bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning models for reinjury risk prediction using cardiopulmonary exercise testing (CPET) data: optimizing athlete recovery
Authors: Abasi Arezoo , Nazari Ahmad , Moezy Azar , Fatemi Aghda Seyed Ali
Published: February 2025

Background

Cardiopulmonary Exercise Testing (CPET) provides detailed insights into athletes’ cardiovascular and pulmonary function, making it a valuable tool in assessing recovery and injury risks. However, traditional statistical models often fail to leverage the full potential of CPET data in predicting reinjury. Machine learning (ML) algorithms offer promising capabilities in uncovering complex patterns within this data, allowing for more accurate injury risk assessment.

Objective

This study aimed to develop machine learning models to predict reinjury risk among elite soccer players using CPET data. Specifically, we sought to identify key physiological and performance variables that correlate with reinjury and to evaluate the performance of various ML algorithms in generating accurate predictions.

Methods

A dataset of 256 elite soccer players from 16 national and top-tier teams in Iran was analyzed, incorporating physiological variables and categorical data. Several machine learning models, including CatBoost, SVM, Random Forest, and XGBoost, were employed to predict reinjury risk. Model performance was assessed using metrics such as accuracy, precision, recall, F1-score, AUC, and SHAP values to ensure robust evaluation and interpretability.

Results

CatBoost and SVM exhibited the best performance, with CatBoost achieving the highest accuracy (0.9138) and F1-score (0.9148), and SVM achieving the highest AUC (0.9725). A significant association was found between a history of concussion and reinjury risk (χ² = 13.0360, p = 0.0015), highlighting the importance of neurological recovery in preventing future injuries. Heart rate metrics, particularly HRmax and HR2, were also significantly lower in players who experienced reinjury, indicating reduced cardiovascular capacity in this group.

Conclusion

Machine learning models, particularly CatBoost and SVM, provide promising tools for predicting reinjury risk using CPET data. These models offer clinicians more precise, data-driven insights into athlete recovery and risk management. Future research should explore the integration of external factors such as training load and psychological readiness to further refine these predictions and enhance injury prevention protocols.
Sodium butyrate attenuates microglia-mediated neuroinflammation by modulating the TLR4/MyD88/NF-κB pathway and microbiome-gut-brain axis in cardiac arrest mice
Authors: Sun Jianfei , Lu Liping , Lian Yingtao , Xu Song , Zhu Ying , Wu Yanping , Lin Qianhui , Hou Jing , Li Yinping , Yu Zhui
Published: February 2025

Cardiac arrest (CA) is one of the most common illnesses worldwide. Post-CA brain injury (PCABI) is a major cause of death and poor recovery in CA patients and the current CA treatments are not very effective. The microbiome-gut-brain axis has been found to significantly affect brain ischemia injury. Furthermore, in ischemic stroke patients, short-chain fatty acids (SCFA), especially sodium butyrate (SB), have been observed to promote neuroprotective effects by modulating inflammatory response and microglial polarization in the cortex. However, the precise mechanism of SB on CA-induced injury remains elusive. Therefore, this research study established an oxygen–glucose deprivation and reoxygenation (OGD/R) model using BV-2 microglial and HT22 cells to simulate cerebral ischemia/reperfusion injury in vitro and a potassium chloride-induced CA mouse model to mimic CA in vivo. The data revealed that SB markedly improved neurological scores and reduced neuronal death and apoptosis. Moreover, it reduced M1 microglia and neuroinflammation in CA mice. In addition, SB increased intestinal integrity and alleviated systemic inflammation. The 16S rDNA sequencing analysis indicated that SB intervention mitigated CA-induced gut microbiota dysbiosis and SCFA depletion. It was also observed that CA mice’s brain and OGD/R-exposed BV2 cells had substantially increased levels of MyD88, phosphorylated NF-κB p65, and TLR4 proteins, which were reduced after SB treatment. In summary, this study revealed that SB can protect against cerebral ischemia–reperfusion injury by controlling microglia polarization and microbiome-gut-brain axis to inhibit brain inflammation via the TLR4/MyD88/NF-κB pathway.
Occipital artery–posterior inferior cerebellar artery bypass for anterior inferior cerebellar artery stenosis with repeated cerebellar ischemic stroke: a case report
Authors: Eguchi Hiroki , Arai Takashi , Kawamata Takakazu
Published: February 2025

Background

Vertebrobasilar insufficiency revascularization has long been a preventive treatment for cerebral infarction. However, no studies have demonstrated the efficacy of revascularization in patients with cerebellar ischemia.

Case presentation

We present the case of a 77-year-old Japanese man who experienced seven recurrent cerebellar infarctions over 2 years. Severe stenosis was noted at the origin of the common trunk of the posterior inferior cerebellar artery and anterior inferior cerebellar artery. Patients with cerebral infarctions are resistant to medical treatment. Blood flow evaluation showed that the area of reduced cerebrovascular reactivity corresponded to the area where repeated small infarctions occurred. An occipital artery–posterior inferior cerebellar artery bypass was performed to prevent another infarction. Postoperative single-photon emission computed tomography showed an improved cerebrovascular reactivity. No ischemic events occurred during 2 years of a postoperative follow-up period.

