Browse Articles

Sex differences in the association between serum α-Klotho levels and hyperlipidemia: a cross-sectional study from NHANES 2013–2016

A phase 1/2 study of detalimogene voraplasmid (EG-70) intravesical monotherapy for patients with high-risk non-muscle invasive bladder cancer (NMIBC).

TPS886 Background: High-risk NMIBC is generally treated with adjuvant intravesical bacille Calmette-Guérin (BCG); however, ~50% of patients experience recurrence and/or progression after BCG and are considered unresponsive. Detalimogene voraplasmid (EG-70) is an investigational, intravesically administered therapy designed to elicit local stimulation of anti-tumor immune responses in the bladder and drive durable efficacy in BCG-unresponsive NMIBC, while mitigating the risk of systemic toxicities from immune stimulation. The Phase 1 (dose-escalation) portion of the first-in-human Phase 1/2, open-label, multicenter study (LEGEND; NCT04752722) of detalimogene voraplasmid is complete. The Phase 2 dose was identified, treatment was generally well tolerated, and the overall complete response (CR) rate was 73% [Kalota S, et al. AUA 2024]. Here we describe the ongoing Phase 2 portion of the study, which opened to enrollment in May 2023; a new cohort of papillary only (no carcinoma in situ [CIS]) disease is being included. Methods: Eligibility criteria: age ≥18 years; ECOG PS 0−2; NMIBC, with/without resected coexisting papillary tumors, ineligible for, or elected not to undergo, cystectomy; satisfactory bladder function. Patients receive detalimogene voraplasmid 0.8 mg/mL in 50 mL (intravesical administration, Weeks 1, 2, 5 & 6, 12-week cycle) for 4 cycles: BCG-unresponsive with CIS (Cohort 1); BCG-exposed or BCG-naïve with CIS (Cohort 2); BCG-unresponsive with high-grade papillary bladder cancer without CIS (Cohort 3). Phase 2 primary endpoints: efficacy (CR rate at Week 48); safety. Secondary endpoints: progression-free survival; CR rate at Weeks 12, 24, 36, and 48; duration of response. The study is being conducted in accordance with the ethical principles of the Declaration of Helsinki and is consistent with ICH/GCP. All patients provide written informed consent. The Phase 2 portion of the study is enrolling and will recruit up to 300 patients from sites in the USA, Canada, Europe, and the Asia-Pacific region. Clinical trial information: NCT04752722 .

A survival prediction model for veterans with advanced bladder cancer (BC) treated with immune checkpoint inhibitors (ICI).

855 Background: ICIs have been associated with improved survival for patients with BC and are now an integral part of the treatment paradigm. However, predictive biomarkers for ICI in BC have not been established. Here we report outcomes for veterans with BC treated with ICI and evaluate a prediction model based on clinical and genomic characteristics. Methods: We analyzed a cohort of 456 patients with BC treated with single agent anti-PD1/PDL1 therapies from 2019 to 2024 in the VA Informatics and Computing Infrastructure (VINCI) database, and also received FoundationOne CDx testing. Genomic analysis included gene mutations, copy number variants (CNV), and key biomarkers such as PDL1 CPS expression, and tumor mutational burden (TMB). PDL1 expression was stratified into high (>10) and low (<=10); TMB was stratified high (>=10) or low (<10). Genes and CNVs mutated in at least 5% of the population were used in univariate cox proportional hazards models predicting for overall survival (OS). Significant genes (p< 0.2) were then incorporated in a multivariate model adjusting for current biomarkers and demographic variables. OS analyses were conducted from the first immunotherapy to death or last follow-up date utilizing the cox proportions hazard model. Model performance before and after removing the significant genes was compared by concordance index with ANOVA. Results: In this cohort, the median follow-up time for patients alive was 17.5 months. The 2-year OS was 41.6% and the median time on treatment was 4.1 months. Gene mutations with a statistically significant association with OS in univariate analysis included: ERBB2 amplification, CDKN1A, CDKN2A.B loss, TP53, TERT promoter, ARID1A, FGFR3, CREBBP, and TRADD. In the multivariate analysis, low PDL1 expression (hazard ratio [HR] 1.82 95% confidence interval [CI] 1.26-2.64, p<0.005), TP53 mutation (HR 1.60, 95% CI 1.18-2.60, p<0.005), CDKN1A mutation (HR 1.66, 95% CI 1.06-2.61, p=0.02), and TERT mutation (HR 1.64, 95% CI 1.15-2.34, p=0.006) were significantly associated with decreased OS. Patients with FGFR3 wild type mutation were significantly associated with increased OS (HR 0.63, 95% CI 0.41-0.95 p=0.02). High TMB did not meet statistical significance for OS (HR 0.75, 95% CI 0.56-1.01, p=0.06). When all factors are included in the multivariable model the concordance index is 0.67. Conclusions: We report outcomes for veterans with BC treated with ICI. We highlight that PDL1 expression was associated with improved OS, while TMB did not meet statistical significance. We further highlight genomic variants that were associated with OS outcomes for patients with BC on ICI and propose a multivariable model. Current efforts are focused on training and validating machine learning algorithms to predict outcomes for patients with BC treated with ICI and ICI-combinations.

