bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic mutations and homologous recombination deficiency (HRD) score in Japanese patients with metastatic hormone-sensitive prostate cancer (mHSPC): The impact of intraductal carcinoma of the prostate (IDC-P).
Authors: Kato Masashi , Yamamoto Akiyuki , Kawanishi Hideji , Naito Yushi , Akamatsu Shusuke , Tsuzuki Toyonori 
Published: January 2024

195 Background: Intraductal carcinoma of the prostate (IDC-P) is a significant prognostic factor associated with adverse clinical outcomes. A recent study has revealed significant associations between IDC-P and germline homologous recombination repair gene mutations (HRRm) and alterations in tumor suppressor genes. However, no study has investigated the association between IDC-P and gene mutations in a Japanese population. We evaluated the association between IDC-P in prostate core needle biopsies and gene mutations in metastatic hormone-sensitive prostate cancer (mHSPC) in a Japanese population. Methods: This study enrolled 102 mHSPC patients, classified as LATITUDE high-risk, diagnosed between 2018 and 2021 in Nagoya University and affiliated hospitals, all within three years of diagnosis, and with informed consent. Initial screening identified 106 patients with gene mutation data; four were excluded due to inadequate metastatic lesions or insufficient biopsy number. A single genitourinary pathologist assessed all biopsy slides according to 2019 ISUP grading system. Furthermore, the genetic analysis involved the examination of 108 genes using the Myriad myChoice HRD plus assay, alongside HRD (Homologous recombination deficiency) score analysis. Results: Our study achieved a 91% success rate in genomic testing. In total, 20 (19.6%) and 73 patients (71.6%) exhibited HRRm and molecular alterations in pathway other than HRR (MAOT-HRR), respectively. Notably, common HRRm included BRCA (n = 10; BRCA 1:2, BRCA 2:8) and CDK12 (n = 6) mutations, whereas common MAOT-HRR included FOXA1 (n = 30) and TP53 (n = 18) mutations. MAOT-HRR were more common in IDC-P positive patients (75.6% vs. 50%, p=0.06). PTEN and TP53 mutations were notably enriched in IDC-P positive patients (PTEN: 5.8% vs. 0%, TP53: 20.9% vs. 0%, p=0.06). Patients with IDC-P exhibited higher HRD scores (21.3 ± 8.8 vs. 16.6 ± 8.6, p = 0.06) compared to those without IDC-P, with CDK12 and BRCA mutations being more common in this group (CDK12: 7.0% vs 0%, BRCA: 10.5% vs 6.3%). In addition, the frequency of HRRm was slightly higher in patients with IDC-P compared to those without IDC-P (21% vs. 12.5%, p = 0.73). Finally, the frequency of genetic alterations (HRRm or MAOT-HRR) was significantly higher in patients with IDC-P positive patients (82.6% vs. 50%, p=0.0082). Conclusions: Among Japanese mHSPC patients, IDC-P demonstrates significant associations with an elevated incidence of genetic alterations and increased HRD score, emphasizing its potential clinical significance.
Genomic predictors of response and resistance to 177-Lu-PSMA-617 using circulating tumor DNA.