Conclusion

Occipital artery–posterior inferior cerebellar artery bypass is an effective treatment method for vascular stenosis and decreased blood circulation due to posterior circulation ischemia.
Evaluating biparametric MRI for diagnosing muscle-invasive bladder cancer with variant urothelial histology: a multicenter study
Authors: Liu Peikun , Cai Lingkai , Que Hongliang , Jiang Meihua , Jiang Xuping , Liang Bo , Wang Gongcheng , Jiang Linjing , Yang Xiao , Lu Qiang
Published: February 2025

Background

Vesical Imaging-Reporting and Data System (VI-RADS) based on multiparametric MRI (mp-MRI) demonstrated excellent performance in diagnosing muscle-invasive bladder cancer (MIBC) in cases of pure urothelial carcinoma. However, the performance of VI-RADS based on mp-MRI and biparametric MRI (bp-MRI) in diagnosing urothelial carcinoma with variant histology (VUC) remains unknown.

Purpose

To evaluate the applicability of VI-RADS using mp-MRI and bp-MRI in diagnosing MIBC in patients with VUC.

Methods

A retrospective analysis was conducted on 86 patients with VUC from different medical centers. Each patient underwent mp-MRI, with images evaluated using VI-RADS scores. The acquired images were divided into two groups: the mp-MRI group and the bp-MRI group. The mp-MRI group was evaluated according to the VI-RADS protocol. For the bp-MRI group, two VI-RADS scoring criteria were established: bp-DWI, primarily driven by DWI, and bp-T2WI, primarily driven by T2WI. The bp-MRI group was evaluated based on these two criteria. Inter-reader agreement performance was evaluated using Kappa analysis. The evaluation methods were evaluated by receiver operating characteristic curve. Comparison of the area under the curve (AUC) was performed used DeLong’s test. A p-value < 0.05 was considered significant.

Results

Inter-reader agreement was high across all evaluation methods, with Kappa values exceeding 0.80. The AUCs for mp-MRI, bp-DWI, and bp-T2WI were 0.934, 0.885, and 0.932, respectively. The diagnostic performance of bp-T2WI was comparable with that of mp-MRI (p = 0.682) and significantly higher than bp-DWI (p = 0.007). Both mp-MRI and bp-T2WI demonstrated high sensitivity and specificity.

Conclusion

VI-RADS based on mp-MRI demonstrates good diagnostic performance for MIBC in VUC patients. bp-T2WI may provide comparable diagnostic performance to mp-MRI.
Identification of biomarkers and mechanism exploration of ferroptosis related genes regulated by m6A in type 2 diabetes mellitus
Authors: Wang Jing , Li Xuying , Geng Juan , Wang Ruiduo , Ma Gang , Liu Pan
Published: February 2025

Purpose

This study is aims to explore the role of ferroptosis genes regulated by N6-methyladenosine (m6A) in Type 2 diabetes mellitus (T2DM).

Material and methods

Firstly, differentially expressed m6A-FRGs (DEm6A-FRGs) were obtained by intersecting the differentially expressed genes (DEGs) and the m6A-related ferroptosis genes (m6A-FRGs). After enrichment analysis of DEm6A-FRGs, artificial neural network (ANN) and nomogram models were constructed using 4 biomarkers. Moreover, the gene set enrichment analysis of biomarkers was performed. Furthermore, the transcription factors (TF)-mRNA and competing endogenous RNAs (ceRNA) regulatory networks were constructed to reveal the potential regulation of biomarkers at molecular level. In addition, the targeted drugs of biomarkers were predicted, and the molecular docking was used to study the inter-molecular interactions between biomarkers and targeted drugs by “AutoDockvina”.

Results

Totals of 10 DEm6A-FRGs were obtained by intersecting the 402 DEGs and 299 m6A-FRGs. Moreover, the ANN model and nomogram model were constructed with 4 biomarkers including CDKN1A, MIOX, MYCN and CD82, among them, CDKN1A was the most important biomarker for forecasting T2DM. Notably, the function of extracellular matrix structural constituent was low expression in CD82 and MIOX, the function of mitochondrial protein-containing complex was high expression in CD82 and CDKN1A. Furthermore, TP63 could regulate CD82, CDKN1A and MIOX, GATA3 could regulate CD82, CDKN1A and MYCN at the same time. The ceRNA network was constructed with 4 mRNAs, 51 miRNAs and 37 lncRNAs, among them, XIST was a key lncRNA that associated with 12 miRNAs, which could influence CDKN1A. In addition, bisphenol A was associated with CD82 and MYCN, CGP 25608 was associated with CDKN1A and MIOX.

Conclusion

This study revealed the potential molecular mechanisms of m6A-related ferroptosis genes in T2DM, which could provide novel insights for the clinical diagnosis and treatment of T2DM.
Intracranial pressure estimated non-invasively and postoperative outcomes in surgery in the Trendelenburg position with pneumoperitoneum
Authors: von Knorring Christina , Gjordeni Megan , Thomsson Tina , Lindström Ann-Charlotte , Pansell Jakob
Published: February 2025

Background

Surgery in the Trendelenburg position (TP) with pneumoperitoneum (PP) is beneficial in several aspects but is associated with postoperative complications, such as postoperative nausea and vomiting (PONV). The mechanism behind this is unknown, but an increase in intracranial pressure (ICP) has been suggested. There are several studies of non-invasively estimated ICP during surgery in TP with PP. The association between perioperative estimated ICP and postoperative complications has not yet been reviewed.

Methods

We performed a scoping review of peer-reviewed clinical studies reporting on both perioperative estimation of ICP and postoperative complications in patients undergoing surgery in TP with PP. The literature search was performed in February 2025 on PubMed, CINAHL, and Web of Science.

