bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of constellation virtual community atmosphere on blogger trust and constellation infatuation behavior
Authors: Li Qingxia , Li Shuang , Li Qiang , Li Yingji
Published: February 2025

With the rapid development of social media, astrology-related virtual communities have gained significant popularity in China. However, the mechanisms behind the formation of astrological addiction behaviors within virtual communities remain largely unexplored. This study, based on the Stimulus-Organism-Response (S-O-R) theory, investigates how community environmental characteristics and user traits influence astrological addiction through the mediation of blogger trust. The results show that both community atmosphere (CA) and community expertise (PK) significantly influence constellation infatuation (CI) through the mediation of blogger trust (BT). Specifically, community atmosphere and community expertise positively affect constellation infatuation through blogger trust, supporting the proposed hypotheses. However, online participation (NI) does not have a significant indirect effect on constellation infatuation via blogger trust. The findings suggest that blogger trust plays a critical role in shaping astrological addiction behaviors within virtual communities. This study offers theoretical insights into community management and contributes to understanding the dynamics of addictive behaviors in online environments.
Sepsis-induced cardiac dysfunction: mitochondria and energy metabolism
Authors: Yu Xueting , Gao Jie , Zhang Chunxiang
Published: February 2025

Sepsis is a life-threatening multi-organ dysfunction syndrome caused by dysregulated host response to infection, posing a significant global healthcare challenge. Sepsis-induced myocardial dysfunction (SIMD) is a common complication of sepsis, significantly increasing mortality due to its high energy demands and low compensatory reserves. The substantial mitochondrial damage rather than cell apoptosis in SIMD suggests disrupted cardiac energy metabolism as a crucial pathophysiological mechanism. Therefore, we systematically reviewed the mechanisms underlying energy metabolism dysfunction in SIMD, including alterations in myocardial cell energy metabolism substrates, excitation–contraction coupling processes, mitochondrial dysfunction, and mitochondrial autophagy and biogenesis, summarizing potential therapeutic targets within them.
A summer in the greater Paris: trophic status of peri-urban lakes shapes prokaryotic community structure and functional potential
Authors: Foucault Pierre , Halary Sébastien , Duval Charlotte , Goto Midoli , Marie Benjamin , Hamlaoui Sahima , Jardillier Ludwig , Lamy Dominique , Lance Emilie , Raimbault Emmanuelle , Allouti Fayçal , Troussellier Marc , Bernard Cécile , Leloup Julie , Duperron Sébastien
Published: February 2025

With more than 12 million inhabitants, the Greater Paris offers a “natural laboratory” to explore the effects of eutrophication on freshwater lake’s microbiomes within a relative restricted area (~ 70 km radius). Here, a 4-months survey was carried out during summertime to monitor planktonic microbial communities of nine lakes located around Paris (Île-de-France, France) of comparable morphologies, yet distinct trophic statuses from mesotrophic to hypereutrophic. By thus minimizing the confounding factors, we investigated how trophic status could influence prokaryotic community structures (16S rRNA gene sequencing) and functions (shotgun metagenomics). These freshwater lakes harbored highly distinct and diverse prokaryotic communities, and their trophic status appears as the main driver explaining both differences in community structure and functional potential. Although their gene pool was quite stable and shared among lakes, taxonomical and functional changes were correlated. According to trophic status, differences in phosphorus metabolism-related genes were highlighted among the relevant functions involved in the biogeochemical cycles. Overall, hypereutrophic lakes microbiomes displayed the highest contrast and heterogeneity over time, suggesting a specific microbial regime shift compared to eutrophic and mesotrophic lakes.
Migration aspirations and their realisation: a configurational driver analysis of 26 African and Asian research areas
Authors: Czaika Mathias , Weisner Zina
Published: February 2025

‘Tackling the root causes’ of migration has emerged as a central strategy for the European Union to manage the movements of people from middle- or low-income countries. While the effectiveness of this approach remains a subject of debate, the field of migration studies has highlighted the interplay of multiple migration drivers, or driver complexes, rather than singled out'root causes'. However, empirical research has yet to assess the specific configurations and interactions of these driver complexes across diverse emigration contexts, and also, whether policy interventions have any impact in reducing migration aspirations and actual emigration. This paper employs Qualitative Comparative Analysis (QCA) to assess the complexities surrounding migration aspirations and realizations in 26 research areas spanning ten African and Asian countries. Following the two-step model of migration, the study identifies necessary and sufficient conditions explaining regional disparities in emigration aspirations and intensity. The analysis explores how structural hardships such as poverty, poor livelihoods, insecurity, conflict, weak governance, and environmental stress interact with socio-cultural factors such as transnational ties and cultures of migration. We find that such hardships alone are not necessary or sufficient for driving migration aspirations or actual out-migration. Migration aspirations are influenced by a complex interplay of socio-cultural and political-economic factors. Within this dynamic, both migration networks and international ties as well as the relative absence of migration-discouraging policies play central roles. At the same time, even a deeply rooted culture of migration and strong migration aspirations are per se not sufficient in generating high levels of out-migration.
Caliper verification and gap measurements of kinematic alignment total knee arthroplasty utilizing an imageless, accelerometer-based navigation system
Authors: Sikes James H. , Melancon Drew P. , Spears Isaac J. , Powers Evan H. , Montgomery Spencer J.
Published: February 2025

Purpose

Kinematic alignment (KA) in total knee arthroplasty (TKA) aims to restore the patient’s knee to the prearthritic state. The purpose of this study was to investigate the accuracy of using an implant-agnostic, imageless, accelerometer-based navigation system to perform KA TKA on the basis of caliper verification and quantification of the flexion and extension gaps.

