for NCCN high-risk patients was 16.6%, with MMAI further stratifying this group into low-, intermediate-, and high-risk, showing metastasis rates of 3.4%, 8.2%, and 26.3%, respectively., Conclusion: The MMAI risk grouping system expands the population of men identified as having low metastatic risk and accurately pinpoints a high-risk subset with elevated metastasis rates. This approach aims to prevent both overtreatment and undertreatment in localized prostate cancer, facilitating shared decision making.

Importance: Preclinical studies suggest that exposure to prostate-directed local therapy (LT) may influence the efficacy of subsequent systemic therapy including androgen receptor pathway inhibitors. However, there is insufficient clinical evidence to support this premise in patients with nonmetastatic castrate-resistant prostate cancer (nmCRPC)., Objective: To determine whether exposure to prior prostate-directed LT (radical prostatectomy [RP], radiation therapy [RT], or both) played any effect-modifying role in the treatment effect of apalutamide on metastasis-free survival (MFS) and overall survival (OS) in patients with nmCRPC., Design, Setting, and Participants: This post hoc secondary analysis used individual patient data from SPARTAN (Study of Apalutamide [ARN-509] in Men With Non-Metastatic Castration-Resistant Prostate Cancer), a phase 3, double-blinded, placebo-controlled randomized clinical trial conducted at 332 sites in 26 countries. Between October 14, 2013, and December 15, 2016, patients with nmCRPC and a prostate-specific antigen doubling time of 10 months or less were randomly assigned to apalutamide vs placebo; all patients received androgen deprivation therapy. The final data analysis was performed on December 31, 2023., Exposure: Prior prostate-directed LT., Main Outcomes and Measures: Separate Cox proportional hazards regression models were constructed for OS and MFS, which included prior LT, treatment group, and an interaction term, in addition to a minimally sufficient set of confounders. Adjusted hazard ratios (HRs) with 95% CIs for MFS and OS were determined for the apalutamide groups with or without prior LT., Results: Among the 1179 evaluable patients included in this analysis, 795 received prior LT and 384 did not. The median age of patients with and without prior LT was 70 (IQR, 45-90) years and 75 (IQR, 50-95) years, respectively. The median follow-up was 52.0 (IQR, 51.5-52.8) months. A differential treatment effect of apalutamide on MFS was observed between patients with and without prior LT (P for interaction = .009), with greater benefits for those with prior LT (adjusted HR, 0.22 [95% CI, 0.17-0.27]) compared with those without prior LT (adjusted HR, 0.35 [95% CI, 0.25-0.51]). However, there was insufficient evidence of a differential treatment effect on OS among subgroups stratified by exposure to prior LT (P for interaction = .23), with improved OS in the subgroup with prior LT (adjusted HR, 0.72 [95% CI, 0.57-0.92]) but no significant difference in OS in the subgroup without prior LT (adjusted HR, 0.92 [95% CI, 0.64-1.31])., Conclusions and Relevance: This post hoc analysis of the SPARTAN trial provides evidence of an interaction between prior LT and apalutamide in patients with nmCRPC, with a clinically significant and more favorable treatment effect from apalutamide on MFS among patients with prior LT. Further studies are needed to validate these findings., Trial Registration: ClinicalTrials.gov Identifier: NCT01946204.

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.)