Results and conclusions

Ten of 12 included studies suggested associations between perioperative elevation of estimated ICP and postoperative complications, most notably PONV. This may have clinical implications since elevated ICP can be treated. Future research should focus on the association between perioperative ICP estimation and postoperative complications and the effects of ICP-lowering strategies on postoperative outcomes.
Efficient strategies and troubleshooting for single particle cryoEM data collection using EPU
Authors: Bhandari Janarjan , Kompaniiets Dmytro , Singh Ajit Kumar , Bator Carol , Porta Jason , Liu Bin
Published: February 2025

Background

CryoEM has gained popularity due to advancements in both hardware and software, making it possible to visualize biological molecular structures in detail. However, despite its growing use, cryoEM remains a costly technique, and limited access to cryo-capable TEMs is slowing research efforts. By refining experimental design and streamlining data collection approaches, researchers can significantly boost efficiency and reduce costs, making this technique more accessible and impactful.

Method

This work presents a guide to some of the session setup parameters for automated cryoEM data collection using Thermo Fisher’s EPU software.

Results

The TIFF and MRC formats were compared, and the Faster acquisition mode was evaluated against the Accurate acquisition mode. Acquired TIFF files were significantly smaller than MRC files without any notable loss of resolution in the data. By minimizing stage movements, the Faster acquisition mode increases data collection speed, while Accurate acquisition provides precise centering on the optical axis. The models generated from all experiments exhibit similar resolutions, approximately 2.12 Å. These findings suggest that the Faster mode, coupled with recent advancements in hardware and software, can increase data collection speed by nearly 5 times.

Discussion

This guide offers practical insights into optimizing data collection strategies based on the study's target and sample nature. Such optimization ensures the efficient use of resources, leading to reduced costs and time during both data collection and processing. Based on our findings, we recommend using the Faster mode with counted super-resolution, binning 2, and non-gain normalized TIFF output file format for all strategies outlined below.
Co-Occurrence of Cytogenetic Abnormalities and High-Risk Disease in Newly Diagnosed and Relapsed/Refractory Multiple Myeloma
Authors: Kaiser Martin F. , Sonneveld Pieter , Cairns David A. , Raab Marc S. , San-Miguel Izquierdo Jesús , Zhang Rick , Acosta Jorge , Larocca Alessandra , Popat Rakesh , Li Cong , Baertsch Marc-A. , Brown Sarah R. , Lahuerta Palacios JuanJose , Gandhi Anita K. , Macé Sandrine , Musto Pellegrino , Yong Kwee , Mai Elias K. , Dubin Franck , Blade Joan , Capra Andrea , Cook Gordon , Bertsch Uta , Mateos María-Victoria , Boccadoro Mario , Jackson Graham H. , Gutiérrez Norma C. , Gay Francesca , Weinhold Niels
Published: February 2025

PURPOSE

Survival for patients with multiple myeloma (MM) has improved but outcomes remain heterogeneous. Consistent diagnostic identification of high-risk disease is desirable to address unmet patient need. The aim was to investigate the consistency of association of co-occurrence of high-risk cytogenetic abnormalities (HRCAs) with prognosis in patients with newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM), and across a range of treatment modalities.

METHODS

A systematic review of randomized controlled trials of MM that reported testing for HRCA between January 1, 2000, and December 9, 2021, was performed. Groups were contacted and asked to locally perform a novel, federated analysis of their data for single hit (one HRCA) and double hit (≥two HRCAs), using a centrally provided algorithm. Analysis results were centrally collated and meta-analyzed to assess the hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) for one/≥two HRCAs across patient subgroups using random-effects models.

RESULTS

Twenty-four trials including 13,926 patients were included. The median age of participants was 66.5 years (IQR, 59-72) and 56.5% were male (IQR, 52-60). The HR for PFS was 2.28 (95% CI, 2.05 to 2.54) for patients with ≥two HRCAs and 1.51 (95% CI, 1.38 to 1.65) for patients with one HRCA. The HR for OS was 2.94 (95% CI, 2.49 to 3.47) and 1.69 (95% CI, 1.52 to 1.88) for the two subgroups, respectively. In studies initiated since 2015, the effect abides (≥two HRCA PFS, HR, 2.39 [95% CI, 1.96 to 2.91]; OS, 3.10 [95% CI, 2.10 to 4.60]) both for NDMM and RRMM. Heterogeneity related to transplant eligibility and relapsed/refractory status was as expected.

CONCLUSION

The association of ≥two HRCAs with the poorest outcome in NDMM and RRMM, and across treatment modalities, as demonstrated here for the first time to our knowledge, allows for more focused development of novel approaches to these patients with high unmet need.
Evaluation of time to metastasis (TTM) from prostatectomy and survival in patients (pts) with metachronous metastatic hormone-sensitive prostate cancer (mHSPC) receiving androgen deprivation therapy (ADT) intensification: A real-world study.
Authors: Sayegh Nicolas , Jo Yeonjung , Ozay Zeynep Irem , Hage Chehade Chadi , Gebrael Georges , Ostrowski Micah , Campbell Patrick , HU Siqi , Tripathi Nishita , Nordblad Blake , Chigarira Beverly , Ji Richard , Galarza Fortuna Gliceida M , Mathew Thomas Vinay , Maughan Benjamin L. , Swami Umang , Agarwal Neeraj
Published: February 2025