Materials and methods

Seven cadaveric lower extremities underwent primary TKA utilizing a kinematic alignment workflow with the imageless navigation system. Accuracy of the technique was confirmed through caliper verification of bone cuts.

Results

All cuts were within 1 mm of anticipated measurements, except for the lateral tibial fragment, which averaged 1 mm (standard deviation [SD] 0.9 mm) thicker than anticipated. In extension, medial and lateral gaps were symmetric and averaged within 0.6 mm of expectation. In flexion, the medial gap averaged within 0.5 mm of expectation, while the lateral gap averaged 2.6 mm larger than the symmetric expectation, consistently producing a trapezoidal space.

Conclusions

The implementation of an accelerometer-based navigation system in KA TKA allows for highly accurate results, which was confirmed with caliper verification. This workflow produced a symmetric extension gap and a trapezoidal flexion gap with an average increased lateral flexion gap of 2.6 mm compared with the medial side.
War for talent or even enemy at the gate? Investigating the role of employer brand experience in talent retention
Authors: Azimi Mohammad , Sadeghvaziri Faraz , Ebrahimi Elham , Mozafari Amin
Published: February 2025

Employer Branding is a crucial strategy for attracting and retaining talent within an organization. This concept has garnered significant attention from scholars and practitioners, resulting in various conceptualizations of employer branding elements. Despite this interest, the field remains relatively underdeveloped, and aspects such as employer brand experience require further exploration. This study contributes to the growing body of employer branding research by clarifying the role of employer brand experience and its relationship with concepts such as employer brand personality, employer brand identification, and talent retention. Data were collected from the Special Forces officers of the Iranian National Army and analyzed using the partial least squares method. The results indicate that employer brand experience and employer brand personality have a direct, significant impact on talent retention. However, while employer brand identification's effect on talent retention is positive, it was not found to be significant. The findings provide practical implications for organizations, suggesting they can better position their employer brand by focusing on employer brand experience and aligning their employer brand personality with talent management strategies.
Assessing the clinical impact of tumor volume on response to
177
Lu-PSMA radioligand therapy in metastatic castration-resistant prostate cancer.
Authors: Nikanpour Yalda , Ahmed Mohamed E. , Day Carter A , Mahon Mindie L , Haloi Rimki , Wael Zeina , Kwon Eugene D. , Andrews Jack
Published: February 2025

175

Background:
177
Lu-PSMA-617, a PSMA-directed radionuclide therapy, is an emerging treatment for metastatic castration-resistant prostate cancer (mCRPC). This retrospective study evaluates clinical outcomes of
177
Lu-PSMA-617 in low volume (LV) and high volume (HV) mCRPC, classified using the CHAARTED criteria.
Methods:
We conducted a retrospective review of the Mayo Clinic Prostate Cancer Registry, including mCRPC patients treated with
177
Lu-PSMA-617 at Mayo Clinic Rochester, MN, from August 2017 to August 2024. Patients were categorized based on CHAARTED criteria, which define high-volume disease by the presence of visceral metastases and/or four or more bone metastases, with at least one outside the vertebral column and pelvis. PSA-response rate (PSA-RR), overall survival (OS), PSA-progression-free survival (PSA-PFS), and radiographic progression-free survival (rPFS) were analyzed using Kaplan-Meier curves with log-rank tests, as well as uni- and multivariate Cox regression.
Results:
Of the 264 patients treated with
177
Lu-PSMA-617, 83 were classified as LV (median follow-up: 17.1 months) and 177 as HV (median follow-up: 13.7 months). LV patients had lower serum PSA levels (P < 0.0001), higher hemoglobin levels (P < 0.0001), and a longer time from diagnosis to treatment initiation (10.3 years vs. 7.2 years, P = 0.04). In the HV group, 92% had bone metastases, 60% had lymph node involvement, 54% had both, and 35% had visceral metastases. In the LV group, 64% had bone metastases, 84% had lymph node involvement, 25% had both, and none had visceral metastases. Median OS was 14.4 months for HV patients and 17.6 months for LV patients (P < 0.0001). Median PSA-PFS was 11.4 months for HV patients and 13 months for LV patients. Median rPFS was 9.1 months for HV patients and 10.6 months for LV patients. PSA-RR significantly differed between groups (P < 0.0001). In the HV group, 20% achieved CR (PSA < 0.2 ng/mL), 29% had PR (PSA decreased by ≥50%), 16% experienced SD, and 35% had PD (PSA increased ≥25% from nadir). In contrast, the LV group had 51% achieving CR, 10% achieving PR, 18% with SD, and 11% with PD.
Conclusions:
Lower disease volume in mCRPC is strongly associated with improved outcomes following
177
Lu-PSMA-617 therapy. These findings suggest that tumor burden is a key predictor of response to PSMA radioligand therapy.
Radium 223 without androgen deprivation therapy (ADT) in patients (Pts) with biochemically recurrent prostate cancer (BCR) and PET findings in the bones.
Authors: Abel Melissa Lauren , Karzai Fatima , Arlen Philip M. , Chen Clara , Mena Esther , Lindenberg Liza , Aragon-Ching Jeanny B. , Cordes Lisa M. , Lee-Wisdom Katherine , Hankin Amy , Williams Monique , McKinney Yolanda L , Gulley James L , Figg William Douglas , Choyke Peter , Madan Ravi Amrit
Published: February 2025

