bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of life in persons at risk for bipolar disorder: a two year prospective-longitudinal observational cohort study (BipoLife)
Authors: Glaus Johanna , Karow Anne , Lambert Martin , Sowada Pia , Bröckel-Bundt Kyra , Berndt Christina , Sauer Cathrin , Juckel Georg , Fallgatter Andreas J. , Bechdolf Andreas , Reif Andreas , Matura Silke , Kittel-Schneider Sarah , Stamm Thomas , Kircher Tilo , Falkenberg Irina , Jansen Andreas , Correll Christoph U. , Fusar-Poli Paolo , Bauer Michael , Pfennig Andrea , Rohenkohl Anja Christine
Published: February 2025

Background

Improving quality of life (QoL) is important for the treatment of people with bipolar disorder (BD). Early-BipoLife is a German multicentre naturalistic, prospective-longitudinal observational cohort study investigating early recognition and intervention in people at increased risk of developing a BD. This analysis aims to investigate influencing factors and changes in QoL as a basis for the development of early intervention strategies in patients with at risk syndrome for BD.

Method

A cohort of 1086 participants (15–35 years) with at least one risk factor (EPIbipolar criteria) for BD was assessed over the course of 2 years. Changes in QoL (WHOQOL-BREF) were evaluated in a mixed model for repeated measures.

Results

Compared to an age-matched comparison group, people at risk for BD showed significant lower QoL in all domains at baseline. The overall QoL of the psychological well-being domain of the WHOQOL-BREF increased over the 2 year study course (p < 0.001). The bipolar risk group (EPIbipolar) change from baseline divided into (a) decreasing, (b) increasing and (c) constant risk group in the course of 2 years. Baseline risk group assignment was not a significant predictor of change in QoL over 2 years for any of the QoL domains, but participants with an increase in risk over the 2-year course had a significantly smaller gain in QoL than the group with constant risk (p = 0.014) or decreasing risk (p < 0.001). Higher levels of QoL were associated with a higher self-rated ability to use coping strategies. Moreover, a higher level of functioning (GAF) at baseline was positively correlated with improvement of different QoL domains after 2 years.

Conclusion

Patients with a risk syndrome for BD reported significantly reduced QoL compared to their age-matched comparison group. Risk status monitoring might be beneficial to identify individuals who could profit from an intervention to increase their QoL. Further studies promoting the development of coping strategies for successful self-management could be helpful to improve overall mental health and positively influence QoL.
Intraindividual crossover comparison of gadobenate dimeglumine-enhanced and gadoxetate disodium-enhanced MRI for characterizing focal liver lesions
Authors: Tang Wenjie , Xiao Yuanqiang , Kuang Sichi , Rong Dailin , He Bingjun , Grazioli Luigi , Hussain Shahid M. , Wang Jin
Published: February 2025

Background

Gadobenate and gadoxetate are hepatobiliary magnetic resonance imaging (MRI) contrast agents. We intraindividually compared these two agents for the characterization of focal liver lesions (FLLs).

Methods

A total of 140 adult subjects were randomized to undergo two 3-T MRI exams separated by 7–14 days, one with 0.05 mmol/kg gadobenate and one with 0.025 mmol/kg gadoxetate. For both exams, we acquired the same unenhanced T1-weighted, T2-weighted, and diffusion-weighted sequences, followed by contrast-enhanced T1-weighted sequences during the dynamic and hepatobiliary phases (HBP) (at 20 min for gadoxetate, at 120 min for gadobenate). Three experienced unaffiliated readers independently evaluated each exam in blinded, randomized order for lesion nature (benign/malignant) and specific lesion diagnosis. McNemar test, Wald tests. paired t-tests and κ statistics were used.

Results

A total of 208 FLLs (108 malignant and 100 benign) were confirmed at final diagnosis. Sensitivity and specificity for malignant/benign differentiation ranged from 91.6% to 99.1% and from 87.5% to 90.5% for gadobenate, and from 86.0% to 91.6% and from 79.7% to 83.6% for gadoxetate. Significantly (p ≤ 0.025) higher values for gadobenate were determined for all diagnostic performance parameters except for sensitivity and negative predictive value for one reader. Significantly (p < 0.001) greater accuracy and confidence for specific lesion diagnosis was achieved with gadobenate for two of three blinded readers. Interreader agreement for malignant/benign differentiation was better with gadobenate (κ = 0.91 versus κ = 0.72).

Conclusion

Gadobenate was superior to gadoxetate for the differentiation and diagnosis of malignant and benign FLLs for two of three readers. Further confirmatory studies that include a wider representation of different types of FLLs are warranted.

Relevance statement

Better diagnostic performance and greater confidence in the characterization of FLLs with gadobenate might improve patient management decisions and timings, and potentially lead to better patient outcomes.

Key Points

Better diagnostic performance for the differentiation of FLLs was achieved with gadobenate for two of three readers.

Reader confidence for lesion diagnosis was greater with gadobenate.

Superior dynamic phase imaging with gadobenate was crucial for accurate lesion diagnosis.

Graphical Abstract
Pulmonary regional blood flow: validation of low-dose two-volume dynamic CT perfusion imaging in a swine model
Authors: Zhao Yixiao , Luu Nile , Hubbard Logan , Malkasian Shant , Molloi Sabee
Published: February 2025

Background

We aimed to validate a low-dose two-volume pulmonary computed tomography (CT) perfusion technique.