100

Background:
Metachronous mHSPC is associated with improved outcomes compared to synchronous (de novo) mHSPC. However, there are limited data on the effect of TTM after radical prostatectomy in patients with metachronous mHSPC treated with systemic therapies. Our objective was to explore the association of TTM after prostatectomy with survival outcomes in a real-world population.
Methods:
In this IRB-approved retrospective study, eligibility criteria were: pts with metachronous mHSPC who underwent radical prostatectomy and were treated with ADT plus androgen receptor pathway inhibitor (ARPI). Metachronous disease was defined as the absence of metastatic disease within 90 days of initial prostate cancer diagnosis. TTM was defined from the time of prostatectomy to the time of initial metastatic diagnosis and was analyzed as a continuous variable, then categorized. Progression-free survival (PFS) was defined from the start of therapy for mHSPC to disease progression or death from any cause. Overall survival (OS) was defined from treatment initiation for mHSPC to death from any reason or censored at the last follow-up. Multivariable analyses for PFS and OS were performed using a Cox proportional hazards model, adjusting for disease volume (per CHAARTED criteria), Gleason score, log-transformed PSA, and age.
Results:
Overall, 186 pts with metachronous mHSPC who previously underwent prostatectomy were eligible and included. Pts with a Gleason score of ≥ 8 comprised 44% of the cohort and those with age ≥ 65 comprised 68% of the cohort. A high volume of disease was present in 34% of the pts. Overall, median TTM was 46 months. On univariate analysis, a longer TTM was not associated with improved PFS (HR 1.0, 95% CI 1.0-1.1, P=0.3) or OS (HR 1.0, 95% CI 1.0-1.1, P=0.8), and results were consistent on multivariate analysis. No PFS or OS benefit was observed in pts achieving a TTM ≥1, 2, 3, and 4 years respectively, versus those who do not (Table).
Conclusions:
A prolonged TTM is not associated with survival outcomes after onset of metachronous mHSPC in pts treated with ADT + ARPI. OS and PFS in the mHSPC setting appear to be independent of timing of metastatic disease post prostatectomy in this pt population.

Univariate
Multivariate

HR (P-value)

PFS

OS

PFS

OS

TTM Continuous
1.0 (0.3)
1.0 (0.8)
1.0 (0.5)
1.0 (0.4)

TTM <1 vs ≥1
0.9 (0.7)
0.8 (0.6)
0.7 (0.5)
0.7(0.5)

TTM <2 vs ≥2
0.9 (0.8)
0.9(0.7)
0.6 (0.3)
0.6 (0.3)

TTM <3 vs ≥3
0.9 (0.5)
0.8 (0.6)
0.6 (0.2)
0.6 (0.2)

TTM <4 vs ≥4
0.9 (0.7)
1.1 (0.7)
0.9 (0.7)
0.9 (0.7)
Clinical features and prognostic value of CDK12 mutation in prostate cancer patients.
Authors: Tao Hanyang , Dong Baijun
Published: February 2025

103

Background:
Studies have reported that biallelic loss of CDK12 in prostate cancer patients leads to genomic instability and an increase in tandem duplications. However, the prognostic relevance of CDK12 mutations has not been fully validated. Therefore, we assessed the clinical characteristics and outcomes of prostate cancer patients with CDK12 mutations, comparing this genomic subtype with prostate cancer lacking any genetic alterations.
Methods:
A total of 141 prostate cancer patients diagnosed between November 2010 and March 2024 were included. Genomic characteristics of biopsy tissues or plasma ctDNA were analyzed using next-generation sequencing to identify patients with CDK12 mutations and those without any genetic mutations. Due to the low incidence of biallelic CDK12 loss in this patient cohort, we integrated data from metastatic tumor biopsies and liquid biopsies. Notably, cfDNA and prostate cancer tumor biopsies from the same individuals have shown strong concordance in identifying somatic alterations.
Results:
We evaluated the clinical characteristics of the two groups of prostate cancer patients, and patients with CDK12 mutations were more aggressive and had a higher proportion of initial metastasis [77.05% (47/61) vs. 56.67% (51/80), P=0.013]. The median PSA at diagnosis was higher (60.63ng/ml vs. 38.02ng/ml), and the proportion of pathological Gleason score ≥8 was higher (85.25% (52/61) vs. 60.00% (48/80), P < 0.01). Patients with localized CDK12 mutations had shorter time to metastasis (median 34.10 months vs. 56.22 months, p < 0.001) and shorter survival than those without deleterious genetic alterations. Patients with CDK12 mutations had shorter median progression-free survival with conventional androgen-deprivation therapy, abiraterone, and docetaxel than those without deleterious mutations. However, the use of novel anti-male therapy, PARPi, immunotherapy or focal ablation can still prolong the survival of patients.
Conclusions:
CDK12 mutations are associated with metastasis and higher pathological malignancy, and they also serve as a predictive factor for poor clinical outcomes in patients receiving standard androgen deprivation therapy, abiraterone, or docetaxel treatment. Therefore, prostate cancer patients with CDK12 mutations may need to consider novel anti-androgen therapies, or combined interventions such as PARP inhibitors, immunotherapy, or focal treatments. This study underscores the importance of molecular diagnostics and the necessity of employing appropriate therapeutic strategies for CDK12-mutated prostate cancer. Overall, given the significant heterogeneity in clinical behavior, our research highlights the importance of this molecular subtype in prostate cancer and serves as a foundation for future prospective studies to further characterize the CDK12 subtype in prostate cancer.
Progressive T cell exhaustion and predominance of aging tissue associated macrophages with advancing disease stage in penile squamous cell carcinoma.
Authors: Miyagi Hiroko , Yu Xiaoqing , Peak Taylor , Dhillon Jasreman , Le Casey , Wang Xuefeng , Yoder Sean J. , Marchion Douglas C. , Lu Xin , Pettaway Curtis Alvin , Segura Carlos Moran , Roman Souza Gabriel , Yu Alice , Zhang Chaomei , Zemp Logan , Spiess Philippe E. , Chahoud Jad
Published: February 2025

