Browse Articles

Ethnic disparities in clinical trials for FDA-approved drugs in prostate cancer: A post–COVID-19 era analysis (2020-2024).

25 Background: It is known that ethnic and racial inequality in participation in oncology clinical trial is a contemporary problem. Efforts have been made by NCI and FDA to address cancer disparities as per new policies placed in 2017. Despite these efforts, there are still disparities in cancer treatment and clinical trial participation. There is paucity of data in participation of minorities in the post COVID-19 era of the FDA approved agents in Prostate Cancer. Methods: From 2020-2024, a total of 4,744 patients participated in the seven clinical trials (MAGNITUDE, TALAPRO-2, VISION, PROPEL, ARASENS, HERO, PROfound and TRITON3) that led to FDA approval of new agents or indications to treat patients with prostate cancer. All clinical trials were industry-sponsored. We assessed and tabulated the reporting of racial demographics within these trials employing chi-square statistics and machine learning algorithms to compare participation rates among White, Black, Asian and Hispanic patients against SEER data on prostate cancer incidence. Results: Among the eight trials, five (ARASENS, MAGNITUDE, PROPEL, TALAPRO, TRITON-3) reported racial data in White, Asian and Black participants, but only one reported data on Hispanics (MAGNITUDE). Our analysis revealed that in the five trials providing racial data, 68% were White indicating statistically significant overrepresentation (p<0.001), Black participation was only 3% signifying statistically significant underrepresentation with (p<0.0001). In the only trial with data in Hispanics, there was a 12.1% participation of Hispanics with no significant disparity observed (p=1). Conclusions: Lack of representation of minorities persist in post COVID area FDA approved drugs clinical trials in prostate cancer. Lack of a more comprehensive data in race have also been seen in recent trials. Further implementation of policies for better data capture and standardization in the nomenclature of ethnicity should be pursued. Additionally, in international collaboration trials, a separate data on US participants utilizing NCI SEER data ethnicity nomenclature should be considered.

Development of an ex-vivo platform to model immunotherapy in kidney cancer.

592 Background: The treatment landscape for metastatic clear cell renal cell carcinoma (mccRCC) has evolved, with immune checkpoint inhibitor (ICIs) combinations contributing to improved survival. However, many patients remain unresponsive, highlighting the need for alternative strategies. While preclinical models have been instrumental in drug development, their translation to human applications often encounters challenges related to reproducibility. This emphasizes the urgent requirement for accurate, immunocompetent models of ccRCC that reflect human disease, identify effective immunotherapy regimens, and support reliable drug development. This study presents the development and characterization of a precision cut tissue slices (PCTS) model for primary ccRCC, capturing patient-specific heterogeneity. Methods: Twelve patients undergoing nephrectomy for primary ccRCC were consented. PCTS were obtained and co-cultured with autologous peripheral blood mononuclear cells (PBMCs) (5x10^5 co-cultured with one PCTS) and treated for six days. Treatment groups included: i) cabozantinib (cabo) alone, ii) cabo with cemiplimab (cemi, a PD-1 inhibitor), iii) cemi with fianlimab (fin, a LAG-3 inhibitor), and iv) the triplet regimen of cabo, cemi, and fin. The co-cultured PCTS were analyzed using H&E staining and a Live-Dead stain to assess cell viability. Following co-culture, PBMCs were imaged and cytospun for histological analysis and characterized using multiplex immunofluorescence (MxIF). Results: Viability assessment of co-cultured PCTS indicated a significantly higher proportion of dead cells in the triplet-treated group (cabo+cemi+fin) compared with either doublet strategy. Additionally, the number of viable PBMCs, assessed six days post-co-culture, was also highest in the triplet group. Ongoing MxIF analysis aims to characterize the PBMCs further. Conclusions: This study characterizes an organotypic, patient-derived model based on the culture of tumor slices from primary renal cancers, where we have optimized for extended viability of PCTS in ex vivo culture. The drug treatment experiments conducted on the slices demonstrate the potential of PCTS as a preclinical tool for screening effective therapies for primary ccRCC, including immunotherapeutic approaches, which has been challenging in previous animal models. Our findings suggest that the triplet regimen (cabo+cemi+fin) may offer greater efficacy compared to the cabo+cemi or cemi+fin. Based on these results, an early-phase clinical trial to investigate the triplet in ccRCC patients is under development.