Association of androgen deprivation therapy and acute kidney injury in patients with prostate cancer: A systematic review and meta-analysis.

111 Background: Androgen deprivation therapy (ADT) has been associated with cardiovascular risk in prostate cancer patients. Thus, we performed a systematic review and meta-analysis to assess the incidence of acute kidney injury (AKI) in prostate cancer patients under ADT. Methods: PubMed, Embase, and Cochrane Library were searched from inception to October 2024. A random-effects model was employed to compute mean differences for continuous endpoints. Heterogeneity was evaluated by prediction interval and I-squared statistics. All statistical analysis was conducted using R software 4.4.1. GRADE approach rated the certainty of the evidence and the results were reported following the PRISMA statement guidelines. Results: Four studies involving 72,980 patients with a mean age of 73.5 years were included. Over a mean follow-up of 6.7 years, ADT was associated with an increase in the AKI incidence in prostate cancer patients compared to patients not receiving ADT (RR 1.34; 95% CI 1.13-1.58; p<0.001). Among patients who developed AKI while receiving ADT, the use of GnRH agonists was not associated with AKI incidence (RR 4.32; 95% CI 0.60-30.97; p=0.146). Similarly, when comparing AKI risk between patients on GnRH agonists alone and those without ADT, no statistically significant difference was found (RR 1.24; 95% CI 0.73-2.11; p=0.424). Orchiectomized patients had a lower AKI incidence than GnRH agonist users (RR 1.16; 95% CI 1.04-1.3; p=0.009). All studies were limited by retrospective designs, introducing potential selection and therapeutic bias. Conclusions: In this meta-analysis, ADT was associated with an increased risk of AKI. No statistical association was found between GnRH agonist use and AKI. Orchiectomy presented a lower AKI risk compared to GnRH agonists. Further investigations, including post hoc analysis of randomized controlled trials, are warranted to confirm these findings. Characteristics of the included studies. Study Sample size (n) Mean age (years) ADT modality Control group AKI incidence (ADT) AKI incidence (control) Hazard ratio for GnRH use (95% CI) – sensitivity analyses Follow-up (years) Gandaglia 2014 31,408 78.6 GnRH agonist and Bilateral orchiectomy No ADT 30.7% 24.9% 1.73 (1.62-1.85) 10 Cardwell 2021 10,751 69.2 GnRH agonists, GnRH antagonist, oral antiandrogens, estrogens and orchiectomy No ADT 6.1% 5.2% 1.09 (0.88-1.34) 3.9 Sherer 2021 27,868 66 GnRH agonists, oral antiandrogens, and GnRH antagonist No ADT +Radiotherapy 10.5% 7.9% 1.25 (1.13-1.37) a 8.8 Lapi 2013 2,953 80.2 GnRH agonists, oral antiandrogens, GnRH agonists + oral antiandrogens, bilateral orchiectomy, estrogens, other combinations No ADT 9.2% 4.5% ≈ 1.54 (1.17-2.15) b / ≈ 1.04 (1.27-1.46) c 4.1 a Sensitivity analysis of all ADT modalities. b Adjusted analysis of current ADT modalities. c Adjusted analysis of past ADT modalities.

Time perception in cerebellar and basal ganglia stroke patients

Prospective monitoring of prostate specific membrane antigen (PSMA) –positive recurrent prostate cancer: Preliminary data from 6 months PSMA follow-up.

45 Background: PSMA imaging can identify recurrent prostate cancer after definitive surgery/radiation prior to detection on computed tomography (CT) or bone scan. Radiation to PSMA+ findings is common but lacks clear data demonstrating long term benefit. PSMA+ recurrent prostate cancer (PSMArpc) is often defined and treated as metastatic castration sensitive prostate cancer (mCSPC), yet PSMA imaging alone as an eligibility criteria was never studied in the mCSPC trials. PSMArpc requires better understanding to define at-risk patients (pts). Methods: NCT05588128 enrolls pts after definitive and possibly salvage therapies. Pts are required to be 1 year removed from definitive therapy with a PSA≥0.5 ng/ml, testosterone≥100 ng/dL, and negative CT/bone scans. Lymph nodes (LNs) up to 1.5 cm and prior therapies are permitted. At enrollment pts have a baseline PSMA, which is repeated every 6 months (mos) if positive. If negative PSMA is done annually. CT and bone scans are also repeated annually. Pts are allowed to have radiation therapy or systemic therapies for ≤6 mos and remain on-study. Up to 350 pts will be enrolled and followed for up to 5 years. Results: Over 100 pts have enrolled since 3/2023 and 73 pts were evaluable after the 6-month PSMA scan/follow-up. The pts had a median age of 71 years, PSA=2.8, PSA doubling time=11.1 mos (30% less than 6 mos). In an overlapping descriptive analysis 10 pts were PSMA- and 15 pts had only local disease. For PSMA+ LNs, 15 pts had 1 LN, 8 pts had 2-3 LNs+, 4 pts had 4 LNs+, and 16 pts had 5+ LNs. 6 pts had bone findings, but negative bone scan. 3 pts had PSMA+ serosal nodules. After baseline PSMA 3 pts had radiation to solitary LNs, only 1 resolved/PSA declined. 1 pt elected androgen deprivation and 1 pt had salvage radiation. 4 pts enrolled in a clinical study at the NCI without androgen deprivation. At 6 mos PSMA scan only 2 pts had metastatic disease, both with bone scan findings, no pts had LNs beyond eligibility size criteria, and no pts had new visceral findings. Conclusions: These preliminary data from an ongoing study suggest PSMArpc is an indolent disease process and pts are at limited risk for clinically relevant progression within 6 mos. This study continues to accrue at the NCI and will seek to better define high-risk PSMArpc. These preliminary data may better inform the risks/benefits of aggressive treatment of PSMArpc and clinical studies in PSMArpc. Clinical trial information: NCT05588128 .