Authors: Muniz Miguel , Sartor A. Oliver , Bobek Olivia , Orme Jacob , Andrews Jack R. , Quevedo Fernando , Mahmoud Ahmed M. , Kase Adam McLain , Mosalem Osama M , Bryce Alan Haruo , Riaz Irbaz Bin , Thorpe Matthew , Burkett Brian J. , Kendi Ayse T. , Johnson Geoffrey , Ravi Praful , Kwon Eugene D. , Childs Daniel S 
Published: January 2024

220 Background: There is a critical need to identify biomarkers of response and resistance to 177Lu-PSMA-617. Post-hoc analyses of VISION have explored the prognostic and predictive value of select clinical parameters. However, we are still in the early stages of deciphering which molecular changes are associated with favorable or adverse treatment outcomes. Methods: We conducted a retrospective analysis of patients with metastatic castration-resistant prostate cancer (mCRPC), who received 177Lu-PSMA-617 at Mayo Clinic in Rochester, Minnesota, in the interval of March 2022 to March 2023. We included patients who provided research authorization, had a baseline PSA of at least 2 ng/mL, received at least 2 cycles of treatment, and had circulating tumor DNA (ctDNA) genomic profiling performed by Guardant (83 gene panel) within 60 days of treatment initiation. Clinical, laboratory, genomic, and radiomic parameters were abstracted by trained research personnel. Two independent analyses of “response” and “resistance” were performed. Response to treatment was defined as 50% or greater decrease in PSA from baseline (PSA50 response: dichotomized yes versus no), and resistance was defined as non-decreasing or rising PSA during treatment (PSA non-response: dichotomized yes versus no). Associations between gene alterations and response and resistance were evaluated via Fisher’s exact tests. Results: Between March 2022 and March 2023, 273 patients received cycle 1 of 177Lu-PSMA-617. A total of 108 patients met the inclusion criteria. The median number of cycles at data cutoff was 6 (IQR: 4,6) with 57 (53%) patients receiving all 6 planned cycles. The median PSA at baseline was 16.65 ng/ml (IQR: 5.20, 66.12). A total of 65 patients (60%) experienced a PSA50 response. No molecular alterations were associated with a higher rate of PSA50 response; however, alterations in ARID1A, AR, and CHEK2 were associated with lack of PSA50 response (Fisher’s exact p < 0.05). Of the 108 evaluable patients, 20 (19%) met criteria for PSA non-response. Alterations in AR, ARID1A, MYC, TP53, CHEK2, ATM, EGFR, and NOTCH1 were significantly associated with PSA non-response (Fisher’s exact p < 0.05); in each case, the presence of the alteration was positively associated with resistance (i.e., more instance of PSA non-response). No biomarkers were found to be inversely associated with PSA non-response. Conclusions: ctDNA assessed by commercially available, targeted sequencing panels prior to treatment may be useful in identifying the patients least likely to benefit from 177Lu-PSMA-617. Further work is ongoing to integrate ctDNA findings with clinical parameters in the hopes of understanding the factors mediating response and resistance to therapy.
Comparative effectiveness of ChatGPT 4.0 and medical oncologists in telemedicine-based management of metastatic prostate carcinoma (mPC).
Authors: Dal Emre , Srivastava Ayana , Chigarira Beverly , Hage Chehade Chadi , Narang Arshit , Gebrael Georges , Ji Richard , Agarwal Neeraj , Swami Umang , Li Haoran 
Published: January 2024

226 Background: The advent of telemedicine, accentuated during the COVID-19 pandemic, offers a prospective modality, especially when synergized with artificial intelligence (AI) tools such as ChatGPT 4.0. In this investigation, we sought to investigate the proficiency of ChatGPT vs. medical oncologists in the telemedicine-centric management of mPC. Methods: This IRB-approved retrospective study compared the competencies of ChatGPT and oncologists in conducting telemedicine consultations for patients with mPC. Out of 975 patients screened between April 1, 2022, and March 30, 2023, 102 met the inclusion criteria of having a diagnosis of mPC, attending at least one telemedicine consultation during the specified period, and having documentation available for two consecutive visits to enable the analysis of treatment decisions and outcomes. ChatGPT was asked to pre-chart and determine if a face-to-face consultation is needed. Its clinical competence was assessed using miniCEX, and medical decision-making (MDM). The Cohen's kappa test was used to measure the level of agreement between ChatGPT and oncologists in treatment decisions, and the Mann-Whitney U test was used to compare miniCEX and MDM. Results: The majority of patients were White (97.06%), with a median age of 75 years (range:53 to 99). Nearly all patients were diagnosed with adenocarcinoma (96.08%), with a median Gleason score of 7 (range: 6 to 10). The prevalent metastatic sites were bone (47.4%) and lymph nodes (44.16%). 26.88% had an ECOG score of 0, 54.84% had a score of 1, and 18.28% had a score greater than 1. Common coexisting conditions included diabetes mellitus (11.11%), hypertension (29.82%), hyperlipidemia (24.56%), and depression (7.6%). The primary outcome measured the concordance between ChatGPT and oncologists on whether to continue or cease the current treatment There was a statistical significance in sensitivity and specificity between clinicians and ChatGPT (Chi-squared=5.1, p=0.02). Cohen's Kappa showed a moderate concordance (Kappa = 0.43, p<0.001). There was no difference in the number of diagnoses made by the two parties (p=0.13 and 0.06, respectively). ChatGPT's median miniCEX score was 8 (SD=0.59), and its median MDM length was 41 words (SD=6.06). The average time saved by ChatGPT in pre-charting was 41 minutes (SD=6). Conclusions: ChatGPT showed moderate concordance with oncologists for the management of mPC in telemedicine. Subsequent investigations are needed to explore its potential in healthcare.