180

Background:
BCR pts have a rising PSA after definitive surgery or radiation, but negative CT/Tc99 scans. While ADT-based strategies are commonly used, they can be associated with life-altering toxicities and have not been shown to improve survival. Radium 223 is an alpha-emitting radiopharmaceutical that accumulates in areas of high bone turnover and has demonstrated a survival benefit in metastatic prostate cancer, but its benefits as a monotherapy in BCR without ADT have not been explored prior to this study. This strategy may be important as bone metastasis drives morbidity/mortality in prostate cancer.
Methods:
Eligible pts in this study (NCT04206319) have BCR following definitive therapy, testosterone (T) >100ng/dL, normal organ and marrow function, and negative CT/Tc99 imaging. Pts must have findings on a NaF or PSMA PET suspicious for metastatic bone disease not seen on Tc99. Pts are treated with Radium 223 at the approved dosing of 55 kBq/kg for 6 cycles. PSA declines were defined as 2 or more confirmed declines from an intra-study apex PSA (ISAP; Madan ASCO GU 2018). All pts have pre- and post-treatment PSMA and NaF imaging. Immune responses (primary endpoint) are to be evaluated at study completion.
Results:
18 pts have enrolled with 16 currently evaluable for response, with a median age of 67 yrs (58-80) and PSA of 1.75 ng/ml (0.2-49.5). 14/16 pts had PSMA+ scans. 13/16 pts had NaF+ scans. There have been no missed cycles for toxicity and no grade >3 toxicities. Grade 2 toxicities have been rare and no Grade 1 or 2 changes in hemoglobin or platelets have occurred. 2 pts with rapid PSA doubling times came off for progression and were not evaluable for follow up imaging. Five pts (31%) had confirmed ISAP PSA declines of 14%, 21%, 24%, 33%, and 57% lasting 84, 173, 292, 246+, and 661+ days, respectively. 8/11 evaluable pts had evidence of decreased standard uptake value (SUV) on NaF PET imaging after treatment. Two pts had resolution of multiple PSMA+ bone findings, and one of them remains with negative bone findings on PET after 2+ years and with a stable PSA.
Conclusions:
Radium 223 in BCR is safe and associated with rare grade 1/2 toxicities. Decreases in SUV seen on most NaF scans suggest Radium 223 targeting of suspicious lesions. Substantial improvements in PSMA imaging have been observed. Delayed but confirmed PSA declines have been seen in 31% of pts. Radium 223 monotherapy may have a therapeutic activity in BCR and further studies are needed to define its potential role in PET+ BCR. Clinical trial information:
NCT04206319
.
Genome-wide burden survival tests for patients with metastatic prostate cancer on androgen receptor-targeted therapies in the Million Veterans Program dataset.
Authors: Candelieri-Surette Danielle , Berlowitz Dan , Nelson Tyler , Carter Hannah , Rose Brent S , McKay Rana R. , Vassy Jason , Hauger Richard , Lynch Julie Ann , Teerlink Craig
Published: February 2025

251

Background:
Literature suggests various genes influence metabolism and treatment response in prostate cancer. While the androgen receptor gene is the primary target for hormonal treatment, studies increasingly highlight the roles of genes in lipid metabolism and pharmacogenetics, including
APOE, BGN, AHSG, CYP2D6, SLC2A4
, and
HSD3B1
. Genes allowing androgens to enter cells more efficiently may increase therapy resistance, worsening outcomes in recurrent or metastatic disease. An understanding of biomarkers and resistance mechanisms is essential to address this issue. We conducted a genome-wide search for genes that exhibit an effect on survival in patients on androgen receptor-targeted therapies.
Methods:
We developed two models: Model 1 identified 5,107 patients with metastatic prostate cancer receiving androgen deprivation therapy; model 2 focused on a subgroup 2,240 patients on abiraterone. We performed 18,544 distinct gene-level tests across the human genome using all coding variants within each gene, analyzing rare (minor allele frequency <1%) loss-of-function variants, and rare loss-of-function and missense variants. All analyses used the Veterans Administration’s Million Veterans Program (MVP) whole genome Release2 genomic data (96K males). We conducted separate analyses for African and European ancestry subjects. Gene-level survival analysis was performed using the SeqMeta R package that performs burden, Skat, and Skat-O tests. A Bonferroni correction was applied for 82,567 tests, requiring p<6.06E-7 to establish significance and p<5.00E-6 for suggestive evidence. Individual survival analyses were conducted on all SNPs within each significant gene.
Results:
Gene-level tests identified
OR1G1
(burden p=1.87E-7, OR=0.17),
PCDHGB1
(burden p= 2.92E-07, OR=0.61) and
CLPB
(burden p=3.34E-07, OR=0.30) as significantly associated with prostate cancer survival, while
SNX18
demonstrated a suggestive association (Skat-O p=3.40E-6) among European ancestry subjects in model 1. Among African ancestry subjects, the best performing gene was
UBD
(burden p= 2.61E-06, OR=0.76). Analyses of rare loss-of-function and loss-of-function or missense variants failed to achieve significant or suggestive evidence. Model 2 did not reveal any significant findings. Additional variant level survival analyses revealed 4 significant SNPs from
UBD
including chr6.29555893.C.A, chr6.29556082.G.C, chr6.29556095.A.G_A, chr6.29556226.A.G_A (1 copy HR 3.1, 2 copies HR 3.7, p <.05) and SNP chr5.54519665.A.C_A from gene
SNX18
(1 copy HR 1.5 p <.05).
Conclusions:
Our results indicate variants within several genes may influence prostate cancer survival by causing resistance to androgen-receptor targeted therapies and warrant follow-up in external datasets for validation.
Prognostic value of quantitative PSMA-PET parameters during chemotherapy in prostate cancer.
Authors: Skawran Stephan , Gafita Andrei , Lorenzini Theo , Hoberück Sebastian , Mattana Francesco , Di Giorgio Andrea , Miederer Matthias , Paller Channing Judith , Djaileb Loic , Solnes Lilja B , Farolfi Andrea , Ceci Francesco , Eiber Matthias , Voter Andrew F
Published: February 2025