Methods

Five Yorkshire swine (weight 53.6 ± 2.6 kg) underwent 21 independent CT perfusion acquisitions. Intravenous contrast material (370 mg/mL iodine, 0.5 mL/kg) and saline chaser (0.5 mL/kg) were injected at 5 mL/s for each acquisition. Two-volume and multivolume dynamic CT perfusion data were acquired using a 320-slice CT, with multivolume measurements serving as the reference standard. The two-volume CT perfusion involved a low-dose (50 mA) volume scan before contrast injection and a diagnostic (300 mA) volume scan after bolus-tracking in the main pulmonary artery at the peak contrast enhancement. Multivolume CT perfusion included 15–20 volume scans for blood flow measurement. Paired sample t-test, linear regression, and Bland–Altman analysis compared both global and regional two-volume perfusion measurements to the reference standard. The reproducibility of the two-volume CT perfusion was assessed from two independent measurements under the same perfusion condition.

Results

Two-volume global perfusion measurements (P
2V) were related to reference multivolume (P
MV) measurements by P
2V = 0.96 × P
MV + 0.45 (r = 0.92), with a root-mean-square error of 1.29 mL/min/g and a root-mean-square deviation of 1.29 mL/min/g. The CT dose index for the two-volume and multivolume CT perfusion measurements were 9.3 mGy and 184.8 mGy, respectively.

Conclusion

We successfully validated a prospective, two-volume CT perfusion technique in a swine model. The findings affirm the feasibility of accurate and reproducible pulmonary blood flow measurement.

Relevance statement

This two-volume CT pulmonary perfusion technique, validated in a swine model, demonstrates the feasibility of blood flow measurement with a substantial reduction in radiation exposure. It could allow low-dose regional blood flow measurement in the assessment of pulmonary artery disease in humans.

Key Points

Lung perfusion can be measured in mL/min/g using a prospective, two-volume CT technique.

Flow measurement is achievable in a swine model with a radiation dose as low as 9.3 mGy.

CT angiography and perfusion can be acquired following a single contrast injection.

Graphical Abstract
Effectiveness and safety of transarterial chemoembolization combined with PD-1 inhibitors and lenvatinib for unresectable intrahepatic cholangiocarcinoma
Authors: Huang Jin-Tao , Hu Di , Hong Xin , Zhou Wen-Jie , Shen Jian , Lv Peng-Hua , Zhu Xiao-Li
Published: February 2025

Background

The objective of this study was to evaluate the therapeutic effectiveness and safety of transarterial chemoembolization (TACE) combined with programmed cell death-1 (PD-1) inhibitors and lenvatinib in the treatment of unresectable intrahepatic cholangiocarcinoma (uICC).

Methods

This multicenter retrospective study screened patients with uICC who underwent TACE in combination with PD-1 inhibitors and lenvatinib between January 2019 and June 2023. Tislelizumab or camrelizumab (200 mg) was intravenously administered every three weeks. The daily dose of lenvatinib was 8 mg for patients weighing < 60 kg and 12 mg for those weighing ≥ 60 kg. In cases of disease progression, the therapeutic strategy was adjusted based on the clinical condition and individual patient’s treatment preferences. Options included transitioning to standard or supportive care or continuing treatment with TACE in combination with PD-1 inhibitors and lenvatinib. The primary outcomes were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included the objective response rate (ORR), disease control rate (DCR), and the incidence of adverse events (AEs).

Results

A total of 59 patients with uICC were included. Over a median follow-up period of 32.3 months, the median OS and PFS were 25.8 months (95% confidence interval [CI]: 17.9–33.7) and 9.5 months (95% CI: 7.9–11.0), respectively. The ORR was 55.9%, and the DCR was 96.6%. Grade 3 or four AEs were observed in 15 of 59 patients (25.4%).

Conclusion

TACE combined with PD-1 inhibitors and lenvatinib demonstrated a promising therapeutic potential with a manageable safety profile for patients with uICC.

Relevance statement

The combination of TACE, PD-1 inhibitors, and lenvatinib represents a novel therapeutic option for patients with uICC.

Key Points

TACE plus PD-1 inhibitors and lenvatinib represent a promising therapeutic strategy for uICC.

The safety profile of TACE plus PD-1 inhibitors and lenvatinib was manageable.

This study demonstrated improved outcomes compared to prior standard-of-care treatments.

Graphical Abstract
Evaluation of usability, feasibility and acceptance of the digital training diary Trainingslog for individuals with axSpA: a mixed-method study
Authors: Pfyl Neva , Ettlin Lea , Niedermann Karin , Rausch Anne-Kathrin
Published: February 2025

Background

Physical activity (PA), including regular exercise, is essential for the successful management of axial spondyloarthritis (axSpA). To promote a physically active lifestyle, a digital training diary (Trainingslog) was developed in an user-centered approach by the Swiss Ankylosing Spondylitis Association (SVMB). A training diary promotes PA through feedback, goal setting and self-monitoring, which can also be used for PA counselling by physiotherapists (PT). Usability, feasibility and acceptance are essential for the successful implementation of a mobile Health Intervention such as the Trainingslog. The study objective is to evaluate the usability, feasibility and acceptance of the Trainingslog for individuals with axSpA and PTs.

Methods

A mixed-methods design was performed among potential end-users of the Trainingslog. Quantitative data was collected by use of questionnaires (System Usability Scale (SUS, 0-100 scale), user version of the Mobile App Rating Scale (uMARS, 5 point scale)) and number of training entries. Subsequently, qualitative data was gathered through semi-structured online focus groups or individual interviews.

Results

11 PTs (9 women, mean age 52.5 [SD 15.6]) and 10 individuals with axSpA (6 women, mean age 48 [SD 13.4]) participated. The quantitative data showed mean SUS scores for usability of 82.5 [SD 21.76] for PTs and 77.0 [SD 9.34] for individuals with axSpA. The mean uMARS sector B scores for feasibility were 4.2 [SD 0.49] for PTs and 4.1 [SD 0.38] for individuals with axSpA. Acceptance, as indicated by the uMARS results (mean score > 3 in Sectors E and F for both groups), was given. But there was a lower-than-expected agreement in the training entries, with 59.86% of entries matching between the Trainingslog and the paper diary. The qualitative analysis unveiled that while usability and feasibility were good, acceptance was lower, primarily due to the use of a web-based link instead of an app version.