The 340B Drug Pricing Program and oral specialty drugs for advanced prostate cancer.
Authors: Faraj Kassem S , Kaufman Samuel , Herrel Lindsey A. , Oerline Mary , Caram Megan Veresh , Shahinian Vahakn B. , Hollenbeck Brent K. 
Published: January 2024

26 Background: Oral specialty drugs like abiraterone and enzalutamide are increasingly used in the management of men with advanced prostate cancer. However, the costs of these drugs can pose barriers to access and continued use, particularly in the socioeconomically disadvantaged population. The 340B program allows participating hospitals to purchase these medications at steep discounts, generating millions of dollars in savings per hospital. These savings afford them the opportunity to invest in programs (e.g., drug discounts) aimed at expanding their safety net. We assessed the effect of 340B participation on the care of men with advanced prostate cancer. Methods: A 20% sample of national Medicare claims data was used to perform a retrospective cohort study of men with advanced prostate cancer from 2012 through 2019 who received their care at a hospital. The primary outcome was the initial use of an oral specialty drug for prostate cancer and secondary outcomes included associated monthly out-of-pocket costs and adherence to treatment. To account for heterogeneity, we evaluated the effects of 1) hospital 340B participation, 2) socioeconomic status, using the social vulnerability index (SVI), and 3) the interaction between hospital 340B participation and SVI on each outcome. Results: Of the men with advanced prostate cancer, 2,237 (67%) and 1,100 (33%) received care at 340B participating and non-participating hospitals. There was no difference in the use of an oral specialty drug in men who received care at a hospital participating and not participating in the 340B program (22% vs 23% p=0.63). Conversely, when assessing variation across SVI, use of an oral specialty drug decreased with increased SVI (i.e., increased vulnerability; OR 0.95, p=0.038). However, the interaction between hospital 340B participation and SVI did not affect oral specialty drug use. Neither 340B participation, SVI, nor their interaction affected patient out-of-pocket costs. Additionally, although neither hospital 340B participation or SVI affected adherence to treatment, the interaction between 340B participation and SVI was significant (OR 1.2, p=0.040). This demonstrated that 340B was associated with better adherence to treatment among more socially vulnerable men. Conclusions: The 340B program did not affect the frequency of men with advanced prostate cancer who were started on an oral specialty drug. However, among those who were already started on therapy, 340B was associated with increased adherence to treatment in more socially vulnerable men. The underlying mechanism by which this occurred was unclear. In light of growing calls from policymakers to reform the 340B program, due to concerns regarding its effectiveness, policymakers could initially shift focus towards providing hospitals with guidance on how to effectively use savings to benefit those most in need.
The effect of dual eligibility on the quality of active surveillance in patients with newly diagnosed prostate cancer.
Authors: Faraj Kassem S , Dunn Rodney , Hollenbeck Brent K. , Shahinian Vahakn B. , Herrel Lindsey A. 
Published: January 2024

266 Background: Dual eligible beneficiaries are a particularly vulnerable group of patients who qualify for Medicare due to age and Medicaid due to low income. Fully dual eligible beneficiaries have access to additional support services that may facilitate coordination for their prostate cancer evaluation and treatment, while others (i.e., partial dual eligible beneficiaries) do not have access to these services. The extent to which these additional support services impact the quality of care in men on active surveillance for prostate cancer is unclear. Methods: We performed a cohort study of Medicare beneficiaries diagnosed with prostate cancer between 2015 and 2019. We identified men who were managed with active surveillance and evaluated the quality of care they received in the first year after diagnosis. Ideal surveillance was defined as having both 1-2 PSA tests and a confirmatory test (i.e., multiparametric MRI, genomics, or biopsy) at 1 year. Men who had testing below or above these thresholds were categorized as having “underuse” or “overuse” of active surveillance testing. Differences in active surveillance measures were compared between beneficiaries who were fully dual eligible, partially dual eligible, and those who were not dual eligible. Results: Of 138,785 men with newly diagnosed prostate cancer, 4,611 (3.3%) were fully dual eligible and 2,031 (1.5%) were partially dual eligible. In the year after diagnosis, 1488 (32%) fully dual eligible men, 638 (31%) partially dual eligible men, and 31,133 (31%) non-dual eligible men were managed with active surveillance. Of these men, the use of ideal surveillance was lower in dual eligible beneficiaries (full-11%, partial-9%, non-dual-15%, p<0.001). This corresponded to more underuse (full-70%, partial-74%, non-dual-63%) in dual eligible men and more overuse in non-dual eligible men (full-19%, partial-16%, non-dual-22%). The most common reasons for underuse were 1) both a lack of PSA and confirmatory testing in 26% of all men and 2) adequate PSA testing but no confirmatory test in 23% of all men. Conclusions: Our findings reveal that only a small minority of men with localized prostate cancer who are on active surveillance undergo ideal follow-up testing after diagnosis. Dual eligible men experienced less frequent ideal surveillance, potentially reflecting disparities in the quality of care for these vulnerable men. Partially dual eligible men had the worst rates of ideal surveillance and the highest rates of underuse, which may reflect the lack of support services that fully dual eligible men receive. Policymakers and healthcare providers aiming to improve the quality of active surveillance in the Medicare population should ensure that vulnerable groups have the resources needed to comply with the recommended testing.