33

Background:
PSMA-PET/CT is increasingly being used to monitor chemotherapy in prostate cancer and shows promise for predicting outcomes and improving response evaluation. This retrospective study aimed to determine the prognostic value of quantitative tumor burden parameters derived from PSMA-PET/CT for overall survival (OS) during taxane-based chemotherapy.
Methods:
Databases from 6 institutions were screened for patients who underwent[
68
Ga]Ga-PSMA11-PET and serum PSA measurements at baseline and within three months after last taxane based chemotherapy dose. Tumor segmentation was performed using DeepPSMA software and PSMA-PET whole-body quantitative parameters were obtained: PSMA-positive tumor volume (PSMA-VOL) and maximum/average standardized uptake value (SUV
max
, SUV
mean
). Univariate Cox-regression analyses by hazard ratio (HR) with 95% confidence interval (CI) were used to evaluate association of whole-body quantitative PSMA parameters and PSA levels with OS. Harrell’s concordance index (C-index) was used to determine prognostic accuracy. Optimal cut points were determined by maximizing the log-rank statistic.
Results:
A total of 128 patients were included, of whom 62/128 (48%) had castration-sensitive prostate cancer and 66/128 (52%) castration-resistant prostate cancer. At baseline, PSMA-VOL numerically reached the highest prognostic value for OS (C-index: 0.88) followed by PSA (C-index: 0.80, p = 0.85), while the percentage change in PSA levels had the highest prognostic value during treatment (C-index: 0.94) significantly higher than percentage change in PSMA-VOL (C-index: 0.85, p = 0.02), (complete data shown in Table 1).
Conclusions:
Baseline and post-therapeutic PSMA-PET/CT quantitative parameters are prognostic for OS after taxane-based chemotherapy in prostate cancer. Baseline PSMA-VOL had the highest prognostic value for OS, while changes in PSA levels outperformed changes in quantitative PSMA-PET parameters during treatment.

Parameter
Cut point
HR (95% CI)
P-value
C-index (95% CI)

PSMA
vol
, baseline

> 28 ml
5.59 (2.77 – 11.27)
< 0.001
0.88 (0.81 – 0.96)

SUV
mean
, baseline

< 13.2
2.00 (0.96 – 4.15)
0.06
0.29 (0.13 – 0.45)

SUV
max
, baseline

> 71
2.18 (1.23 – 3.86)
0.007
0.69 (0.57 – 0.82)

PSA, baseline
> 3.9 ng/ml
3.53 (1.75 – 7.13)
< 0.001
0.80 (0.69 – 0.92)

PSMA
vol
, relative change

> -21 %
4.48 (2.80 – 7.17)
< 0.001
0.85 (0.78 – 0.91)

SUV
max
, relative change

> -70 %
2.42 (1.50 – 3.82)
< 0.001
0.76 (0.67 – 0.86)

SUV
mean
, relative change

> -44 %
5.98 (2.57 – 13.88)
< 0.001
0.85 (0.73 – 0.98)

PSA, relative change
> -97 %
7.03 (3.20 – 15.43)
< 0.001
0.94 (0.88 – 0.99)
Outcomes of high-risk prostate-specific antigen level during active surveillance with targeted and systematic prostate biopsy.
Authors: Millan Braden , Saini Jaskirat , Hwang Mitchell J. , Hesswani Charles , Blachman-Braun Ruben , Koller Christopher R , Nethala Daniel , Wood Brad , Turkbey Baris , Gurram Sandeep , Pinto Peter A.
Published: February 2025

343

Background:
National Comprehensive Cancer Network (NCCN) recommendations for very low to intermediate-risk prostate cancer (PCa) include active surveillance (AS). Patients who develop a prostate-specific antigen (PSA) level over 20 ng/mL during AS, however, are re-classified as NCCN high-risk and are recommended to undergo definitive management. In the past decade, the diagnostic accuracy for PCa has significantly improved with a combined approach to prostate biopsies (magnetic resonance imaging and ultrasound fusion targeting + systematic). This study aims to describe the outcomes of patients who continued AS following a PSA of 20 ng/mL or higher.
Methods:
Patient information and clinical data were obtained from a prospectively maintained database at the National Cancer Institute (NCT02594202). Patients on AS with a minimum of one subsequent combined biopsy (fusion + systematic) following a PSA of 20 ng/mL or higher were identified. Descriptive statistics were obtained using GraphPad Prism 10.1 (Boston, Massachusetts USA).
Results:
A total of 20 patients were identified, of whom 15 (67.7%) subsequently underwent definitive management. Patients had a median age of 72.0 [IQR 71-74.8] years, with a median of 13 [IQR 10-12] years on AS. In the continued AS cohort, the most recent PSA was below 20 ng/mL in two patients with a median of 22.9 ng/mL [IQR 15.2 -23.6], while repeat biopsy showed benign tissue or grade group (GG) 1 disease. In those who underwent definitive management, the last PSA on AS was a median of 23.2 ng/mL [IQR 21.9-32.8], with all patients having GG 2 or higher disease. Twelve patients underwent surgery and three external beam radiotherapy with long-term androgen deprivation therapy, within a median time of 2 mos [IQR 2.0 - 2.5 mos] after their last biopsy. For those who underwent surgery, 4 (33.3%) had GG upstaging, 2 (16.7%) had GG downstaging, while 6 (50.0%) had no change in overall GG on final pathology. The first post-operative PSA was undetectable in all but one patient.
Conclusions:
A PSA greater than 20 ng/mL is a high-risk feature that continues to have clinical significance during AS in the contemporary era of combined prostate biopsies. In our small cohort, one quarter of the patients remain on AS, while three-quarters of the patients underwent definitive management. GG upgrading occurred in one third of patients and therefore continued AS in these patients should be approached with caution and limited to those with benign findings or GG 1 disease on follow-up combined biopsy.
Targeting highly aggressive ductal prostate tumours with poly ADP ribose polymerase inhibitor (PARPi) and androgen receptor signaling inhibitor (ARSi) combination therapy.
Authors: Ranasinghe Weranja , Delavar Mahsa , Lawrence Mitchell G. , Choo Nicholas , Niranjan Birunthi , Papagiris Melissa , Kraska Jenna , Wang Hong , Keerthikumar Shivakumar , Manyam Ganiraju C. , Troncoso Patricia , Shephard Peter S , Thompson Timothy C. , Taylor Renea , Chapin Brian Francis , Risbridger Gail
Published: February 2025