11

Background:
Penile squamous cell carcinoma (PSCC) is a rare malignancy with limited understanding of the tumor immune microenvironment (TIME). The interplay between PSCC and the immune system across disease progression and HPV infection status remains poorly characterized. This study aims to assess the TIME changes from localized to advanced disease and between HPV-positive versus negative tumors, we hope to identify potential immune evasion mechanisms for advanced PSCC.
Methods:
scRNA-seq was performed on ten PSCC tissue samples from penile, lymph node and distant metastatic sites with four matched penile and lymph node samples to understand the cellular heterogeneity within PSCC tumors. Analysis of immune cell populations and transcriptional hallmarks were performed stratified by localized (pT1-3, N0) versus advanced (N1-3, M0 or any N, M1) disease states and HPV infection status.
Results:
Patients with advanced stage disease were found to have a TIME enriched with terminally exhausted C8+ T cells. The myeloid compartment showed an increase in aging and immunosuppressive M2-like macrophages. Additionally, hypoxia-induced response patterns were more pronounced in advanced stages. HPV-negative tumors exhibited a quiescent TIME characterized by low immune cell infiltration.
Conclusions:
We observed significant differences in immune cell infiltration between localized and advanced PSCC disease states. Advanced disease states demonstrated an exhausted immune phenotype, characterized by terminally exhausted CD8
+
T cells, M2-like macrophages and hypoxic signature. HPV-negative tumors displayed low immune cell infiltration. These findings offer valuable insights into the evolving PSCC immune landscape, paving the way for the development of potential novel macrophage directed therapies for PSCC.
Evaluating clinical tools to monitor cardiovascular (CV) risk in men with localized high-risk or locally advanced prostate cancer (LHRPC) treated with hormone therapy (HT).
Authors: Venkatesh Neha , Chauhan Pankaj Kumar , Grewal Kabir , Aparicio Ana , Pilié Patrick Glen , Subudhi Sumit Kumar , Corn Paul Gettys , Siddiqui Bilal Ahmed , Zurita Amado J. , Frigo Daniel , Logothetis Christopher , Msaouel Pavlos , Koutroumpakis Efstratios , Hahn Andrew Warren
Published: February 2025

116

Background:
Androgen deprivation therapy (ADT) and androgen receptor signaling inhibitors (ARSIs) indirectly increase CV risk. There are no risk estimation tools specific to men with prostate cancer undergoing HT. Current practice utilizes tools designed for the general population, such as the AHA/ACC ASCVD risk score. Herein, we investigate the applicability of such general population risk tools in men receiving pre-operative HT for LHRPC.
Methods:
We conducted a retrospective analysis of men with LHRPCa who received 6 months of pre-operative ADT + apalutamide +/- abiraterone on NCT. Cardiometabolic factors of interest were extracted from the electronic medical record, and ASCVD risk scores were calculated alongside metabolic syndrome (MetS) Z scores (calculated using ASCVD calculator
https://tools.acc.org/ldl/ascvd_risk_estimator/#!/calulate/estimator/
and metabolic syndrome severity calculator

https://metscalc.org/metscalc/
).
Results:
Sixty-four patients had data available to calculate baseline and end-of-treatment (EOT) ASCVD risk and MetS Z scores. Prior to initiation of HT, 46.8% of patients were on antihypertensive treatment, 11.3% had diabetes mellitus, and 45.2% were on lipid-lowering therapy. After 6 months of ADT + ARSI, the median change in ASCVD risk score was 0.95, and 21% of patients exhibited a clinically significant increase in ASCVD risk score of ≥ 2.5%. The median change in the metabolic syndrome Z score was -0.36, indicating a decrease in metabolic syndrome risk. 28% of all patients demonstrated an increase in metabolic syndrome risk after 6 months of HT.
Conclusions:
Despite the known association between HT and increased CV risk, most patients in this study did not experience a clinically meaningful increase in either ASCVD risk or MetS Z score. These findings suggest that general population risk estimation tools may not reflect temporal evolution of CV risk in patients undergoing HT. This study also highlights an unmet need for novel risk assessment tools specifically tailored to identify at-risk men among those treated with HT.
Impact of pre-existing diabetes mellitus on acute care use in older patients with metastatic prostate cancer on androgen receptor signaling inhibitors.
Authors: Liu Michael A. , Raghunathan Rohit R. , Runcie Karie , Wang Shikun , Wright Jason Dennis , Wei Alexander Z , Stein Mark N. , Hershman Dawn L.
Published: February 2025