Circulating tumor cell expression analysis from the phase 2 trial of abiraterone, olaparib, or abiraterone + olaparib in first-line metastatic castration-resistant prostate cancer (mCRPC) with DNA repair defects (BRCAAway).

199 Background: Approximately 25% of patients (pts) with prostate cancer have deleterious germline/somatic homologous recombination repair mutations (HRRm). BRCAAway found the combination of an androgen receptor (AR) pathway inhibitor (ARPi) and poly(ADP-ribose) polymerase inhibitor (PARPi) as first-line therapy in pts with mCRPC and BRCA1/2 and/or ATM alterations to demonstrate longer progression-free survival (PFS) vs either agent alone or sequentially. Understanding AR signaling in HRRm (BRCA2 altered especially) versus intact patients and how they relate to response is unknown and may offer insights to mechanisms of resistance/sensitivity. Methods: Pts were randomized 1:1:1 to Arm1: abiraterone (1,000 mg)/prednisone (5 mg BID) (Abi), Arm2: olaparib (300 mg BID) (Ola), or Arm3: abiraterone/prednisone + olaparib (Abi + Ola). Internally analyzed, pooled circulating tumor cells (CTCs) were captured via bead-based EPCAM antibody with subsequent RT-PCR for gene expression profiling. Pretreatment samples from 47 pts across the three arms were compared to a historical CRPC cohort for difference and evaluated for a predictor of poor PSA response (stable PSA or progression by PCWG3). Results: A high probability of CTCs was found in 23 of 47 pts (48.9%, 11 Abi, 6 Ola, 6 Abi + Ola). In comparison to historical mCRPC pts, those with HRRm did not segregate from DNA repair intact pts regarding AR signaling. Also, PSA responders did not segregate from non-responders. Focusing on those with BRCA2 HRRm (20/23, 10 Abi, 5 Ola, 5 Abi+Ola), lack of PSA response was seen in 6/20 (30%). Combining the monotherapy cohorts, higher AR expression (median 22 for nonresponders and 15 for responders) correlated with lack of PSA response (unpaired t-test p=0.03), while ARV7 (median 18 vs 12) did not but may suffer from underpowering (p=0.20). Interestingly, the Abi+Ola cohort had a median AR expression closer to nonresponders (21.3), yet all 5 responded. Conclusions: Enriched CTC gene profiles from BRCAAway study pts prior to therapy in all arms appear similar to non HRRm mutant pts, supporting that the AR signaling pathway is consistently altered in mCRPC regardless of HRR status. For those with BRCA2 related HRRm, high AR expression associates with poor monotherapy response (Abi or Ola), but not the combination (Abi+Ola), suggesting the combination may rescue patients with AR addiction. Clinical trial information: NCT03012321 . BRCA2 cohort only (n=20) PSA ResponderMedian Gene Expression (IQR 25th/75th ) PSA NonResponder Median Gene Expression (IQR 25th/75th ) Unpaired t-test Monotherapy Cohort (Abi or Ola, n=15) AR 15.0 (13.7, 21.0) 22.0 (20.3, 23.2) P=0.03 ARV7 12.0 (3.8, 16) 18.0 (13.1, 19.7) P=0.20 Combination Cohort (Abi+Ola, n=5) AR 21.3 (20.3, 22.7) None N/A ARV7 16.3 (1.8, 18.0) None N/A

Association of PSMA PET results at biochemical recurrence (BCR) with metastasis free survival (MFS) by conventional imaging (CI) in patients with locally advanced or high-risk localized prostate cancer initially treated with radical prostatectomy (RP): A retrospective multicenter study.