Conclusion

The Trainingslog showed a good usability and feasibility, while the acceptance was lower than expected. Acceptance could be increased by offering the Trainingslog as an app-based version, along with implementing additional recommendations for enhancement. Consequently, the Trainingslog has the potential to be applied in PA counselling by PTs or as a self-monitoring tool for individuals with axSpA.
Enhanced adsorption of phenol using EDTA-4Na- and KOH-modified almond shell biochar
Authors: Chen Yanqin , Wang Donghui , Wang Xueli , Wu Jing , Song Shifang
Published: February 2025

To enhance the performance of biochar made from almond shells for adsorption of phenol pollutants in water, we prepared an almond shell-based biochar and modified it through combined pyrolysis with KOH and EDTA-4Na at 750 °C, yielding almond shell-based modified activated carbon (A-BC); the mass ratio of biochar, EDTA-4Na, and KOH was 1:1:3.

A-BC was characterized by using Scanning Electron Microscopy, Fourier Transform Infrared Spectroscopy, the Brunauer–Emmett–Teller method, and X-ray Diffraction. The adsorption conditions of A-BC for phenol were optimized through single-factor experiments, and the adsorption mechanism was explored through kinetics and thermodynamics assays. The results show that A-BC exhibits a honeycomb-like structure with a specific surface area of 1050 m2 g−1 and a micropore ratio of 86%. A-BC is rich in functional groups (-OH, -CH2, N–C, C-H, N–H) closely related to phenol adsorption. The adsorption of phenol by A-BC is a spontaneous exothermic process involving both physical adsorption and chemical adsorption (including hydrogen bonding and π-π interactions). The pseudo-second-order kinetic model adequately describes the adsorption process, which consists of liquid film diffusion, surface adsorption, and intraparticle diffusion stages. At 25 °C, with an A-BC dosage of 1.0 g L−1, initial phenol concentration of 400 mg L−1, and contact time of 60 min, A-BC exhibited significant adsorption capacities of 161 and 149 mg g−1 for simulated water and phenol-containing wastewater from coal chemical industries, respectively. A-BC demonstrated good reuse performance and strong adsorption capacity for phenol, indicating its potential application in treating phenol-containing wastewater from coal chemical industries.
Comparing perioperative outcomes in video-assisted thoracic surgery and robot-assisted thoracic surgery in lung cancer surgeries: a single-centre experience
Authors: Otorkpa Michael Joseph , Arif Salman , Gooseman Michael , Tentzeris Vasileios , Qadri Syed
Published: February 2025

Background

Lung cancer continues to be the primary cause of cancer-related deaths worldwide, with surgical resection recognised as the gold standard for non-small cell lung cancer. Recent innovations in thoracic surgery, including video-assisted thoracic surgery and robotic-assisted thoracic surgery, have revolutionised surgical methodologies. This study seeks to evaluate the perioperative outcomes of video-assisted thoracic surgery and robotic-assisted thoracic surgery in lung cancer procedures, concentrating on postoperative complications, length of hospital stay, and overall efficacy based on a single-centre experience.

Results

A total of 269 lung resections were conducted, with 176 (65.4%) completed using video-assisted thoracic surgery and 93 (34.6%) utilising robotic-assisted thoracic surgery. No notable disparities were observed in demographics or preoperative characteristics between the groups. The overall complication rates were 13.1% for video-assisted thoracic surgery and 16.1% for robotic-assisted thoracic surgery (p = 0.507). No substantial changes were observed in specific problems, such as air leaks and infections. The average postoperative duration was 3.26 days for video-assisted thoracic surgery and 3.70 days for robotic-assisted thoracic surgery (p = 0.252), with a 30-day mortality rate of 0.6% for video-assisted thoracic surgery and 0% for robotic-assisted thoracic surgery.

Conclusions

Video-assisted thoracic surgery and robotic-assisted thoracic surgery produce similar perioperative results in lung cancer procedures, showing no statistically significant differences in complications, length of hospital stay, or fatality rates. These findings correspond with the current literature, indicating that although robotic-assisted thoracic surgery may present specific benefits, the overall efficacy of both strategies is comparable. Future research using larger cohorts is crucial to gain a more in-depth understanding of these techniques and their long-term effects on patient outcomes.
Lentinula edodes mycelia extract abrogates chemotherapy-evoked cold and mechanical allodynia in mice
Authors: Tsubaki Masanobu , Kato Natsuki , Tateishi Keisuke , Yoshida Kengo , Matsuo Taira , Komori Rie , Morikawa Toshio , Nishida Shozo
Published: February 2025

Background

Chemotherapy-induced peripheral neuropathy (CIPN) is a detrimental outcome of various antineoplastic drugs, such as paclitaxel (PTX), vincristine (VCR), oxaliplatin (L-OHP), and bortezomib (BOR). CIPN results in pain and disability, thereby reducing quality of life and discontinuation of chemotherapy. Currently, the only effective treatment for CIPN is using duloxetine. Therefore, development of new treatments is necessary. Extract of Lentinula edodes mycelia (LEM) improves the quality of life for individuals undergoing chemotherapy treatment. As treatment with LEM may attenuate CIPN after chemotherapy, this study was conducted to determine whether treatment with LEM abrogates L-OHP-, PTX-, VCR-, and BOR-evoked cold and mechanical allodynia in mice.