High-performance GaSb-based interband cascade lasers with a top hybrid cladding

We report high-performance GaSb-based interband cascade lasers (ICLs) with a top hybrid cladding and operating around 3.5 μm at room temperature. Unlike the conventional superlattice (SL) claddings in GaSb-based ICLs, the top cladding of the present ICLs consisted of an n-SL, followed by an n+-InAs0.91Sb0.09 layer, while their bottom claddings entirely consisted of an n-SL. This “asymmetric” waveguide design is potentially advantageous, since it improves the active-core optical confinement factor, as well as the overall thermal conductance, especially for epitaxial-side-down mounted devices. When operated in pulsed mode, the broad-area ICL featured a characteristic temperature of 57 K and a threshold current density as low as 95 A/cm2 at 25 °C, which is the lowest ever reported for an ICL operating at a similar temperature. The narrow-ridge device processed from the same wafer, operated in continuous-wave (CW) mode up to a temperature as high as 100 °C, with a CW threshold current density of only 150 A/cm2 at 20 °C, although the current leakage was appreciable at the sidewalls.

Quantitative nylon monomerization by the combination of chemical pretreatment and enzymatic hydrolysis using nylon hydrolases

Nylons, derived from fossil fuels, are widely used for their toughness and flexibility, but they pose environmental concerns due to their low biodegradability. This study explored an efficient method for the monomerization of polymeric nylons, specifically nylon-6 and nylon-6,6, through a combination of chemical pretreatment and enzymatic hydrolysis using two kinds of nylon hydrolases, NylB and NylC (Nyl series enzymes). To break down the strong intermolecular hydrogen bonding between polymer chains of nylon, two pretreatment methods were investigated: homogeneous dispersion and soluble oligomerization induced by acid treatment. Homogeneous dispersion enhances water solubility, while soluble oligomerization reduces the molecular weight. These pretreatments significantly increased the enzyme sensitivity of the nylons, resulting in nearly complete conversion into monomers by Nyl series. Finally the convincing monomerization toward market products such as used fishing nets was also achieved. This study highlights the potential of this methodology for chemical recycling, offering a promising solution for reducing environmental impacts and achieving a circular economy for nylon products.

Association between breakfast nutrient density, subsequent meal quality, and overall diet quality in Iranian adults: a cross-sectional study

Lenvatinib's efficacy in heavily pre-treated metastatic renal cell carcinoma: Insights from a European multicenter study.