355 Background: Prostate-specific membrane antigen (PSMA) positron emission tomography-computed (PET-CT) is used to stage prostate cancer (PCa) at BCR. PSMA PET-CT imaging has shown high sensitivity in detecting disease at slight prostate specific antigen (PSA) rise compared to CI. There remains an evidence gap in understanding the implications on treatment decision and clinical outcomes of PSMA-PET CT results at BCR after RP. We investigated the association of PSMA PET results with outcomes specific to MFS by CI in patients with BCR of locally advanced or high risk localized (LAHR) PCa treated with RP. Methods: We retrospectively screened from two academic centers patients with LAHR PCa who developed BCR after receiving RP as definitive therapy and underwent PSMA PET-CT imaging. We collected baseline characteristics including age at diagnosis, BMI, race and ethnicity, T-staging, Gleason score, and PSA. Interval treatment changes after and up to 60-days post BCR were captured. Outcomes were evaluated from 60-days post BCR. We estimated MFS by CI. A Time-to-Event (TTE) analysis was conducted between PSMA PET+ and PSMA PET- patients to estimate the effect of PSMA PET results on MFS by CI. PSMA PET+ status is defined as having evidence of a distant lesion by PSMA PET. 1:1 Propensity Score Matching (PSM) was applied to adjust for confounders using a 0.2 caliper between both groups. Results: We retrospectively identified a total of 333 LAHR RP patients with receipt of PSMA PET at BCR between January 2016 - January 2024. The median age at diagnosis was 63, with majority of patients being white (74.4%), while 4.1% were Black or African American and 6.2% were Hispanic or Latino. Patients had a median PSA at BCR of 1.1 ng/mL and 77.3% had a Gleason Score of 8 or higher. After adjusting for PSA at BCR and interval treatment changes, 111 PSMA PET+ and 111 PSMA PET- patients were included in the analysis. The overall median follow-up time was 47.3 (IQR: 21.2, 72.8) months. MFS was significantly shorter for PSMA PET+ versus PSMA PET- patients by CI (P-value: 0.006, HR: 2.39 CI: 1.3, 4.5) which remained after PSM (P-value: 0.012, HR: 3.0 CI: 1.2, 7.5). Conclusions: In this retrospective, multi-institutional study we investigated the association of oncologic outcomes in a LAHR PCa population receiving RP as definitive treatment and PSMA PET-CT at time of BCR. Our results show that MFS was 3 times shorter in patients with PSMA PET positive lesions at BCR. It is worth noting that a longer follow-up time may be needed to evaluate a robust association with overall survival. A plan is underway to replicate these analyses with a larger patient population at institutions in the US and Europe, aiming to confirm and extend the robustness of these estimates.

Effect of gold nanoparticles treatment on rats-induced obesity by evaluating body-composition directly and indirectly via bioelectric impedance analysis

Abstract Obesity is a metabolic disease characterized by an imbalance between caloric intake and expenditure, leading to excess fat and increasing the risk of various health conditions. This study compares the anti-obesity effects of gold nanoparticles (AuNPs) to orlistat in an experimental model of induced obesity in Wistar Albino rats. In addition to negative and positive control rats, obese rats were treated with variable daily and weekly doses of AuNPs and daily orlistat for nine weeks. Bioelectric impedance analysis (BIA) and dissection techniques were used to indirectly and directly measure body-composition in all rat groups. Hepatic and renal function and ultrastructure were assessed by blood biochemical and histological examinations to detect treatment-related alterations. High doses of AuNPs reduced body fat, increased muscle mass, improved dyslipidemia, glycemia, and antioxidant effects in obese rats, and restored normal TG, FBG, and MDA levels by reducing obesity-related oxidative damage. Histological and ultrastructural examinations showed that these high doses repaired liver and kidney cells, and reduced fat accumulation and body weight compared to the standard treatment for obesity by orlistat.

Implementation of a digital multimedia tool for prostate cancer patient consultation.

345 Background: MyCareGorithm, is a digital health tool designed to improve the cancer consultation experience for patients, companions, and physicians. This tool provides audiovisual guides for cancer related evaluation and management. This study aims to evaluate the effectiveness of this tool for both the patient and physician. Methods: In a prospective, IRB-approved, pilot study, 31 patients with prostate cancer and 12 companions from a single institution underwent an initial consult using this digital multimedia tool. They completed a survey of 6 “yes” or “no” questions to evaluate their understanding of their disease and treatment options. Two physicians completed a 7-question survey to evaluate their experience with this tool. Descriptive statistics were used to analyze the data. Results: Over 90% of patients reported this tool helped them better understand their cancer diagnosis, treatment options, and felt their understating of their medical situation and the quality of the consult was enhanced. 100% would recommend this to other patients. Their companions agreed and answered “yes” over 90% of the time in all categories. Comments from patients include phrase “very helpful” multiple times. Physicians agreed 97% of the time that this helped communicating difficult information and enhanced the quality of the consult. Physicians agreed that the patient had a greater understanding of their cancer, treatment, and that they would use this tool again 100% of the time. 94% of physicians agreed this tool improved efficiency and provided a more effective consult. Physician comments described the infographics as “helpful” in several instances. Survey questions and results are shown (Table). Conclusions: Implementing the MyCareGorithm digital health tool resulted in high levels patient satisfaction, comprehension, and enhanced the overall consult experience. Physicians also report high patient satisfaction and comprehension, enhancements to the overall consult, and improved clinical efficiency. The recurring comment from both physicians and patients was “helpful.” The positive results show the value of this digital communication tool. Further studies with a larger cohort and other disease sites should be assessed. Patient, companion, and physician survey questions and results. Survey Questions % Patients Agreed % Companions Agreed % Physicians Agreed Helped patient greater understand their prostate cancer 97% 100% 100% Helped patient greater understand treatment 90% 100% 100% Enhanced the quality of the consultation 97% 100% 97% Helped patient greater understand their medical situation 100% 100% - Would recommend this tool to other patients 100% 100% 100% Would review the information after consult 84% 92%* - Improved efficiency of the consultation - - 94% Helped physician provide more effective consult - - 94% Helped ease communication of complex information - - 97%

Impact of bleomycin shortage in patients with advanced testicular non-seminoma germ-cell tumors: A middle-income country cancer center experience.