Results

We found that LEM exhibits protective effects against cold and mechanical allodynia in mice treated with L-OHP, PTX, VCR, or BOR. We also found that the administration of L-OHP, PTX, VCR, and BOR elevated mRNA expression of Cav3.2, Cav3.3, and NR2A in the DRG of mice, whereas treatment with LEM abrogated L-OHP-, PTX-, VCR-, and BOR-induced Cav3.2 and NR2A mRNA expression. In addition, LEM treatment abrogated L-OHP-, PTX-, VCR-, and BOR-induced ERK1/2 phosphorylation in the DRG and spinal cord of mice. Furthermore, treatment with LEM reversed symptoms in mice that developed cold and mechanical allodynia after receiving L-OHP, PTX, VCR, or BOR.

Conclusion

These findings suggest that the attenuation of expression of phosphorylated ERK1/2, Cav3.2, and NR2A upon LEM treatment may be an effective prophylactic and therapeutic strategy against L-OHP-, PTX-, VCR-, and BOR-induced cold and mechanical allodynia.
Relationship between androgen deprivation therapy and kidney function in patients with prostate cancer: An analysis of the RADICAL-PC study.
Authors: Baskaran Geethan , Pinthus Jehonathan H. , Higano Celestia S. , Cano Garcia Cristina , Mian Rajibul , Dallegrave Cavalli Germano , Delouya Guila , Dusilek Cesar O.L. , Shayegan Bobby , Piccoli Rafaela Kirchner , Niazi Tamim , Davis Margot K. , Guha Avirup , Selvanayagam Joseph B. , Pardo Jose Enrique Cita , Luke Patrick P. , Leong Darryl
Published: February 2025

115

Background:
Androgen deprivation therapy (ADT) is an effective treatment for patients with advanced prostate cancer (PC). However, its impact on renal function remains underexplored. We evaluated the impact of ADT on kidney function in a cohort of patients with PC.
Methods:
We analyzed the RADICAL-PC study (Role of Androgen-Deprivation Therapy in Cardiovascular Disease—A Longitudinal Prostate Cancer study, NCT04127631), a prospective study of patients with PC in 10 countries. ADT use was assessed at baseline and follow-up visits. We quantified kidney function using glomerular filtration rate (GFR), calculated using the CKD-EPI equation and creatinine measurements obtained at annual visits. We used a linear mixed-effects regression model to analyze the association between ADT and change in GFR (ΔGFR), adjusting for age, diabetes, hypertension, renal disease, heart failure, chemotherapy, medications, alcohol use, and smoking. Using a Cox regression model, we assessed the association between ADT and acute kidney injury (AKI) as reported by sites.
Results:
Our analysis included 4119 participants with a median age of 68 (IQR 63-74) years. In 1791 (43%) participants using ADT at baseline, the ΔGFR over 2 years was -0.64 [95%CI -1.05 to -0.22] ml/min/1.73m
2
/year. In 2328 (57%) ADT-naïve participants at baseline, the ΔGFR was -1.00 [95%CI -1.34 to -0.64] ml/min/1.73m
2
/year. There was no significant difference in ΔGFR between the two groups (p=0.20). Age (β=-0.58, p<0.001), hypertension (β=-1.98, p<0.01), and anticoagulation use (β=-3.92, p<0.001) were associated with GFR decline. When analyzed as a time-varying covariate, ADT use was associated with less GFR decline than no ADT use (-0.21 vs. -1.07 ml/min/1.73m
2
/year, respectively, p<0.01). Duration of ADT use was not associated with ΔGFR (+0.04 [95%CI -0.02 to 0.10] ml/min/1.73m
2
/month, p=0.18). AKI developed in 91 (2.2%) participants over a median follow-up of 25 (IQR 12-36) months. Baseline ADT use was associated with an increased risk of AKI in univariate analysis (HR 2.58 [95%CI 1.67 to 3.98], p<0.001), but was not significant after adjustment for covariates (HR 1.37 [95%CI 0.83 to 2.26], p=0.22).
Conclusions:
This analysis suggests that ADT use is not associated with GFR decline or AKI incidence in patients with PC, challenging previous literature concerning ADT-related renal dysfunction. Further studies with longer follow-up periods are needed to confirm these findings.
Unraveling the dietary impact: Associations between ultra-processed foods and prostate cancer in a two-decade study.
Authors: Katsnelson Elise , Isrow Derek , Taswell Crystal , Rich Benjamin James , Jin William
Published: February 2025