Rural-urban disparities in prostate cancer survival: A population-based study.
Authors: Hu Siqi , Chang Chun-Pin , Dodson Mark W. , Deshmukh Vikrant , Newman Michael , Date Ankita , Sanchez Alejandro , Lloyd Shane , ONeil Brock , Hashibe Mia 
Published: January 2024

267 Background: Prostate cancer is the most prevalent malignancy among men in the United States. However, only a limited number of studies have explored the impact of rural-urban disparities in survival among prostate cancer patients with long-term follow-up. In order to investigate disparities in prostate cancer survival, we assess prostate cancer mortality and prognostic factors based on rural-urban residence. Methods: A cohort of 18,134 cancer patients with prostate adenocarcinomas diagnosed between 2004 and 2017 was identified. Residential location information at the time of cancer diagnosis was used to stratify on rural-urban residence. All-cause death and prostate cancer-cause death risks were estimated using Cox proportional hazard regression models. Results: Among prostate cancer patients, 15.1% resided in rural counties in Utah. Patients living in rural counties were different in demographic and clinical characteristics compared to their urban counterparts. An association was observed between rural residence and elevated risks of all-cause mortality (HR=1.19, 99%CI=1.10-1.29) and prostate cancer-specific mortality (HR=1.21, 99%CI=1.03-1.43). Elevated risks of both all-cause and prostate cancer-specific mortality were associated to factors such as unhealthy BMI, comorbidity index ≥1, family history of cancer or prostate cancer, single marital status, low income, low socioeconomic status, government insurance, earlier year of diagnosis, advanced prostate cancer stage, and extensive cancer treatment. Furthermore, the observed disparities in demographic and clinical profiles appeared to contribute to the disparities in all-cause and prostate cancer-specific mortality risks between rural and urban prostate cancer patients. Conclusions: Rural residence exhibited a significant association with the risk of prostate cancer-related and all-cause mortality. Patients residing in rural areas demonstrated distinct factors influencing mortality risks, encompassing both demographic and clinical aspects. These findings underscore the imperative for targeted interventions aimed at mitigating the rural-urban disparities in prostate cancer outcomes.
Identifying racial disparities in adverse dispositions following major surgery for prostate cancer using machine learning.
Authors: Khosla Atulya Aman , Batra Nitya , Ganiyani Mohammad Arfat , Jatwani Karan , Singh Rohit , Chedella Venkata Lakshmi Prajwala , Roy Mukesh , Ramamoorthy Venkataraghavan , Rubens Muni B. , Saxena Anshul , Garje Rohan , Jaiyesimi Ishmael A. 