623 Background: Standard of care for advanced NSGCTs is BEP (bleomycin, etoposide, cisplatin). Social, epidemiologic and economic factors can impact drug availability. In our institution, the COVID-19 pandemic limited accessibility to several antineoplastic drugs, including bleomycin. This analysis describes the frequency of BEP modifications and its impact in prognosis of intermediate (IP) and poor (PP) NSGCT treated at the National Cancer Institute in Mexico. Methods: Retrospective observational study performed from 2018 to 2022. Clinical characteristics and chemotherapy modifications were retrieved from electronic charts. Survival curves were built with Kaplan-Meier method and compared log-rank test to demonstrate effects of different clinicopathological variables on survival. Statistically significant variables in univariate analysis were included in multivariate Cox regression. Results: 179 patients included. Median age 23 (16-56). 33% had IP and 66% PP; 32% had non-pulmonary visceral metastases (NPVM). 60% had at least one dose modification. Median dose of bleomycin was 67.5 IU (IQR, IU 0-90) per cycle. 42% of patients received the full-dose of bleomycin (Bleo360) dose. 55.8% of bleomycin modifications were due to drug shortage. 88% who received Bleo360 didn´t have other chemotherapy drug modifications (p<.001). Median Progression Free Survival (mPFS) was 17.4 months (95% Confidence Interval (CI), 11.8-23.1). Median Overall Survival (mOS) was 73.6 months (95% CI, 20.6-126.7). Univariate and multivariate analysis are described in the table. Conclusions: Oncology drug shortages may have serious consequences for patient’s survival. In our cohort the dose-modifications of bleomycin had a deleterious impact in the survival of IP/PP NSGCTs patients. Policy modifications and stakeholders awareness is paramount to decrease shortage of “vintage” oncological therapies. Univariate and multivariate analysis. Univariate Multivariate Variable PFS HR(IC 95%) p OS HR(IC 95%) p PFS HR(IC 95%) p OS HR(IC 95%) p IPPP 0.34(0.21-0.56) <0.0001 0.3(0.2-0.5) 0.0001 Ref.2.4(1.4-4.2) 0.002 Ref.2.8(1.5-5.5) 0.002 NPVMNoYes 0.53(0.36-0.78) 0.001 0.5(0.4- 0.9) 0.011 Ref.1.3(0.9-2) 0.2 Ref.1.1(0.7-1.9) 0.6 Bleo360YesNo 0.6(0.66-0.98) 0.04 0.63(0.39-1.0) 0.06 Ref.1.3(0.9-2.0) 0.1 Ref.1.3(0.8-2.1) 0.3 Log Tumor MarkerFavorableUnfavorable 0.51(0.30-0.84) 0.009 Ref.2.1(1.2-3.7) 0.008 Ref.1.6(0.9-2.9) 0.1

Outcomes of enfortumab vedotin and pembrolizumab for patients previously treated with immune checkpoint inhibitors in the UNITE study.

867 Background: In trials testing enfortumab vedotin and pembrolizumab (EVP), prior treatment with immune checkpoint inhibitors (ICIs) was not permitted, resulting in a knowledge gap regarding efficacy of EVP in patients (pts) previously treated with ICIs. We hypothesized that EVP would have efficacy in pts with prior ICI exposure. Methods: In the retrospective UNITE study, we identified all pts treated with ICI prior to receiving EVP. The observed response rate (ORR) was assessed in evaluable pts who had imaging after ≥1 cycle of EVP. The following factors were evaluated to assess effect on EVP outcomes: type of ICI received (PD-1 vs PD-L1), prior pembrolizumab vs other ICI, time from last ICI to start of EVP, duration on prior ICI treatment, whether patient had clinical benefit (SD/PR/CR) to prior ICI, whether ICI was the immediate prior therapy line and whether it was the only prior line. ORR for these categories was compared using logistic regression, while progression-free survival (PFS) and overall survival (OS) from EVP start were analyzed using the log-rank test and Cox proportional hazards model. Results: Among 220 pts treated with EVP across 10 US sites, 43 (20%) had previously received ICI. Median age was 69 years; 34 (79%) were men, 40 (93%) were Caucasian, and 27 (63%) had pure urothelial carcinoma, 9 (21%) liver mets and 31 (72%) ECOG PS 0/1. Of 43 pts, 4 received ICI in the peri-operative setting (3 nivolumab, 1 pembrolizumab) and 39 in the metastatic setting (19 pembrolizumab, 8 avelumab maintenance, 6 nivolumab, 2 pembrolizumab maintenance and 1 each of atezolizumab, ipilimumab/nivolumab, durvalumab/tremelimumab, nivolumab/NKTR214). ORR was 48% (95% CI: 31 - 66) in 33 evaluable pts, with 13 (39%) PR and 3 (9%) CR; 30% had SD as best response (DCR 79%), and 21% PD. After median follow-up of 14 mos, median PFS was 6.9 mos (95% CI: 3.91 – 12.2) and median OS 15.4 mos (95% CI: 8.7 – NR). Outcomes by group are shown in the Table. Conclusions: Pts treated with EVP after prior ICI experienced high ORR and disease control rate. Results from this multi-site retrospective study are hypothesis-generating and require prospective validation in larger cohorts. Groups ORR PFS OS OR (95% CI) p-value HR (95% CI) p-value HR (95% CI) p-value Type of ICI (PD-1 vs PD-L1) 2.15 (0.36 – 17.49) 0.4 0.72 (0.32 – 1.61) 0.4 0.59 (0.23 -1.52) 0.3 Prior pembrolizumab vs not 0.54 (0.12 – 2.23) 0.4 0.55 (0.26 – 1.16) 0.1 0.40 (0.15 – 1.02) 0.05 Time from prior ICI* 1.01 (0.98 – 1.05) 0. 5 0.99 (0.98 – 1.01) 0.9 0.98 (0.96 – 1.02) 0.3 Time on prior ICI* 0.87 (0.74 - 0.98) 0.05 0.99 (0.94 – 1.05) 0.9 0.97 (0.89 – 1.05) 0.4 Clinical benefit to prior ICI (DCR vs PD) 0.50 (0.08 – 2.75) 0.4 0.70 (0.27 – 1.81) 0.5 0.89 (0.29 – 2.73) 0.8 Multiple prior lines vs ICI as only prior line 0.51 (0.11 – 2.29) 0.4 1.40 (0.57 – 3.44) 0.5 1.87 (0.54 – 6.43) 0.3 ICI as immediate prior line vs not 0.93 (0.15 -5.82) 0.9 0.56 (0.20 – 1.57) 0.3 0.53 (0.17 – 1.64) 0.3 *Continuous.