135

Background:
Prostate cancer is a leading cause of cancer-related morbidity in men, and emerging research suggests that dietary patterns, particularly involving processed foods, may play a role in its development. This study aims to explore the association between NOVA-classified food consumption and prostate cancer.
Methods:
Data from the National Health and Nutrition Examination Survey (NHANES 1999-2018) was analyzed. A sensitivity analysis was performed. Men aged 20 and older with a diagnosis of prostate cancer (n=731) and without any cancer (n=20,972) were contrasted. The mean daily caloric intake from various NOVA food categories was analyzed using independent t-tests, then corrected using Benjamini-Hochberg (p<0.05). Subgroup analyses were conducted via Welch two-sample t-tests for age and BMI, while Chi-Square tests were used for race, education level, birth country, and military status.
Results:
Men with prostate cancer had a higher intake of the following NOVA group 4 ultra-processed foods: “cakes, cookies pies, pancakes” (p=0.031), “ice cream, ice pops, and frozen yogurts” (p<0.001), “sugared breakfast cereals” (p<0.001). They also had a higher intake of certain group 1 unprocessed or minimally processed foods: “roots and tubers” (p=0.019) and “fruits including juices” (p<0.001). Men without cancer had a higher intake of certain NOVA 1 unprocessed or minimally processed foods: meat/poultry (p<0.001), grains (p=0.002), pasta (p=0.025). They also ate more oils (NOVA 2 processed culinary ingredients, p=0.003), NOVA 3 processed foods like cheese (p<0.001), and many NOVA 4 foods like salty snacks (p=0.002), pizza (p<0.001), sandwiches/hamburgers (p=0.030), potato products (p<0.001), sauces/dressing/gravies (p=0.001), soft drinks (p<0.001), and sweetened beverages (p<0.001). Subgroups analyses revealed a greater association with prostate cancer for people with older age, Non-Hispanic Black and Non-Hispanic White races, being US-born, having a higher education, and serving in the military.
Conclusions:
To our knowledge, this is the largest study evaluating dietary behavior in the context of food processing and prostate cancer prevalence. We identified a high risk dietary pattern associated with industrially processed, calorically dense, and high glycemic index foods; conversely, a low risk dietary pattern was associated with minimally processed Mediterranean diets and, interestingly, highly processed Western diets.
Docetaxel rechallenge versus cabazitaxel in patients previously treated with docetaxel for metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Barata Pedro C. , Corrigan June , Culnan John , Dulberger Karlynn N , La Jennifer , Akama-Garren Elliot , DuMontier Clark , Hansen Jason Edward , Bitting Rhonda L. , Cheng Heather H. , Cooperberg Matthew R. , Dorff Tanya B. , Halabi Susan , Loeb Stacy , Nanus David M. , Pan Chong-xian , Schoen Martin W. , Fillmore Nathanael , Paller Channing Judith , Rettig Matthew ,   PROFOUND-VET Investigators Group
Published: February 2025

154

Background:
In 2004, docetaxel (DOC), a semi-synthetic taxane, received regulatory approval for mCRPC based on improved overall survival (OS). Cabazitaxel (CAB), a closely related analog of DOC, was approved in 2010 for mCRPC patients previously exposed to DOC. For patients previously treated with DOC, the relative benefits of docetaxel rechallenge (rDOC) versus a taxane switch to CAB are unknown. We aimed to evaluate the relative impact of rDOC versus CAB for patients who had previously received DOC for mCRPC.
Methods:
This retrospective cohort study compared outcomes of mCRPC patients in the nationwide VA healthcare system who received initial DOC, discontinued DOC for a reason other than disease progression, and later received rDOC or CAB after mCRPC diagnosis. Patients were eligible for inclusion if they received at least 3 cycles of DOC and at least 90 days later received a second course of DOC or CAB. The index date was the date of the start of the second course of taxane treatment. Time-to-event outcomes were evaluated from index date. Inverse probability of treatment weighting (IPTW) was used to control for potential confounders.
Results:
Between 1/2010 and 12/2023, a total of 669 patients (407 CAB, 262 rDOC) with median age 72, 29% Black, 27% CD, 39% CKD, 38% DM2, were included in final analysis. For the first instance of docetaxel, patients received a median of 6 (IQR: 4-10) cycles with a PSA50 = 20%, PSA90 = 3% and a median of 1 (IQR: 0-1) additional systemic treatment prior to subsequent taxane. At the time of the initiation of the second taxane, 73% of patients had bone and 18% visceral metastases and median initial PSA of 75 ng/mL. Compared to CAB, rDOC had higher PSA90 (11% vs 3%, p<0.001), longer OS (12.5 vs 9.6 months, p<0.001) and numerically longer time to next systemic treatment (16.4 vs 12.4 months, p=0.2), shorter time on treatment (2.1 vs. 2.6 months, p=0.56), and similar PSA50 (8% vs 9%, p=0.31). The use of platinum (9% vs 6%, p=0.15), immunotherapy (2 vs 1%, p=0.79) and PARP inhibitors (6% vs 5%, p=0.67) after the second instance of a taxane was not statistically different between groups.
Conclusions:
In this study, rDOC was associated with better survival and deeper response than cabazitaxel. The findings of this large-scale study provide guidance for making well-informed decisions about sequential use of taxanes for mCRPC treatment.
A phase II single arm prospective study of high dose testosterone in combination with carboplatin chemotherapy in late line metastatic castrate-resistant prostate cancer (HIGH-TeCH study).
Authors: Crumbaker Megan , Shekar Samantha , Lawrence Mitchell G. , Goldstein Leonard D , Yam Andrew O. , Downton Teesha , Begbie Stephen , Zielinski Rob , Fox William , Araiza Nicole , Yousif Jacob , Ratnayake Lalith , Antonarakis Emmanuel S. , Denmeade Samuel R. , Joshua Anthony M.
Published: February 2025