510 Background: Lenvatinib-based therapy has shown efficacy in the frontline treatment of metastatic renal cell carcinoma (mRCC). However, there is uncertainty about the role of Lenvatinib (LEN) in subsequent lines of treatment, particularly after immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI). This study aimed to describe the real-world clinical outcomes of patients (pts) with mRCC treated with LEN-based therapies beyond first-line treatment. Methods: Retrospective multicenter study including all pts with mRCC treated with LEN-based therapies beyond first-line at seven European centers from October 2020 to August 2024. Data on patient characteristics, treatments, and outcomes were collected. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS). Secondary endpoints included disease control rate (DCR), overall survival (OS), and safety. This study was approved by a centralized institutional review board (Gustave Roussy). Results: A total of 115 pts were included, 80% males, with a median age of 60.0 years. Of them, 80.9% had clear-cell subtype. Lenvatinib was mainly used after a median of 3 previous lines of treatment (range 2-8), either alone (41.7%) or in combination with everolimus (35.7%), pembrolizumab (PEM) (20.0%), or investigational agents (2.6%). Most of the pts had previously received ICI (88.7%) or TKI (96.5%), including cabozantinib (89.6%). The ORR was 28.2% and DCR was 65.5%. With a median follow-up time of 13.5 months (mo), the median PFS was 6.0 mo (95% CI 4.3-8.4 mo). Previous Cabozantinib (HR 4.3, p=0.02), bone metastases (HR 2.1, p=0.002) and the intermediate (HR 3.4, p=0.009) or poor IMDC risk (HR 7.7, p<0.001) significantly impacted PFS in the multivariate analysis. Median OS was 10.1 mo (95% CI 6.9-12.4 mo). Multivariate Cox models identified poor IMDC risk (HR 7.4, p<0.001) and bone metastases (HR 2.3, p=0.002) as negative independent prognostic factors for OS. On the contrary, LEN-PEM treatment (HR 0.3, p=0.017) had a positive impact on OS. Up to 38.3% of the pts started LEN with a dose adjustment (<18mg per day). On treatment, dose modifications were required in 33.9% of pts, with 9.6% discontinuing due to toxicities. Conclusions: In our cohort, LEN demonstrated meaningful clinical activity in heavily pretreated mRCC pts. The safety profile was manageable. These findings provide evidence to support its utilization in pretreated pts with mRCC.

Recurrence and its association with overall survival (OS) in muscle-invasive bladder cancer (MIBC) patients undergoing radical cystectomy (RC): A real-world analysis.

705 Background: MIBC is a heterogenous disease, encompassing T2-T4 tumors with or without nodal disease (T1-T4aN1). A primary treatment modality for MIBC is RC, often supplemented by neoadjuvant (NAD) and/or adjuvant (AD) therapies for select patients. Despite RC, patients with MIBC have a high risk of disease recurrence and progression. This study aimed to describe the real-world, contemporary impact of disease stage at diagnosis and treatment received on cancer recurrence and OS and examine the association between recurrence and OS. Methods: This retrospective study quantified recurrence and OS and the association of recurrence with OS among patients with MIBC (T2-T4aN0M0/T1-T4aN1M0) who had RC. Adult MIBC patients undergoing RC between January 1, 2008 and July 1, 2023 were identified using the U.S. ConcertAI Patient360 Bladder Cancer electronic medical record database in a predominantly community-based oncology setting. Index date was defined as the date of RC. Recurrence was defined as the first recorded disease progression >7 days after RC. Proportions of recurrence and OS were analyzed using Kaplan-Meier analysis overall and stratified by disease stage and treatment received. Association of recurrence with OS was assessed using Cox regression adjusted for patient characteristics. Results: 783 RC-treated MIBC patients met study inclusion criteria (median age 68 years; male 79%; White 88%; de novo MIBC 77%; urothelial histology 77%), with median follow up of 26 months (IQR: 11–48). At MIBC diagnosis, 73% were clinical stage T2N0, 21% were T3/4aN0, and 6% were T1-T4aN1. Almost half the patients (48%) underwent RC alone, while 46% received NAD+RC, 4% received RC+AD, and 3% received NAD+RC+AD. Over time, NAD use doubled from 30% (2011–2013) to 62% (2020–2022). Among patients who received NAD and had evaluable pathological staging (n=240), 26% achieved pathological complete response (pT0pN0). The overall 5-year recurrence rate was 45%, with variation by disease stage and treatment (Table). The 5-year OS was 48% overall and was significantly lower for patients with recurrence compared with those without (17% vs 69%, p<0.0001). Mortality was 4.4 times higher [95% CI: 3.5, 5.6] among those with recurrence compared to those without. Conclusions: MIBC patients undergoing RC had high recurrence rates, irrespective of disease stage at diagnosis or treatment modality received. Recurrence was associated with increased mortality rate. These findings underscore the substantial clinical burden for surgically treated MIBC patients and the need for more effective treatments that can delay or prevent recurrence and improve OS. Recurrence and OS by stage and treatment group. 5-Year Recurrence Rate % 5-Year OS Rate % Stage at MIBC Diagnosis T2N0 42 50 T3/T4aN0 52 47 T1-T4aN1 59 31 Treatment Group RC Alone 48 44 NAD+RC 39 56 RC+AD 67 29 NAD+RC+AD N/A 26

Cross resistance among novel androgen receptor axis-targeted agents in non-metastatic castration-resistant prostate cancer: A multi-institutional retrospective study.