An integrated petrophysical and rock physics characterization of the Mangahewa Formation in the Pohokura field, Taranaki Basin

Abstract The Mangahewa Formation in the Pohokura gas field, Taranaki Basin, is a key reservoir for gas production in New Zealand, yet its deep and heterogeneous nature presents challenges for accurate reservoir characterization. While prior studies have explored aspects of the Mangahewa Formation such as lithology, fluid composition, and petrophysical properties, the interrelationships between these factors and their impact on hydrocarbon production remain underexamined. This study integrates detailed petrophysical and rock physics analyses to overcome these challenges. Petrophysical evaluation, based on well log data from depths of 3200–4000 m, reveals net reservoir thicknesses ranging from 164 to 479 m, with total porosity between 17 and 21% and effective porosity between 8 and 19%. Shale volume and water saturation vary from 21–28 and 22–34%, respectively. Rock physics analysis was performed using Rock Physics Templates (RPTs) to model the elastic properties of the reservoir. The Mangahewa Sandstone exhibits elastic properties consistent with the stiff sand model, with compressional sonic velocities ranging from 4100 to 5000 m/s. High correlations were achieved between measured and modeled velocities, with 97% for VP and 94% for VS. These models enabled the estimation of porosity from seismic-derived acoustic impedance, providing valuable insights in areas with limited well control. Furthermore, the RPTs effectively differentiated between gas sand, water sand, and shale facies, minimizing uncertainties in fluid and lithology prediction. These results provide a comprehensive understanding of the Mangahewa Formation, enhancing hydrocarbon prospect evaluation and supporting further exploration and development in the Pohokura field.

Evaluating the efficacy and safety of pelvic lymph node dissection in high-risk prostate cancer patients undergoing radical prostatectomy: A systematic review and meta-analysis.

390 Background: Pelvic lymph node dissection (PLND) is currently considered the gold standard for lymph node staging in prostate cancer patients. However, there is a paucity high-quality evidence demonstrating an oncological prognostic benefit of PLND in high-risk prostate cancer (PCa) populations, as defined by D'Amico risk classification. Methods: We conducted a comprehensive systematic literature review utilizing MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE databases. The search encompassed studies up to June 2024, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We identified original articles published in journals that reported survival analyses using Cox regression analysis and differences in hazard ratios (HRs) for the biochemical recurrence (BCR)-free survival (BRFS) (primary outcome) and metastasis-free survival (MFS), overall survival (OS) or cancer specific survival (CSS) (secondary outcomes). A meta-analysis of the effect of PLND on primary and secondary endpoints was performed using a random effects model. Results: Our analysis included seven studies, comprising one prospective and the rest retrospective. Pooled outcome data showed that PLND after radical prostatectomy did not independently predict BRFS (HR: 1.22; 95%CI: 0.99-1.50; p=0.006), MFS (HR: 1.21; 95%CI: 0.86-1.70; p=0.27), OS (HR: 0.91; 95%CI: 0.74-1.12; p=0.37), or CSS(HR: 1.02; 95%CI: 0.74-1.42; p=0.89) in high-risk prostate cancer patients. Heterogeneity was low to moderate. Conclusions: The available pooled analyses suggest that the therapeutic value of PLND is unclear. The high-risk PCa population should be carefully selected for lymph node dissection.

Multimodal management of oligometastatic and oligoprogressive renal cancer patients with extra-lung metastases: The KAIROS study.