218

Background:
Bipolar androgen therapy (BAT) is a safe and well-tolerated treatment paradigm in metastatic castrate resistant prostate cancer (mCRPC) but response rates and duration are modest. Preclinical data suggests supraphysiologic androgens interrupt DNA relicensing and increase double-stranded DNA breaks, suggesting a potential synergy with the addition of carboplatin chemotherapy. We assessed the safety and efficacy of this treatment combination in Arm B of the HIGH-TeCH trial.
Methods:
Men with refractory mCRPC after at least one line of taxane based chemotherapy and androgen signaling inhibitor received four weekly testosterone enanthate (500mg IM) with Carboplatin (AUC 5) and androgen deprivation therapy. Five (24%) PSA50 responses were achieved at planned interim analysis of the first 21 patients, meeting threshold for study expansion to a total of 40 participants.
Results:
Currently, 37 of a target total 40 patients have been recruited. Median follow up was 14.8 months as of 1st October 2024. Median age 72. Median prior lines of treatment 3; 51% of patients had prior 177-Lutetium. 27 patients discontinued treatment for disease progression (PSA, radiological, clinical), 1 discontinued due to a serious adverse event (CVA) and 9 patients remain on trial. Median of 5 cycles of BAT with Carboplatin were administered. Seven (19%) patients had a PSA response ≥ 50%. Fourteen (38%) patients had clinical benefit (> 6 months duration on study). Median progression-free survival was 6.6 months (95% CI, 5.5 – 9.9). Median overall survival was 20.4 months (95% CI, 15.5 – not reached). Thirty-one (84%) patients experienced a treatment–related adverse event (TRAE); of which, 94% were grade 1 – 2. Highest rates of TRAEs were fatigue (52%), nausea (39%), musculoskeletal pain (23%), constipation (23%). There was no grade 4 TRAEs or deaths.
Conclusions:
BAT with carboplatin has an acceptable safety profile and demonstrated clinical benefit in heavily pre-treated mCRPC patients. Accrual will be completed imminently with final analysis to be presented. Translational studies to identify predictive biomarkers and quality of life analyses are underway. Clinical trial information:
NCT00309985
.
The prognostic impact of prostate-specific antigen at 6 months after post-prostatectomy radiotherapy: An individual patient data analysis of two NRG oncology randomized trials.
Authors: Mohamad Osama , Swanson David Michael , Pollack Alan , Lukka Himanshu , Dal Pra Alan , Dayes Ian S. , Martin Andre-Guy , Greenberg Michael , Balogh Alexander G. , Michalski Jeff M. , Vavassis Peter , Currey Adam D. , Dess Robert Timothy , Efstathiou Jason A. , Kapadia Nirav S. , Patel Samir , Ahmad Belal , Sandler Howard M. , Pugh Stephanie L. , Nguyen Paul L.
Published: February 2025

254

Background:
We sought to evaluate the prognostic impact of prostate-specific antigen (PSA) within 6 months of completion of salvage radiotherapy (RT) in patients treated with RT with or without hormone therapy (HT).
Methods:
Individual patient data were obtained from 2 randomized trials (NRG’s RTOG 0534 and RTOG 9601) evaluating salvage RT with or without HT. HT was either androgen deprivation therapy (ADT) for 4-6 months or bicalutamide for 2 years. The lowest PSA recorded within 6 months after RT completion was identified and categorized as ≤ or >0.1 ng/mL. The primary outcomes were metastasis-free survival (MFS) and overall survival (OS). Multivariable Cox proportional hazards regression was used to estimate hazard ratio (HR) with 95% confidence intervals to characterize the association of PSA within 6 months post-RT completion with OS and MFS while adjusting for age, Gleason score, trial, and HT use. Five-year MFS and 10-year OS rates were estimated using the Kaplan-Meier method.
Results:
Among a total of 2,373 patients, 1833 (77%) patients achieved a nadir PSA ≤0.1 and 540 (23%) did not. Among patients who did not get HT, 50% did not reach the milestone compared to only 6% of patients who got HT. PSA ≤0.1 ng/mL was associated with better OS (HR 0.27 [95% CI 0.12-0.6], p=0.001) and better MFS (HR 0.25 [95% CI 0.13-0.47], p<0.0001). The interaction test showed that the improved OS/MFS in patients who achieved the nadir was more prominent in those who did not receive HT compared to those who received HT. Five-year MFS rates among patients allocated to RT, RT+ADT, and RT+ bicalutamide were 94% vs 81%, 92% vs 87%, and 91% vs 93%, respectively, based on PSA ≤ vs >0.1. Ten-year OS rates among patients allocated to RT, RT+ADT, and RT+ bicalutamide were 87% vs 76%, 84% vs 84%, and 82% vs 83%, respectively, based on PSA ≤ vs >0.1.
Conclusions:
PSA >0.1 ng/mL within 6 months was prognostic for OS and MFS in patients treated with salvage RT in the post-prostatectomy setting. This finding allows better patient counseling and can guide clinical trial design for treatment intensification or de-intensification in patients receiving salvage RT.
Global spatiotemporal trends in prostate cancer burden and its socioeconomic disparities: An observational study from 1990 to 2021.
Authors: Zhou Xianghong , Wei Qiang
Published: February 2025

325

Background:
Prostate cancer is the second most common cancer in men globally, posing significant health challenges. Conflicting findings on its global burden and trends necessitate updated analyses. This study provides recent estimates of prostate cancer's global, regional, and national burden from 1990 to 2021, analyzes temporal trends, and offers epidemiological insights for clinicians, researchers, and policymakers.
Methods:
We analyzed data from the Global Burden of Disease Study 2021 on prostate cancer cases, deaths, and disability-adjusted life years (DALYs) from 1990 to 2021, including age-standardized rates (ASRs) for incidence, mortality, and DALYs. Trend analyses utilized average annual percent change (AAPC) calculations and joinpoint regression models. Age-period-cohort analysis assessed the effects of age, period, and cohort on incidence and mortality trends. Pearson correlation evaluated associations between ASRs and the Socio-demographic Index (SDI) to explore socioeconomic impacts.
Results:
From 1990 to 2021, global prostate cancer cases, deaths, and DALYs increased, reflecting aging populations. The age-standardized incidence rate (ASIR) showed a slight global increase (AAPC = 0.15, 95% CI: 0.05–0.25), while the age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) decreased (ASMR AAPC = -0.83, 95% CI: -0.92 to -0.74; ASDR AAPC = -0.75, 95% CI: -0.82 to -0.68), indicating improved survival. High-SDI regions had decreasing ASMR and ASDR despite high ASIRs due to better detection and treatment. Low-SDI regions saw increases in ASIR, ASMR, and ASDR, with the highest mortality and DALY rates, indicating rising burden and potential healthcare access issues. Joinpoint regression showed initial increases then decreases in ASIR, ASMR, and ASDR, with regional differences in timing. Age-period-cohort analysis revealed age effects with rising incidence and mortality risks, declining incidence risk in the oldest age groups. Period effects showed incidence risk increasing until 2011–2017, then declining; mortality risk decreased over time. Cohort effects showed stable then increasing incidence risk in younger cohorts, while mortality risk decreased across cohorts, reflecting healthcare improvements.
Conclusions:
The global absolute burden of prostate cancer has increased, but age-standardized mortality and DALY rates have decreased, especially in high-SDI regions due to advancements in detection and treatment. Low-SDI regions face rising incidence and mortality, highlighting growing disparities. Targeted interventions and resource allocation in low-SDI regions are needed to address the increasing burden and reduce global health inequalities.
AI-driven prediction of prostate cancer risk: A comparative analysis with C the Signs in the Mayo Clinic data platform.
Authors: Bakshi Bea , Raoof Sana , Haddad Tufia C. , Patel Tushar , Ryan Charles J. , Riaz Irbaz Bin , Dadhania Seema , Herrick Brian , Payling Miles
Published: February 2025