395 Background: Previous studies reported a cross resistance among novel androgen receptor axis-targeted agents (ARATs) in patients with metastatic castration-resistant prostate cancer. However, the effects of sequential therapy with novel ARATs in non-metastatic castration-resistant prostate cancer (nmCRPC) remain unclear. Methods: This multi-institutional retrospective study included 56 patients with nmCRPC treated with second-novel ARATs after first-novel ARATs treatments, including apalutamide, enzalutamide, darolutamide, and abiraterone acetate between January 2014 and April 2024. The duration of novel ARATs treatment and PSA response were compared between first-use and second-use of novel ARATs. Results: The median age at nmCRPC diagnosis were 76 years. Of the 56 patients, 14 (25%), 16 (29%), 11 (20%), and 16 (29%) were treated with apalutamide, enzalutamide, darolutamide, and abiraterone acetate as second-novel ARATs. Median duration of novel ARATs treatment in second-use was significantly shorter than that in first-use (7.0 month vs. 14 month, respectively, P = 0.038). The rates of PSA decline ≥50% and ≥90% in second-use were significantly lower than those in first-use (25% vs. 73%, P < 0.001; 9.1% vs. 36%, P = 0.004; respectively). The rate of patients who did not achieve any PSA response in second-use was significantly higher than that in first-line use (45% vs. 11%, P < 0.001). Conclusions: A significant cross resistance among novel ARATs was observed in patients with nmCRPC. A further study is needed to evaluate the optimal candidates for sequential therapy with novel ARATs.

Association between sociodemographic marginalization and receipt of intensified treatment for metastatic castrate-sensitive prostate cancer.

96 Background: Intensified treatment beyond androgen deprivation therapy (ADT) has been shown to improve survival in patients with metastatic castrate-sensitive prostate cancer (mCSPC). However, real-world utilization remains inadequate. To assess potential differential access to such life-prolonging treatments, we assessed the association between sociodemographic marginalization and receipt of intensified treatment in patients newly diagnosed with mCSPC within a universal healthcare system. Methods: We performed a population-based cohort study of men aged 66 years or older diagnosed with de novo mCSPC in Ontario, Canada from Jan 2014-Nov 2021. Hierarchical regression models adjusting for patient, tumor, and physician characteristics were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between patient marginalization, measured by the Ontario Marginalization Index (ON-MARG), and receipt of intensified treatment, within 6 months of diagnosis. ON-MARG, a validated measure created using Canadian census data, provides area-level measures of marginalization in four domains: (1) households and dwellings; (2) material resources; (3) age and labour force; and (4) racialized and newcomer populations. Results: Among 6,051 patients, 1,465 (24%) received intensified treatment. Higher levels of composite marginalization were associated with a lower likelihood of receiving intensified treatment (OR 0.91, 95% CI 0.83–0.99, p=0.03). When examining individual domains of marginalization (Table 1), the racialized and newcomer populations domain showed the strongest negative association with the receipt of intensified treatment (OR 0.89, 95% CI 0.81–0.97, p=0.01). Conclusions: Sociodemographic marginalization, particularly among racialized and newcomer populations, is associated with lower rates of intensified treatment in patients with de novo mCSPC, even within a universal healthcare system, further contributing to known disparities in prostate cancer outcomes. Association between ON-MARG domains and treatment intensification among patients with de novo mCSPC in adjusted models.* ON-MARG Domain Effect Estimate (95% CI) Households & Dwellings OR 0.92 (0.85-0.98), p=0.02 Material Resources OR 0.93, (0.86-0.99), p=0.03 Age & Labour Force OR 0.99, (0.94-1.04), p=0.65 Racialized & Newcomer Populations OR 0.89, (0.81-0.97), p=0.01 *Each ON-MARG Domain was modelled in separate multivariable models adjusting for patient characteristics including age at diagnosis, Charlson comorbidity category, and area; tumor characteristics including Gleason score at diagnosis; as well as physician age, sex, years in practice, specialty, and group volume.