119

Background:
Androgen receptor signaling inhibitors (ARSIs) are mainstay treatments for metastatic prostate cancer. Hyperglycemia is a common side effect but limited data exists on outcomes such as hospitalizations in patients with diabetes mellitus (DM) starting on ARSIs.
Methods:
We used the SEER-Medicare linked data for patients aged 66 and older with de novo metastatic prostate cancer who were prescribed abiraterone, enzalutamide, or apalutamide per part D files from 2011 to 2019. Eligible patients had continuous Medicare Part A/ B coverage before and after drug initiation, and Part D coverage before initiation. Patients were excluded if they died within 6 months of diagnosis or received chemotherapy prior to ARSI (<1%). Univariate associations between covariates and DM were assessed using chi-square tests or t-tests. Negative binomial regression was used to calculate incidence rate ratios of acute care use (total number of hospital or emergency admissions divided by total time at risk) for each model covariate among DM and non-DM patients after initiation of ARSI.
Results:
2697 patients met eligibility criteria, of which 17.4% (469) had DM. The average age of the cohort was 75.0 years ±7.0 SD. 85.3% (2300) of patients received androgen deprivation therapy (ADT) prior to ARSI, and 0.9% (24) received ADT afterwards. 28.3% (773) of patients received abiraterone only, 23.8% (641) received only enzalutamide or apalutamide, and 47.6% (1283) received both treatments. Patients with DM (vs without) differed significantly with regards to lower high school education, higher NCI comorbidity score (excluding DM), and less receipt of abiraterone, but not in age, race, marital status, prior ADT treatment, or receipt of enzalutamide or apalutamide. 29.5% (797) of patients had acute care use within 6 months, with 39.9% (187) in the DM group and 27.4% (610) in the non-DM group (
p
<.0001), Adjusted for covariates, patients with DM had a 41% increased rate of acute care use (
p
=0.0016) compared to those without DM. Additionally, compared to those prescribed only enzalutamide or apalutamide, patients prescribed abiraterone had a 47% increased rate of acute care use (
p
=0.0026); this was independent of having DM (interaction
p
=0.77).
Conclusions:
Patients with pre-existing DM on ARSIs experienced higher rates of acute care use compared to those without DM, regardless of ARSI type. Future studies should assess potential interventions in older patients with diabetes on ARSIs, such as close monitoring of glycemic status or adherence to risk reduction medications.
Baseline fracture risk for prostate cancer patients initiating long-term androgen deprivation therapy.
Authors: Trinh Jonathan , Frimpong Sandra , Zhan Yue , Samson Kaeli , Graeff-Armas Laura A. , Teply Benjamin A.
Published: February 2025

122

Background:
Androgen deprivation therapy (ADT) is essential for management of advanced prostate cancer, yet it carries risks including osteoporosis and fragility fractures. Antiresorptive therapy is recommended to reduce fractures for patients at high risk. However, precisely which patients should undergo formal screening with dual-energy X-ray absorptiometry (DEXA) at baseline has been relatively unexplored. This study aims to describe these baseline fracture risks, the utility of DEXA screening based upon Fracture Risk Assessment Tool (FRAX) scores, and the impact of specific risk factors in this population.
Methods:
We performed a retrospective cross-sectional study of patients at our institution with prostate cancer treated with ≥1 year of ADT between 2011 and 2024. Patients were excluded if their FRAX scores were incalculable or if they received antiresorptive therapy prior to starting ADT. Ten-year hip and combined major osteoporotic fracture risks were calculated using FRAX without femoral neck T-scores for all patients and with femoral neck T-scores for patients who received DEXA scans. A high fracture risk was defined as a 10-year hip fracture ≥3% or a combined major osteoporotic fracture risk ≥20%. Differences between dichotomous groups were assessed using independent samples t-tests, Chi-square tests, or Fisher’s exact tests.
Results:
We identified 515 patients with an average age of 70.1 years and average BMI of 29.5 kg/m
2
. Four hundred and forty-eight (87%) patients received leuprolide as ADT, 70 (13.6%) patients were on a prednisone-containing regimen, and 66 (12.8%) patients were active smokers. Based upon clinical data at ADT initiation (without including T-scores from DEXA), 201 (39.0%) patients had a high 10-year risk of hip or combined major osteoporotic fracture by FRAX. Among the 183 patients who did have DEXA scans, 85 (46.4%) met criteria for osteopenia while 14 (7.7%) had osteoporosis by T-score. Additionally, 48 (26.2%) patients had high 10-year fracture risks by FRAX and met criteria for initiation of antiresorptive therapy. The patients meeting criteria for antiresorptive therapy, in general, were older (73.3 years vs. 67.9 years) and weighed less (87.8 kilograms vs. 96.3 kilograms).
Conclusions:
In our institutional experience, nearly half of patients starting long term ADT have significant fracture risk warranting further risk stratification and risk mitigation strategies. This baseline data should inform systematic approaches to select those that do—and do not—require bisphosphonate or denosumab in the hormone sensitive setting.
Impact of adherence to a remote exercise program on health-related quality of life in prostate cancer patients undergoing treatment: A prospective study in Brazil.
Authors: Bergerot Paulo Gustavo , Bergerot Cristiane Decat , Silva Jonas Ribeiro Gomes , Franca Marcos V S , Lages Dr. Paulo Sergio , Fuzita William Hiromi , Soto Pérez de Celis Enrique , Florez Narjust , Schmitz Kathryn H. , Pal Sumanta Kumar
Published: February 2025