371

Background:
Prostate cancer is the most common malignancy in men globally and remains among the top five leading causes of cancer-related deaths. Emerging evidence suggests that early identification of symptoms can detect localized disease thus enabling opportunities for curative intent treatments. This study evaluates the use of the AI-powered prediction model, C the Signs, to passively screen for prostate cancer by leveraging data from electronic medical records (EMRs), offering a novel pathway for identifying high-risk individuals.
Methods:
A retrospective analysis was conducted using the Mayo Data Platform, encompassing 418,477 male patient records, of which 16,835 were diagnosed with prostate cancer. C the Signs identified patients at risk based solely on their EMR data, utilizing AI-driven pattern recognition. Sensitivity and specificity analyses were performed to assess the prediction model’s accuracy. Additionally, we examined the time-to-diagnosis advantage for patients flagged by the model compared to traditional physician clinical diagnoses.
Results:
C the Signs demonstrated a sensitivity of 83.3% and a specificity of 52.5% for identifying patients at risk of prostate cancer. Notably, 31.8% of prostate cancer cases were identified at risk up to five years earlier by the model compared to traditional physician clinical diagnosis.
Conclusions:
The integration of AI-driven prediction models like C the Signs into prostate cancer screening pathways provides an opportunity to enhance early detection, particularly in symptomatic individuals. Compared to prostate-specific antigen (PSA) testing, the model achieved equivalent sensitivity and 38% higher specificity, positioning it as a valuable companion tool for improving patient outcomes.
Efficacy and safety of lenvatinib plus everolimus in metastatic renal cell carcinoma after immune checkpoint and VEGFR tyrosine kinase inhibitors.
Authors: Lee So Heun , Park Inkeun , Yoon Shinkyo , Lee Jae Lyun
Published: February 2025

489

Background:
Limited studies have investigated the real-world effectiveness and safety of Lenvatinib (LEN) combined with everolimus (EVE) in metastatic renal cell carcinoma (mRCC), particularly after failure of immune checkpoint inhibitors (ICIs) and VEGFR tyrosine kinase inhibitors (TKIs). This study aimed to evaluate the efficacy and safety of LEN plus EVE in patients who had progressed after these prior therapies.
Methods:
This single-center retrospective study included mRCC patients at Asan Medical Center, Korea, who initiated LEN plus EVE as second-line or later therapy between September 2017 and June 2024. We reviewed electronic medical records for dosage, dose reductions, discontinuation, response, progression, and survival outcomes. The primary objectives were objective response rate (ORR) and progression-free survival (PFS), with secondary objectives including overall survival (OS), adverse events, and prognostic factors.
Results:
Eighty-two eligible patients were included, predominantly with clear cell type (n=74, 90.2%). ECOG performance status was 1 in 54 patients, and 2 in 26. At treatment initiation, the IMDC risk distribution was favorable (n=6, 7.3%), intermediate (n=48, 58.5%), and poor (n=28, 34.1%). The median number of prior therapies was four (range, 1-7), with 80.5% receiving LEN plus EVE as fourth-line or later therapy. All patients had prior anti-angiogenic TKI exposure, 86.6% had been treated with ICIs, and 37.8% had prior mTOR inhibitor therapy. The ORR was 39.0% (n=32/82), with a disease control rate (DCR) of 81.7% (n=67/82). The median follow-up duration was 21.8 months. The median time to progression (TTP) was 6.4 months (95% Confidence Interval [CI], 5.4-9.7), while the median PFS was 5.4 months (95% CI, 4.3-6.4), and the median OS was 7.7 months (95% CI, 6.2-12.1). Subgroup analyses indicated comparable ORR and PFS for patients treated beyond the fourth line (ORR 36.4%, PFS 5.3 months), those previously exposed to mTOR inhibitors (ORR 29.0%, PFS 5.5 months), and those who had progressed after both ICI and TKIs (ORR 38.0%, PFS 5.3 months). The median treatment duration was 6.8 months. Adverse events were significant: 54.9% required dose reductions of LEN, and 25.6% experienced treatment interruptions. For EVE, 17.1% required dose reductions, and 25.6% had interruptions due to toxicities. Notably, 31 patients (37.8%) developed proteinuria, with 18 experiencing grade 3 or higher.
Conclusions:
LEN plus EVE shows promising efficacy and disease control in heavily pretreated mRCC patients after failure of ICIs and VEGFR TKIs, even beyond the fourth line and in those previously treated with mTOR inhibitors. The safety profile aligns with known adverse effects, but the high incidence of proteinuria is notable. Further studies are warranted to optimize treatment protocols in this patient population.
Impact of belzutifan on anemia and hypoxia in sporadic and
VHL
-syndrome-associated renal cell carcinoma.
Authors: Siqueira do Amaral Paulo , Winer Aaron , Beckermann Katy , Chen Heidi , Lambrecht Morgan , Kaiser Elizabeth , Rini Brian I.
Published: February 2025