507 Background: Patients with oligometastatic (OM-) or oligoprogressive renal cell carcinoma (OP-RCC) may benefit from metastasis-directed therapy (MDT) alone or in combination with systemic therapies. Literature data are available for IMDC favorable-risk patients with low-volume and asynchronous metastases, particularly to the lung. However, OM- and OP-RCC represent a heterogeneous population, and the current knowledge on the use of MDTs on extra-lung metastases remains limited. Methods: This was a real-world, multicenter, observational, retrospective study to assess the Time-to-Subsequent-Systemic-Treatment (TSST) in OM- and OP-RCC patient populations with at least 1 extra-lung metastasis undergoing MDTs [stereotactic body radiation therapy (SBRT), or surgical metastasectomy (SM)], during active surveillance (Cohort 1-OM), or upfront systemic treatments (ST) (Cohort 2-OP), as part of routine clinical care. Results: A total of 138 patients were included: 81 (58.7%) in the OM, and 57 (41.3%) in the OP cohort. Bone (44 lesions, 22.4 %), lymph nodes (33 lesions, 16.8 %), brain (28 lesions, 14.3 %), adrenal gland (26 lesions, 12.3%), soft tissues (14 lesions, 7.1%), liver (11 lesions, 5.6%), contralateral kidney (12 lesions, 6.1%), pancreas (10 lesions, 5.1%), peritoneum (7 lesions, 3.7%) or others (11 lesions, 5.6%) were the sites treated with MDT, for a total of 196 lesions: 139 metastases treated with SBRT (70.9%), and 57 (29.1%) treated with SM. In the Cohort 1-OM, a total of 112 lesions were treated with MDTs: 66 with SBRT (58.9%) and 46 with SM (41.1%). The median TSST was 43.0 months (95%CI 24.09-61.90); 73.2% and 60.5% of patients were free from systemic therapy at 1 and 2 years, respectively. In the Cohort 2-OP, 84 oligoprogressive lesions were treated: 73 with SBRT (86.9%) and 11 with SM (13.1%). Concomitant ST were: Tyrosine Kinase Inhibitors (TKIs) alone (25 pts, 43.9%), immune-oncology (IO) combination [IO-TKI (16 pts, 28.1%) or IO-IO (2 pts, 3.5%)], nivolumab (12 pts, 21.0%) or everolimus ± TKI (2 pts, 3.5%). The median TSST was 31.0 months (95%CI 24.32-37.68); freedom from subsequent systemic therapy at 1 and 2 years was 66.7% and 45.6%, respectively. Safety profile was favorable, with 1 Grade 3 and any Grade 4 SBRT-related toxicities or surgical complications reported. Conclusions: OM and OP-RCC do not have a clear standard of care, and data supporting the multimodal management of extra-lung metastases are lacking. Our real-world data suggest that the use of the SBRT and SM for the treatment of extra-lung metastases in patients undergoing AS or ST can be a useful strategy within a multidisciplinary approach, allowing the delay of systemic treatment initiation or escalation, with favorable toxicity rates.

Outcomes After Brexucabtagene Autoleucel Administered as a Standard Therapy for Adults With Relapsed/Refractory B-Cell ALL

PURPOSE On the basis of the results of the ZUMA-3 trial, brexucabtagene autoleucel (brexu-cel), a CD19-directed chimeric antigen receptor T-cell therapy, gained US Food and Drug Administration approval in October 2021 for adults with relapsed/refractory (R/R) B-cell ALL (B-ALL). We report outcomes of patients treated with brexu-cel as a standard therapy. METHODS We developed a collaboration across 31 US centers to study adults with B-ALL who received brexu-cel outside the context of a clinical trial. Data were collected retrospectively from October 2021 to October 2023. Toxicities were graded per American Society for Transplantation and Cellular Therapy guidelines for cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). RESULTS At the time of data lock, 204 patients had undergone apheresis and 189 were infused. Median follow-up time was 11.4 months. Forty-two percent of patients received brexu-cel in morphologic remission and would have been ineligible for participation in ZUMA-3. After brexu-cel, 151 achieved complete remission (CR), of which 79% were measurable residual disease (MRD) negative remissions. Median progression-free survival (PFS) was 9.5 months and median overall survival was not reached. Grade 3-4 CRS or ICANS occurred in 11% and 31%, respectively. In multivariable analysis, patients receiving consolidative hematopoietic cell transplantation (HCT; hazard ratio, 0.34 [95% CI, 0.14 to 0.85]) after brexu-cel had superior PFS compared with those who did not receive any consolidation or maintenance therapy. CONCLUSION Similar to ZUMA-3, high rates of MRD-negative CR were observed after brexu-cel treatment for R/R B-ALL. The use of HCT as consolidation after brexu-cel resulted in improved PFS.

Scheduling optimization based on particle swarm optimization algorithm in emergency management of long-distance natural gas pipelines

This paper aims to solve the scheduling optimization problem in the emergency management of long-distance natural gas pipelines, with the goal of minimizing the total scheduling time. To this end, the objective function of the minimum total scheduling time is established, and the relevant constraints are set. A scheduling optimization model based on the particle swarm optimization (PSO) algorithm is proposed. In view of the high-dimensional complexity and local optimal problems, the neighborhood adaptive constrained fractional particle swarm optimization (NACFPSO) algorithm is used to solve it. The experimental results show that compared with the traditional particle swarm optimization algorithm, NACFPSO performs well in both convergence speed and scheduling time, with an average convergence speed of 81.17 iterations and an average scheduling time of 200.00 minutes; while the average convergence speed of the particle swarm optimization algorithm is 82.17 iterations and an average scheduling time of 207.49 minutes. In addition, with the increase of pipeline complexity, NACFPSO can still maintain its advantages in convergence speed and scheduling time, especially in scheduling time, which further verifies the optimization effect of the algorithm in emergency management.