130

Background:
Patients with metastatic prostate cancer (mPCa) undergoing treatment often experience declines in health-related quality of life (HRQoL) and increased symptom burden. Exercise interventions are known to mitigate these effects, but adherence to such programs remains a challenge. This study aimed to assess the impact of adherence to a remote, home-based exercise program on HRQoL and symptom burden among patients with mPCa in a joint cancer practice in Brazil.
Methods:
This prospective study recruited patients with mPCa undergoing active treatment for both hormone sensitive and hormone resistant disease. Patients were assessed at baseline (T1) and after 12 weeks (T2) using the Functional Assessment of Cancer Therapy-General (FACT-G; scale: 0-108) and the Edmonton Symptom Assessment System (ESAS; scale: 0-90). Eligible participants received weekly exercise guidance through WhatsApp and performed prescribed exercise regimens (3 to 5 hours per week of combined resistance and aerobic training), with proper techniques demonstrated using the Vedius platform. Adherence was categorized as moderate to high (MH) ≥6 weeks of exercise, or low (L) ≤5 weeks. The primary outcomes included changes in HRQoL and symptom burden.
Results:
A total of 35 patients were recruited. The median age of participants was 74 years (range 58-91), with a majority being white (65.7%), married (82.9%), highly educated (88.6%), and retired (85.7%). All patients were receiving ADT plus abiraterone (34.3%), or docetaxel (25.7%), or enzalutamide (22.8%), or chemotherapy + abiraterone (14.3%). At 12 weeks, patients with moderate to high adherence demonstrated significant improvements in HRQoL (MH Mean
T2
=94.9, L Mean
T2
=88.7, P=0.01), particularly in physical (MH Mean
T2
=25.1, Mean
T2
=23.6, P=0.03), functional (MH Mean
T2
=22.8, L Mean
T2
=20.7, P=0.03), and emotional (MH Mean
T2
=22.2, L Mean
T2
=20.28, P=0.03) well-being domains, compared to those with low adherence. Additionally, those with higher adherence reported a lower symptom burden (MH Mean
T2
=9.1 vs L Mean
T2
=14.7, P=01).
Conclusions:
This study demonstrates that adherence to a remote exercise program significantly improves HRQoL and reduces symptom burden in patients with prostate cancer undergoing treatment. These findings underscore the importance of promoting exercise adherence through accessible platforms, such as WhatsApp, to enhance patient outcomes in mPCa.
Association of statin use with overall survival and cardiac adverse events in patients with advanced prostate cancer treated with apalutamide: A pooled analysis of TITAN and SPARTAN.
Authors: Ozay Zeynep Irem , Morgan Scott C. , Chi Kim N. , Small Eric J. , Malone Shawn , Wallis Christopher J.D. , Ong Michael , Kishan Amar Upadhyaya , Jia Angela Y , Zaorsky Nicholas George , Swami Umang , Sun Yilun , Spratt Daniel Eidelberg , Chowdhury Simon , Agarwal Neeraj , Saad Fred , Roy Soumyajit
Published: February 2025

137

Background:
The impact of statins on overall survival (OS) in patients (pts) with advanced prostate cancer is not fully understood. We performed a pooled analysis of the TITAN and SPARTAN trials to determine if exposure to statins had an independent effect on OS and grade ≥3 cardiac adverse events (AE) in pts treated with androgen deprivation therapy (ADT) with/without apalutamide (APA).
Methods:
TITAN and SPARTAN randomized pts to receive ADT with/without APA either in metastatic hormone-sensitive or in non-metastatic castration-resistant prostate cancer, respectively. Pts had at least some duration of statin exposure during the assigned treatment which could have started before and ended during or after the assigned treatment. A stratified (for the trial) multivariable Cox proportional hazard model was applied to determine the association of statin use with OS. Adjusted (adj) OS was estimated for pts in each trial, separately. A multivariable stratified logistic regression model was applied to determine the association of statin exposure with grade ≥3 cardiac AE.
Results:
Out of 2190 pts included in this study, 1288 received APA (TITAN 517; SPARTAN 771) and 484 were exposed to statins. Statin exposure was associated with significantly superior OS among all APA-treated pts (adjusted hazard ratio [HR]: 0.58; 95% CI: 0.45-0.75) while the OS benefit was not significant among ADT-treated pts (adjusted HR: 0.83 [0.62-1.11]). Adjusted 3-year OS in pts with and without statins were 82% and 67% (adjusted difference: 15%; 95% CI: 6-24) in the APA arm of TITAN and 86% and 78% (adjusted difference: 8% [3-13]) in the APA arm of SPARTAN. Adjusted 3-year OS among pts with and without statins was 71% and 58% (adjusted difference: 13% [3-24]) in the ADT arm of TITAN and 77% and 75% (adjusted difference: -2% [-10 to 6]) in the ADT arm of SPARTAN. Statin exposure was associated with a higher risk of grade ≥3 cardiac AE in pts treated with APA (adjusted odds ratio [OR]: 2.92 [1.56-5.47]) and ADT (adjusted OR: 3.06 [1.18-7.89]).
Conclusions:
In this exploratory analysis, exposure to statins was associated with significantly improved OS in all APA-treated patients but not in ADT-treated patients. Statin exposure was also associated with a higher risk of grade ≥3 cardiac AE in all pts (APA and ADT), which could be attributed to pre-existing cardiac comorbidities requiring these patients to start statin.
Low-dose abiraterone in metastatic castration-resistant prostate cancer.
Authors: Lopes Julia Belone , Sanches Ana Elisa , De Menezes Dobbert Beatriz , Fernandez Fabio Leite Couto , Guedes João Daniel Cardoso , Netto João Pedro Homse , Ferreira Luiza , Forner Lorena , Araujo Daniel Vilarim
Published: February 2025