522

Background:
Inactivation of the tumor suppressor
von Hippel-Lindau
(
VHL
) gene is associated with
VHL
-syndrome-associated renal cell carcinoma (
VHL-
RCC) and sporadic renal cell carcinoma (spRCC). The inactivation of the
VHL
results in the accumulation of HIF-2a, promoting the expression of genes involved in angiogenesis and cycle-cell progression. Belzutifan, a HIF2α inhibitor, is approved for the treatment of
VHL
-RCC and spRCC patients (pts). Understanding the safety differences of belzutifan in these two populations can inform clinical management.
Methods:
This is a single-center, retrospective analysis of pts with spRCC and advanced
VHL-
RCC treated with belzutifan monotherapy between November 2018 and August 2024. The study population was separated into groups based on RCC type: spRCC
and VHL-
RCC. Demographic and clinical data were collected from medical records. The primary endpoints were the incidence of anemia and hypoxia. Continuous variables were reported as median with interquartile ranges (IQR) and compared using Wilcoxon rank-sum test. Categorical variables were presented as frequencies and percentage, with group comparisons performed using the Pearson Chi-Square test.
Results:
Pts with spRCC were older than those with
VHL
-RCC pts, with a median age of 67 y vs 41 y (p< 0.001), and were predominantly male, (68% vs 36%, p = 0.035). Reduced glomerular filtration rate (defined as < 50ml/min), was more prevalent in spRCC pts (36.5% vs 4.5%, p = 0.009). Baseline hemoglobin levels were similar between groups 13 g/dL (IQR: 10 – 14) vs.13 g/dL (IQR: 12.8 – 14.8).
VHL-
RCC pts received belzutifan for longer duration than spRCC pts (30.9 m vs 3.4 m, p < 0.001). In terms of safety, any-grade and Grade 3 anemia were similar between groups, 82% vs 91% (ns) and 54% vs 36% (ns), respectively. However, anemia developed more rapidly in spRCC pts, 29 d vs. 82 d (p <0.01) for any-grade, and 46 d vs. 104 d (p = 0.018) for grade 3 anemia. The need for blood transfusion was more frequent in spRCC patients (18% vs 0%, p < 0.05) as was the use of erythropoietin-stimulating agents 2% vs 4.5%, p = 0.08). Any-grade hypoxia was more frequent in spRCC pts (59% vs 18%, p 0.005), and there was a trend towards more grade 3 hypoxia (54.5% vs 9%, p = 0.052). Grade 3 hypoxia developed faster in spRCC pts (29 d vs 225 d, p = 0.039), the need for oxygen was more frequent in this population (52.5% vs 9.5%, p =0.003). Treatment discontinuations were more frequent in spRCC pts than in the
VHL
-RCC pts, 36.4% vs 4.5% (p = 0.009), 75% of discontinuations in spRCC were due to toxicity.
Conclusions:
Our cohort demonstrates differences in the safety profile of belzutifan between spRCC and
VHL
-RCC patients. These findings underscore the importance for personalized monitoring and management for each patient population.
Patterns of split-dose gemcitabine and cisplatin (GC) use in patients with locally advanced or metastatic urothelial carcinoma (la/mUC): Results of a 10-country physician survey.
Authors: O'Dwyer Richard Thomas , Junker Sophia , Szulkin Robert , Kienzle Scarlette , Kearney Mairead , Sridhar Srikala S.
Published: February 2025

699

Background:
Gemcitabine + cisplatin (GC) is a highly effective treatment for la/mUC. For patients who are ineligible for standard GC, split-dose GC is a promising alternative. This study aimed to provide insights into the use of split-dose GC and factors influencing treatment choice across 10 countries.
Methods:
Between January and March 2024, an international cross-sectional study was conducted via an online survey of physicians treating patients with la/mUC in Australia, Brazil, Canada, France, Germany, India, Italy, Spain, the UK, and the US. Demographics, practice patterns, and clinical parameters influencing treatment choice were collected. Multivariate logistic regression was used to determine factors influencing the use of split-dose GC.
Results:
The study included 791 physicians, mostly male (73%), who had a mean age of 43 years and an average of 13.2 years in practice, with 59% in academic practice. Most (85%) reported using split-dose GC across different treatment settings, including in 41% in neoadjuvant treatment, 40% in adjuvant treatment, and 43% in the metastatic setting. Physicians with the following characteristics were more likely to use split-dose GC: longer time in practice (per 10 years: odds ratio [95% CI], 1.58 [1.18-2.16]), higher patient volume (per 10 patients: 1.06 [1.01-1.14]), and public vs private practice (1.94 [1.27-2.97]). The preferred schedule in la/mUC was GC 35 mg/m
2
on days 1+8 of a 21-day cycle (57%). Most physicians (80%) used avelumab maintenance treatment after split-dose GC in patients without progression. The table shows acceptable lower thresholds for creatinine clearance (CrCl) reported by physicians for patients receiving split-dose GC.
Conclusions:
This large international survey underscores the extensive use of split-dose GC as an alternative regimen for patients with la/mUC who are ineligible for standard GC. Physicians who are more experienced and manage more patients are more likely to use split-dose GC. The results highlight the need for evaluating split-dose GC prospectively and establishing consensus guidelines for optimal use of split-dose GC in clinical practice and clinical trials.

Physiciansn=635

CrCl in patients with ECOG performance status 0-1, n (%)

50 mL/min
573 (90.2)

40 mL/min
407 (64.1)

30 mL/min
195 (30.7)

CrCl in patients with ECOG performance status 2, n (%)

50 mL/min
443 (69.8)

40 mL/min
290 (45.7)

30 mL/min
119 (18.7)