Published: January 2024

269 Background: Machine learning has shown potential in accurately predicting outcomes after urologic surgery, allowing for improved patient selection, risk stratification, and predicting discharge dispositions. Healthcare disparities pose a major public health challenge, leading to unequal health outcomes for different patient groups. Successful measures to mitigate these disparities rely on precise recognition of the demographic groups impacted. In this study, we utilized AI and ML models to predict such adverse outcomes so that early intervention may lead to timely and optimal prostate cancer care. Methods: Using the 2016–2021 ACS National Surgical Quality Improvement Program (NSQIP) data, we identified 84,064 patients who underwent prostatectomy or surgeries related to excision of the prostate. We used Gradient Boosted Trees, Random Forests, and Deep Learning to examine the association between various variables from demographic, clinical, preoperative labs, past medical history domains, and non-home discharge disposition after cancer surgery. Accuracy rates were utilized to compare various models. Results: The median [Q1, Q3] age of the sample was 65.0 [59.0, 69.0] years. The total median [Q1, Q3] hospital length of stay and operation time of the sample was 1.0 [1.0, 2.0] days and 200.0 [153.0, 257.0] minutes, respectively. White non-Hispanic (WNH) patients constituted 62% (n = 52,444) of the sample, and Black non-Hispanic (BNH) were 11% (n = 9547). Smoking prevalence was higher among BNH cases (18.6%) as compared to WNH cases (10.9%). The proportion of cases requiring hypertension medication was 66.6% among BNH compared to 52.6% among WNH. The 30-day readmission rates for WNH, BNH, and White Hispanic (WH) cases were 6.4%, 6%, and 5.6%, respectively. The mortality rates for WNH, BNH, and WH cases were 0.3%, 0.3%, and 0.2%, respectively. The non-home discharge rates for WNH, BNH, and WH cases were 19.8%, 20.6%, and 22.4%, respectively. The machine learning model results showed that the Deep Learning model performed best in predicting discharge disposition after prostatectomy for prostate cancer, with an accuracy of 80.48%. Race was present in the list of important factors, indicating that race had a significant association with the outcome. Conclusions: Our study demonstrated that using a national registry, ML models can accurately identify patient populations affected by healthcare disparities. We found that racial disparities in adverse dispositions persisted after adjusting for covariates. Interventions aimed at reducing these disparities are warranted to improve the quality of life of this subgroup of patients. [Table: see text]
i-Biomarker CaDx: A circulating miRNA-based multi-cancer detection tool with explainable AI for prostate cancer.
Authors: Floares Alexandru George , Zety Adrian Vasile , Floares Carmen , Calin George , Kreutz Carvalho Eduardo , Manolache Florin 
Published: January 2024

272 Background: Prostate cancer is a pressing concern, demanding early and accurate detection for effective intervention. Conventional methods, like digital rectal exams and prostate-specific antigen (PSA) tests, often lack the required specificity. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers for various cancers, including prostate cancer. The i-Biomarker CaDx is a cutting-edge, technology-neutral platform designed for multi-cancer early detection, boasting an impressive accuracy rate of 99-100%. This study aims to assess the effectiveness of i-Biomarker CaDx specifically for prostate cancer using publicly endorsed datasets while leveraging explainable artificial intelligence (XAI) to gain deeper insights. Methods: The utilized dataset (GSE112264) contains 809 prostate cancer patients matched with an equal number of age-matched healthy controls from multiple datasets. Microarray technology was employed to profile circulating miRNAs. A diverse range of classification paradigms, including decision trees, neural networks, and support vector machines, were utilized for attribute identification, classification, and seamless integration of XAI. Rigorous hyperparameter optimization was conducted, and the best-performing classifiers were amalgamated into the final model, weighted by their respective efficacies. We assessed i-Biomarker CaDx's performance through rigorous cross-validation and independent test datasets. The XAI component provided detailed insights into miRNA variations associated with diagnostic outcomes. Results: Our findings reveal that i-Biomarker CaDx exhibits exceptional diagnostic accuracy, achieving a remarkable 100% accuracy rate when evaluated on the designated dataset. Diagnostic metrics, including sensitivity, specificity, and predictive values, surpass conventional prostate cancer diagnostic methods like digital rectal exams and PSA tests. The designed models, incorporating decision trees, neural networks, and support vector machines, effectively decipher intricate miRNA relationships relevant to prostate cancer using XAI. Thus, our analyses shed light on miRNA patterns and their associations with prostate cancer, enhancing the understanding of the underlying molecular complexities of the disease. Conclusions: i-Biomarker CaDx, a pioneering technology-agnostic multi-cancer early diagnostic platform, demonstrates outstanding performance in detecting prostate cancer, surpassing traditional diagnostic methods. The integration of XAI allows for in-depth exploration of miRNA alterations and their impact on prostate cancer, enriching our interpretations at both the population and individual levels. These findings underscore the substantial potential of i-Biomarker CaDx as a transformative, non-invasive diagnostic tool for prostate cancer.