A frequency attention-embedded network for polyp segmentation

Population-based assessment of treatment patterns for high-risk localized prostate cancer.

349 Background: Patients diagnosed with high- or very high risk (H/vHR) prostate cancer (PCa) are at substantial risk of disease recurrence, metastasis, and death after treatment. Historically, treatment paradigms for these patients have been similar to those with intermediate-risk (IR) disease [radiotherapy (RT) with androgen deprivation therapy (ADT) and radical prostatectomy (RP)] though there is a growing body of evidence supporting intensified systemic therapy in this group. To contextualize this emerging trial data, we characterized real world treatment patterns for these patients. Methods: We performed a retrospective population-based cohort study using province-wide linked administrative data in Ontario, Canada. We descriptively characterized initial treatment patterns (within 1 year of diagnosis) for men with H/vHR PCa and compared them to a concurrent cohort of patients with IR disease to assess differences in management. Results: We identified 13,206 patients diagnosed with H/vHR PCa from 2010-2021 who were compared to 18,365 with IR disease. Most patients received active treatment, though rates were statistically significantly higher in the H/vHR (n=12,606, 95.5%) than IR cohort (n=14,995, 81.6%; p<0.001; standardized diff 0.44). 6207 (47%) of patients in the H/vHR cohort and 7286 (40%) of patients in the IR cohort underwent RP (p<0.001; standardized difference 0.148). Median time to RP was 98 days in the HR cohort and 105 days in the IR cohort (Median time (Q1-Q3); p<0.003; standardized difference 0.11). 6321 (47.9%) of those with H/vHR disease and 7427 (40.4%) of those with IR disease underwent radiotherapy (p<0.001; standardized difference 0.150). Very few patients received intensified systemic therapy: 77 patients (0.2%) received chemotherapy and 49 (0.2%) received androgen receptor pathway inhibitors. While treatment patterns were similar, patients with H/vHR disease were more likely to progress to metastasis (46% vs 30%, p<0.001) and more rapidly (2.6 vs 4.3 years, p<0.001), with similar patterns observed for CRPC, mCRPC treatment, prostate cancer events, and death. Conclusions: Despite higher rates of treatment, patients with H/vHR localized disease experience significantly worse clinical outcomes than those with IR. These data highlight the need for therapies which can improve clinical outcomes in this patient population, such as the potential use of intensified systemic therapies including Androgen Receptor Pathway Inhibitors (ARPIs).

Effectiveness and safety of RC48-ADC in combination with toripalimab as neoadjuvant treatment in HER2-positive muscular invasive urothelial bladder cancer patients.

710 Background: Bladder cancer with high expression of human epidermal growth factor receptor 2 (HER2) is associated with pathological malignancy and poor prognosis. For patients with muscle-invasive bladder cancer that can be curative resected, the standard treatment is radical cystectomy and pelvic lymph node dissection following neoadjuvant chemotherapy (NAC). However, NAC is inefficient, and many patients cannot tolerate its adverse reactions. Therefore, a novel and safe strategy for these patients is needed after NAC. Methods: In this study, patients with muscle-invasive bladder cancer (MIBC) diagnosed with cT2a-4aN0M0 who were HER2 positive (HER2 IHC1+, 2+, or 3+) and intolerant to platinum underwent transurethral resection of bladder tumor (TURBT). This was followed by 4 cycles of toripalimab (200 mg, intravenous, D1, Q2W) combined with disitamab vedotin (2 mg/kg, intravenous, D1, Q2W) as neoadjuvant therapy. For patients who requested bladder preservation, we performed Re-cTURBT or multipoint biopsy to verify the status of residual tumors in the bladder. The primary endpoint was pathological complete response (pCR). Secondary endpoints included objective response rate (ORR), overall survival (OS), and safety. Results: A total of 28 patients were enrolled from April 2023 to Jun 2024 in our hospital. The median age was 68 years (range: 55-82). By the data cut-off in June 2024, 16 patients (57.1%) achieved clinical complete response (cCR). Among those who achieved cCR, the primary endpoint of pCR was 93.7% (15/16). The median follow-up time was 11.8 months. The median OS was not reached, ORR was 96.4% (27/28). Regarding safety, treatment-related adverse events (TRAEs) of any grade occurred in 21 patients (75%). The most common TRAEs were fatigue (68.3%), itching (57.5%), poor appetite (51.2%), alopecia (33.3%), and diarrhea (16.7%), all of which are grade 1-2. Grade 3 TRAE occurred in 4 patients (14.3%), with one patient experiencing cardiac tachycardia (3.5%) and 3 patients having hepatic dysfunction (10.7%). No grade 4 and 5 TRAEs were observed. Conclusions: Disitamab vedotin (RC48-ADC) combined with toripalimab as neoadjuvant treatment has shown excellent effectiveness and safety in curative resectable MIBC patients with HER2 positive. Those who achieved cCR and underwent Re-cTURBT and multipoint biopsy in bladder had an excellent pCR.