164

Background:
Abiraterone acetate (AA) is a selective and irreversible inhibitor of CYP17 approved for locally advanced and metastatic prostate cancer. The standard dose is 1000 mg orally while fasting. However, AA has a significant food effect, with serum levels increasing 5-7 times with a low-fat meal. Data suggest that a lower dose (250 mg with food, AALD) provides similar oncological outcomes to the standard dose, with a 75% cost reduction. In Brazil, 80% of patients are treated through the national public healthcare system, which does not afford AA in its label dose. Hospital de Base incorporated AALD since March 2021.Herein we present the data of patients with metastatic castration resistant prostate cancer treated with AALD.
Methods:
We retrospectively reviewed patients with mCRPC who received AALD at any treatment line, regardless of prior chemotherapy, from March 2021 to May 2023. The primary endpoint was PSA response rate (defined as a decrease of ≥ 50% in PSA concentration after 12 weeks of treatment). Secondary endpoints included time to treatment failure (TTF), overall survival (OS), and PSA response rate ≥ 50% at nadir. Data were summarized in medians, means and proportions. Chi-square was used for associations. Survival was calculated through Kaplan-Meier method. Cox-proportional hazards was used to compare groups. A p < 0.05 was considered statistically significant.
Results:
Ninety-six patients were included. The median age was 75 years (IQR 12.5), and most had an ECOG scoreof 1 (52.1%). Sixty-three patients (65.6%) received AALD in first-line, 26 (27.1%) in second-line, and 7 (7.3%) in third-line or beyond. The median PSA level before AALD was 20.9 (IQR 98.7). Twenty-seven patients (28.1%) had received docetaxel in mCRPC. After a median follow-up of 24.4 months, 53 patients (60.2%) had a ≥ 50% PSA response at 12 weeks, and 65 (69.9%) achieved a reduction of ≥ 50% at nadir. Patients treated with AALD pre-docetaxel had a higher PSA response at 12 weeks (68.3% vs. 40%, p = 0.015) and at nadir (76.1% vs. 53.8%, p = 0.036). First-line AALD was associated with better PSA responses. The median TTF was 7.9 months (5.5 – 10.3), and the median OS was 20.6 months (14.1 – 26). Achieving a ≥ 50% PSA response at 12 weeks was associated with improved TTF (13.6 vs. 4.6 months, HR = 0.37, p < 0.001) and OS (28.9 vs. 12.2 months, HR = 0.44, p = 0.004).
Conclusions:
AALD showed meaningful efficacy and survival outcomes. We advocate for AALD, particularly in settings where the standard dose is not affordable.
Time to metastasis after prostatectomy (TTM) and survival outcomes in patients (pts) with metachronous metastatic hormone-sensitive prostate cancer (mHSPC): A secondary analysis of the SWOG 1216 phase 3 trial.
Authors: Sayegh Nicolas , Jo Yeonjung , Swami Umang , Hage Chehade Chadi , Ozay Zeynep Irem , Gebrael Georges , Maughan Benjamin L. , Plets Melissa , Hussain Maha H. A. , Dorff Tanya B. , Lara Primo N , Goldkorn Amir , Lerner Seth P. , Agarwal Neeraj
Published: February 2025

173

Background:
It is well-established that pts with de-novo mHSPC have poorer survival compared to those with metachronous disease. However, the impact of timing of metastatic recurrence after definitive therapy on survival has not been extensively evaluated in pts with mHSPC. Therefore, we assessed the prognostic value of TTM using the SWOG 1216 trial data which randomized pts with mHSPC to androgen deprivation therapy (ADT) with orteronel (ORT) or bicalutamide (bic) (NCT01809691).
Methods:
Eligibility: Only pts with metachronous mHSPC who underwent prostatectomy were included in the analysis. Metachronous disease was defined as no evidence of metastasis within 90 days of initial prostate cancer diagnosis. TTM was defined from the time of prostatectomy to the time of initial metastatic diagnosis and was analyzed as a continuous variable, then categorized. Multivariable analyses for progression-free survival (PFS) and overall survival (OS) were performed using a Cox proportional hazards model, adjusting for treatment arm, disease burden, Gleason score, performance status, log-transformed PSA, and age.
Results:
Of the 1279 study participants, 301 underwent prostatectomy and had metachronous mHSPC, of whom 161 were in the experimental arm and 140 in the control arm. In the overall cohort, a longer TTM was not associated with improved PFS (HR 1.0, P=0.3) and OS (HR 1.0, P=0.14). Similarly, after stratification of TTM using 1, 2, 3, and 4 year-thresholds, there was no association with PFS and OS. Results remained comparable in the subgroups of pts receiving ADT + bic and ADT + ORT separately (Table).
Conclusions:
The timing of metastatic disease after prostatectomy in pts with metachronous mHSPC did not appear to be related to survival and should not be used as a prognostic factor nor to predict treatment outcomes.

ADT + ORT
ADT
Overall

HR (P-value)

PFS

OS

PFS

OS

PFS

OS

TTM Continuous
1.0 (0.8)
1.0 (0.8)
1.0 (0.3)
1.0 (0.1)
1.0 (0.3)
1.0 ( 0.1)

TTM <1 vs ≥1
1.1 (0.8)
1.4 (0.5)
0.9 (0.9)
1.7 (0.2)
1.1 (0.8)
1.6 (0.1)

TTM <2 vs ≥2
1.1 (0.7)
1.6 (0.3)
1.1 (0.6)
1.9 (0.1)
1.2 (0.3)
1.8 (0.04)

TTM <3 vs ≥3
1.1 (0.7)
1.4 (0.4)
1.5 (0.1)
1.7 (0.1)
1.4 (0.08)
1.6 (0.09)

TTM <4 vs ≥4
0.9 (0.8)
0.9 (0.9)
1.7 (0.03)
1.4 (0.4)
1.5 (0.05)
1.3 (0.4)
Efficacy and safety of ifosfamide and mesna in metastatic castration-resistant prostate cancer after taxane-based chemotherapy and novel hormonal therapy failure.
Authors: Kim Chang Gon , Ko Yeo Gyeong , Yoon Jongjin , Lee Chung , Beom Seung-Hoon , Choi Young Deuk , Han Woong Kyu , Ham Won Sik , Han Hyunho , Lee Jongsoo , Heo Ji Eun , Kim Daeseong , Baek Eunsil , Kim Sang Woo , Jung Minsun , Shin Sang Joon
Published: February 2025

174

Background:
Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789).
Methods:
Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m2 and mesna 1,500 mg/m2 on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by >50% (PSA50) or >90% (PSA90), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed.
Results:
A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range: 3–7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA50 and PSA90 were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS.
Conclusions:
Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC, warranting further investigation. Clinical trial information:
NCT06236789
.