420

Background:
Prostatic ductal adenocarcinoma (DAC) is an aggressive prostate cancer variant, prone to early metastasis at low PSA levels and showing poor response to androgen blockade despite androgen receptor expression. Although DACs do not have any efficacious therapies, DACs frequently harbour DNA damage repair (DDR) mutations. We investigate the efficacy of combined PARP inhibitor (PARPi) and androgen signalling inhibitor (ARSi) therapy in DDR-proficient DAC tumours.
Methods:
To model DAC, organoids were developed in Matrigel from patient-derived xenografts (PDXs) originating from DDR-proficient radical prostatectomy (287R, 275R) and
BRCA2
heterozygous mutant metastatic (201.1) tumours, retaining key histologic and genomic features. These organoids were exposed to different PARP inhibitors (Talazoparib, Saruparib) and androgen signalling inhibitors (Enzalutamide, Apalutamide, Darolutamide) for up to 11 days. Cell viability and growth responses were assessed using PrestoBlue and CellTiter-Glo assays and automated imaging analysis. SynergyFinder software calculated synergy scores for each treatment combination. Results were further validated
in vivo
using DDR-proficient 287R PDXs. Mechanistic insights were explored through RNA sequencing of 20 DAC and ten acinar radical prostatectomy samples, and four matched DAC and acinar PDXs, with γH2AX immunohistochemistry to examine DNA damage response.
Results:
Overall, PARPi/ARSi combination treatment significantly reduced organoid viability compared to PARPi alone or ARSi in DDR-proficient and heterozygous
BRCA2
-mutant DAC tumours. The levels of synergy were comparable regardless of which PARPi and ARSi agents were combined.
In vivo
results using DDR-proficient PDX 287R confirmed the efficacy of PARPi + ARSi combination by reducing tumour volume by 58% compared to control (
p
=0.0198) and by 40% versus PARPi alone (
p
= 0.0326). Mechanistically, RNA sequencing demonstrated upregulation of multiple DDR pathways in DACs compared to acinar prostate tumours, regardless of the DDR status. After treatment with PARPi + ARSI combination, there was an increase in γH2AX compared to the control in the DDR-proficient PDX 287R (mean 1.42 vs 0.5, p=0.0056), suggesting enhanced DNA damage may contribute to the efficacy of the combination treatment.
Conclusions:
Our results show that PARPi increases the efficacy of ARSi in DAC. This is notable given the poor response of DAC to AR-directed treatments and provides the rationale for a pre-planned phase 1/2 study.
Prevalence of germline variants of uncertain significance in DNA repair genes and their potential impact on prostate cancer outcomes following radical prostatectomy.
Authors: Chiarelli Giuseppe , Fasulo Vittorio , Buffi NicolòMaria , Garofano Giuseppe , Finocchiaro Alessio , Paciotti Marco , Avolio Pier Paolo , Cieri Miriam , Soldà Giulia , Colombo Piergiuseppe , Saita Alberto , Hurle Rodolfo , Maura Federica , Cavalli Pietro , Asselta Rosanna , Casale Paolo , Lughezzani Giovanni , Lazzeri Massimo
Published: February 2025

421

Background:
Pathogenic variants (PVs) in DNA repair genes (DRG) are linked to a higher risk of aggressive prostate cancer (PCa). Understanding and managing variants of uncertain significance (VUS), however, remains a challenge. This study investigates the prevalence of germline VUS in PCa patients and their potential link to prognosis following robot-assisted radical prostatectomy (RARP), aiming to enhance clinical management and risk stratification.
Methods:
This is part of an ongoing PCa screening project in the Italian population aimed at identifying men with a genetic predisposition (AIRC - Fondazione AIRC per la Ricerca sul Cancro, IG 2020 ID 25027). Germline DRG variants were identified in men with high-risk PCa or those aged <50 scheduled for RARP. After informed consent, blood samples were collected, and data on age, stage, PSA, ISUP grade, and family history were recorded. Genetic analysis used a multigene panel, classifying VUS and PVs per ACMG/AMP and IARC guidelines. Primary outcome: VUS prevalence; secondary: correlations between VUS and pathological status, biochemical recurrence (BCR), and need for adjuvant therapy.
Results:
A total of 138 men who underwent RARP were enrolled. The median age was 64 years (IQR 57–68). ISUP grade was 1–2 in 54.0% of patients and 3–5 in 46.0%. Family history of PCa was present in 55%. Median PSA was 7.5 ng/mL (IQR 3.3–9.4). DRG variants were identified in 41 men (29.7%), of whom 34 (82.9%) had VUS and 7 (17.1%) had PVs (3 BRCA2, 1 BRCA1, 2 PALB2, 1 CHEK2). VUS carriers were younger at diagnosis (median 62 vs. 64 years). 25.8% of VUS carriers were node-positive, compared to 13.5% of those with negative DRG (p > 0.05). BCR occurred in 24% of VUS patients vs. 18% of those without DRG variants at nearly 2.5 years of follow-up, but this difference was not statistically significant. No significant differences in ISUP grade or positive margin rates were observed.
Conclusions:
VUS germline mutations are common in PCa patients undergoing RARP. These mutations appear associated with worse outcomes. Study limitations include a single-center cohort, small sample size, and a predominantly European ancestry population.
Automated classification of treatment state of patients with prostate cancer from structured medical record data to help enhance care.
Authors: Boyajian Richard Nishan , Kowtoniuk Ashleigh , Hensley Alford Sharon , Kumar Tarun , Mahatma Shilpa , Solankar Pravin , Kumar Shrey , Nguyen Paul L.
Published: February 2025

427

Background:
The number of US prostate cancer (PCa) cases is projected to expand exponentially while the oncology workforce stagnates. The increase in clinic demand requires innovative technologic approaches for patient management. We are developing a process for automatically tracking patients across the care continuum which can flag patients overdue for follow-up, send alerts when patients recur, and thereby optimize clinic resources. In order to place patients into the correct care pathway, their disease status must be correctly classified, which is the focus of the current study.
Methods:
Clinician specialist input was used to define five mutually exclusive care states in PCa (newly diagnosed, active surveillance, active treatment, post-treatment surveillance, and metastatic). Using a variable set defined to classify each care state, decision tree modeling was applied to abstracted, de-identified data from 150 patients seen in the Dana-Farber/Brigham Cancer Center radiation oncology clinic between 5/14 and 8/14/2024 to validate model care state classification. Model output and a case summarization were presented in an interactive web-interface designed using user experience principles. Through a secure login, a provider accessed the data for each case and recorded if the care state assignment and case summary were accurate.
Results:
The concordance between the model classification and provider assignment was 100%. The model correctly sorted the care states of each of the patients, of which the distribution was 0% newly diagnosed, 1% active surveillance, 12% active treatment, 73% post-treatment surveillance, and 13% metastatic The interactive web interface included graphical and table views of PSA test values with automatic calculation of doubling time and velocity. In addition, treatment events (prostatectomy, radiation, hormone therapy) were overlaid on the PSA graph for easy clinical analysis. A treatment summary table provided a chronologic view for each patient.
Conclusions:
The care state assignment model was able to correctly classify the care state of all 150 patients in this cohort for which structured, provider abstracted data was available. The next steps in clinical implementation will be EMR integration, automatic record abstraction, and end-user testing. We have already begun work to automatically ingest and parse PCa records using natural language processing and expand the user interface to include a patient care journey map, generation of a pre-visit clinical note, and care optimization protocols. The goal is to provide a tool that will decrease time for case review and appointment preparation, give case prioritization alerts based on PSA testing results, and automatically monitor surveillance care compliance thus optimizing clinic resources while ensuring no patient is lost to follow-up.
The comparison of clinical utility between pan-cancer panel and PCa-specific panel for mCRPC.
Authors: Dong Baijun
Published: February 2025

47

Background:
To compare the diagnostic efficiency of pathogenic variants and the value for clinical decision making between a pan-cancer panel and a prostate cancer (PCa)-specific panel among patients with metastatic castration-resistant PCa (mCRPC).
Methods:
637 mCRPC patients underwent panel-based targeted gene sequencing (Cohort A), among which, 327 patients underwent genomic profiling with a PCa-specific panel of 50 genes and 310 patients with a pan-cancer panel of 672 genes. Furthermore, 56 patients in Cohort A received both panel-based targeted gene sequencing approaches at the same time (Cohort B). The comparisons of the diagnostic efficiencies of pathogenic variants and clinical actionable variants (CAVs) were analyzed by proportion test.
Results:
The diagnostic efficiency of pathogenic variants was significantly higher in pan-cancer panel group than in PCa-specific panel group either in cohort A or cohort B (p<0.0001). In cohort A, 504 of 970 genomic variants were defined as pathogenic variants among which 304 were classified as CAVs in PCa-specific panel group. In pan-cancer panel group, 1457 of 4205 genomic variants were defined as pathogenic variants among which only 304 were classified as CAVs. In cohort B, 96 of 182 genomic variants were defined as pathogenic variants among which 56 were classified as CAVs in PCa-specific panel group. In pan-cancer panel group, 260 of 788 genomic variants were defined as pathogenic variants among which only 59 were classified as CAVs. The detection rate of CAVs between the two groups was no difference either in cohort A or cohort B (p>0.05).
Conclusions:
The pan-cancer panel had increased detection yield of pathogenic variants and provided a rich source of data, which was helpful for genetic researches. However, the PCa-specific panel proved to be as powerful as the pan-cancer panel in the detection of CAVs for tailored treatments, which might be better in guiding clinical decision making in a cost-effectiveness and time-saving way. Thus, the NGS panels available in different sizes might be chosen depending on basic research or clinical objectives.
Impact of deferred cytoreductive nephrectomy in the era of the immunotherapy in metastatic renal cell carcinoma: A multicenter retrospective study.
Authors: Rioja Patricia , Passarella Carolina , Angel Martin , Valderrama Wbeimar , Bosma Freya , Anguera Georgia , Gomez Victoria , Ruiz-Granados Álvaro , Plata David , Zapata Laguado Martin Ignacio , Orta-Ruiz Alberto , Gandur-Quiroga Maria Natalia , Bourlon Maria T. , Grande Enrique , Manneh Ray , Molina-Cerrillo Javier , Maroto-Rey Pablo , Sade Juan Pablo , Castellano Daniel
Published: February 2025

502

Background:
Deferred cytoreductive nephrectomy (dCN) is an emerging, strategy in the management of metastatic renal cell carcinoma (mRCC), applied selectively to patients who demonstrate a favorable response to initial systemic therapy. This study aimed to assess the clinical impact of dCN within the context of sequential treatment management.
Methods:
A multi-institutional retrospective evaluation. The descriptive analysis was performed to examine the demographic and clinical characteristics. Progression-free survival (PFS) and overall survival (OS) were analyzed by the Kaplan-Meier method. A level of p < 0.05 was considered significant.
Results:
With a median follow-up of 19 months (1-174 months), 50 patients were divided into three groups: 46% received IO+TKI, 24% received IO+IO, and 30% received TKI. Of the cohort, 66% were male, with median age of 60.6 years. All had clear cell histology, and 76% were intermediate IMDC risk. The most common metastatic sites were lungs (50%), lymph nodes (36%), and bone (32%). The median time from systemic therapy to cytoreductive nephrectomy (CN) was 6 months. Notably, 26% did not restart treatment post-CN, and 6% discontinued pre-CN (two due to toxicity, one due to progression). Median PFS was 36 months, with a 5-year PFS rate of 40%. Analysis by IMDC risk and type of treatment showed no significant differences. However, patients with a Karnofsky score (KS) ≤80% had a lower risk of progression than those with KS >80% [HR: 0.31, 95% CI (0.13-0.75), p=0.01] and those achieving complete response had a significantly lower risk of progression [HR: 8.59, 95% CI (1.1-67), p=0.042]. Median OS was 91 months, with no significant differences between groups.
Conclusions:
This study demonstrates that dCN can offer a therapeutic advantage especially in selected patients who achieve favorable responses to upfront systemic therapy. Careful patient selection is crucial to maximize the potential benefits of delayed surgery, reduce perioperative risks and improve oncological outcomes. Larger patient cohorts and well-designed prospective clinical trials are essential to solidify these findings and establish evidence-based guidelines.
Real-world outcomes among patients with metastatic castration-resistant prostate cancer (mCRPC) receiving guideline-recommended therapies after treatment with
177
Lu-PSMA-617: A real-world prostate cancer disease observation (PRECISION) data platform analysis.
Authors: Wei Xiao X. , Shore Neal D. , George Daniel J. , Heath Elisabeth I. , Nguyen Jennifer , Patel Jeetvan , Sawhney Amrita , Kang Barinder , Byrne Clare , Tang Jackson , Sartor Alton Oliver
Published: February 2025

61

Background:
177
Lu-PSMA-617 was approved in March 2022 for patients with mCRPC pretreated with an androgen receptor pathway inhibitor (ARPI) and a taxane. There are limited data on the effectiveness of treatments post-
177
Lu-PSMA-617. The aim of this study was to describe prostate-specific antigen (PSA) responses among patients with mCRPC receiving a guideline-recommended therapy as the next therapy after
177
Lu-PSMA-617 treatment.
Methods:
This retrospective, observational study used real-world data from the PRECISION data platform, a proprietary dataset developed by Novartis, comprised of patient-level electronic health record and claims data that represent the US advanced prostate cancer population in the community, academic, urology, and medical oncology settings. Patients with mCRPC who received any guideline-recommended therapy at least 14 days after treatment with
177
Lu-PSMA-617 between March 23, 2022 and July 31, 2024 were included. Guideline-recommended therapies included abiraterone, enzalutamide, darolutamide, apalutamide, cabazitaxel, docetaxel, pembrolizumab, sipuleucel-T, niraparib, olaparib, talazoparib, rucaparib, and radium-223. Patients’ PSA values while on
177
Lu-PSMA-617 treatment were compared with their PSA values during the subsequent therapy course. Proportions of patients achieving reductions in PSA levels ≥50% (PSA50) and ≥80% (PSA80) were estimated. All analyses were descriptive.
Results:
A total of 152 patients receiving any subsequent guideline-recommended therapy after
177
Lu-PSMA-617 were identified. Mean age was 72.1 years. Most patients received an ARPI (n=93, 61.2%) – abiraterone (n=38), enzalutamide (n=37), darolutamide (n=10), or apalutamide (n=8) – as their subsequent therapy. Of patients who received a taxane (n=42, 27.6%), 24 received cabazitaxel and 18 received docetaxel. Median time to initiation of subsequent therapy was 206 days (interquartile range [IQR] 101–301 days) from
177
Lu-PSMA-617 initiation and 44 days (IQR 17–119 days) from
177
Lu-PSMA-617 discontinuation. Overall, among patients with sufficient information for PSA evaluation (n=30), 46.7% achieved PSA50 and 40.0% PSA80 post-
177
Lu-PSMA-617. Among patients receiving an ARPI, PSA50 was observed in 11/18 (61.1%) and PSA80 in 10/18 (55.6%). Among patients receiving a taxane, PSA50 and PSA80 were seen in 3/12 (25.0%) and 2/12 (16.7%), respectively.
Conclusions:
In this real-world analysis, the majority of patients who received guideline-recommended therapies after
177
Lu-PSMA-617 achieved at least a PSA50 response, suggesting that
177
Lu-PSMA-617 treatment does not preclude response to other subsequent therapies.
Paclitaxel, ifosfamide, cisplatin (TIP) in patients with advanced urethral adenocarcinoma: A single center, retrospective analysis.
Authors: Park Gwanhyun , Park Inkeun , Yoon Shinkyo , Lee Jae Lyun
Published: February 2025

656

Background:
Urethral adenocarcinoma (UA) is a very rare subtype of cancers arising in urethra, which is known for female predominance and poor prognosis. Rarity of UA impedes the conduction of prospective clinical trial, thus the treatment option for advanced UA is very limited. Usually platinum-based chemotherapy is given based on case reports. We conducted retrospective single center cohort review of TIP regimen in patients (pts) with locally advanced, recurrent or metastatic UA to evaluate its efficacy and safety.
Methods:
Clinical data of 18 pts with locally advanced, metastatic, or recurrent UA who received TIP regimen at the Department on Oncology, Asan Medical Center from Jul 2016 to Jan 2024 were collected. To be eligible, pts should have histologic confirmation of adenocarcinoma, adequate clinical information, and baseline and follow-up imaging test results. TIP regimen consists of paclitaxel 200 mg/m
2
over 3 hours intravenously (iv) on day 1 (D1), ifosfamide 1,500 mg/m
2
over 1 hour iv on D1-3 with mesna 300 mg/m
2
3 times a day iv on D1-3, and cisplatin 70 mg/m2 over 1 hour iv on D1. We recommended pegylated G-CSF for prevention of severe neutropenia and febrile neutropenia. The primary endpoint was objective response rate (ORR) according to RECIST v1.1, and secondary end points were progression-free survival (PFS), overall survival (OS), and toxicity.
Results:
A total of 18 pts were enrolled. All pts were female, and median age was 62 (range 43-74). Disease status was locally advanced (32%), recurrent (47%), and initially metastatic (16%), and ECOG PS were 0 (22%), 1 (72%), and 2 (6%). Most common site of metastasis were lymph nodes (50%), surgical bed (22%), lung (22%), and peritoneum (17%). Patients received TIP as 1
st
line (67%) and 2
nd
line (33%). Thirteen pts received prophylactic pegylated G-CSF. Median 4 cycles (range 1-6) of TIP were administered, and ORR was 44% (partial response 44%, stable disease 50%, and progressive disease 6%). With a median follow-up duration of 38.7 months, median PFS and OS were 7.0 months [95% confidence interval (CI) 3.8-10.2] and 40.0 months (15.6-63.7), respectively. Most common adverse events included anemia, peripheral neuropathy, anorexia, nausea, fatigue, neutropenia, thrombocytopenia. Most adverse events were manageable, and no unexpected toxicities were found.
Conclusions:
TIP showed promising efficacy in pts with advanced UA. TIP might be considered as one of treatment options for pts with advanced UA, although efficacy and safety should be validated in larger cohort.
Intravesical gemcitabine and docetaxel combined with intravenous tislelizumab as a durable strategy for high-risk non–muscle-invasive bladder cancer.
Authors: Chen Xiaobao , Wei Jiang , Xie Ruoyun , Zheng Huaiying
Published: February 2025

703

Background:
For decades, intravesical Bacillus Calmette-Guérin (BCG) has been the standard treatment for high-risk non-muscle-invasive bladder cancer (HR NMIBC). However, its poor tolerability and limited availability underscore the urgent need for more effective therapies. Intravesical sequential gemcitabine and docetaxel (GemDoce) has demonstrated efficacy in HR NMIBC, and immune checkpoint inhibitors (ICIs) have shown effectiveness as second-line therapy for patients with BCG-unresponsive NMIBC. Nevertheless, the combination of immunotherapy with intravesical GemDoce has not yet been reported.
Methods:
We retrospectively analyzed HR NMIBC patients, who received intravesical GemDoce combined with intravenous tislelizumab at Fujian Medical University Union Hospital from February 2023 to August 2024. Induction GemDoce was administered weekly for 6 weeks, then monthly maintenance. Tislelizumab started during the second GemDoce treatment and continued every 4 weeks. Inclusion required at least 6 weekly GemDoce after complete transurethral resection of bladder tumor (TURBT). Data including patient clinicopathologic features, treatment history, adverse events (AEs), and oncologic outcomes were retrospectively reviewed and analyzed.
Results:
30 patients included in study, with a median number of 16 (range:6-22) GemDoce treatments and 12 (range:2-18) tislelizumab cycles. Median age was 70 (range:49-80) years. All patients had papillary disease with or without CIS, including 11 (36.7%) with HGTa and 19 (63.3%) with HGT1. CIS with HGTa was present in 2 (6.7%) patients. 5 (16.7%) patients were BCG-naïve HR NMIBC, while 25 (83.3%) patients were recurrent HR NMIBC. Most patients were male (90%, 27/30), and 56.7% (17/30) had a smoking history. Treatment was well tolerated with no discontinuations or dose reductions. In total, 12 (40%) patients reported AEs following treatment, all of which were grade 1-2. Median follow-up of 11.5 (range:2-18) months, no patients had recurrence, underwent RC, or died.
Conclusions:
These results suggest that intravesical GemDoce with intravenous tislelizumab is an effective and tolerable treatment option for patients with HR NMIBC. Further prospective study is warranted.