Design guidelines for Si metal–oxide–semiconductor and Si/SiGe heterostructure quantum dots for spin qubits

Si-based spin qubits are promising due to their long decoherence time and the compatibility with state-of-the-art semiconductor technology and have been demonstrated using quantum dots (QDs) to host single electrons for spin manipulation. In this work, we simulate the electrostatics and quantum transport properties of quantum dots on a Si metal–oxide–semiconductor platform and a Si/SiGe heterostructure. We investigate the effects of gate configurations and the SiGe spacer thickness on device characteristics, such as gate capacitances, Coulomb blockade, and charge stability. For a single quantum dot, placing its barrier gates (BGs) under the plunger gate improves the charge stability, while swapping the positions of those gates reduces the effects of the barrier gate biases on the charge stability. A thicker SiGe spacer further suppresses the effects of the barrier gate biases on the charge stability for quantum dots on the Si/SiGe heterostructure but leads to stronger crosstalk between neighboring quantum dots. Wider barrier gates can help to mitigate the crosstalk effects for multiple quantum dots. These findings provide key insights into the optimization of the gate configurations and material selection to improve the charge stability and minimize the crosstalk by different gates for future development of scalable Si-based quantum dots.

Author Correction: Follistatin like-1 aggravates silica-induced mouse lung injury

Trends in inpatient outcomes of bladder cancer: 2008-2021.

674 Background: Bladder cancer is a common malignancy of the urinary tract that is associated with about 16,840 estimated deaths in 2024. With the recent advances in bladder cancer treatment, it is unknown whether the trends in hospitalization outcomes have changed over time. We evaluated the trends in hospitalization outcomes among patients with a diagnosis of bladder cancer. Methods: This is a retrospective longitudinal trends study using the Nationwide Inpatient Sample (NIS) database (2008-2021). We identified hospitalizations with bladder cancer using ICD-9 and ICD-10 codes. Multivariate logistic and linear regression models were used to examine the trends in mortality outcomes stratified by demographic subgroups (age, gender and race). Results: There were over a million (1,123,567) hospitalizations with bladder cancer between 2008 and 2019. 73.5% were males; The mean age of the patients was 73.5 years. There was an overall increase in mortality amidst admissions with bladder cancer, from 4.5% in 2008 to 4.9% in 2021 (adjusted odds ratio [aOR]: 1.01; P-trend = 0.010). In the age subgroup, elderly patients (≥65 years) had an increase in mortality (aOR: 1.007; P-trend = 0.028). The young adults (18 - 44 years) and middle-aged adults (45 - 64 years) had no significant change in mortality rate (P-trend = 0.31 and P-trend = 0.131 respectively). For gender subgroup analysis, worse mortality outcomes were seen for males (aOR:1.01; P-trend=0.001); females had similar mortality over the period (P-trend=0.53). Racial subgroup analysis showed increased mortality outcomes for non-Hispanic White patients (aOR:1.01; P-trend=0.03). Black (P-trend=0.77) and Hispanic (P-trend=0.46) patients had no significant change in mortality outcomes. Conclusions: There was an overall increase in hospital mortality outcomes for bladder cancer patients from 2008-2021. While treatment advances continue to show improvement in survival outcomes, efforts are needed to ensure that hospitalized patients with bladder cancer have improved mortality outcomes. Inpatient mortality trends of bladder cancer stratified by demographic subgroups. Adjusted Odds Ratio P-Trend 95% Confidence Interval Overall Mortality 1.01 0.010 1.002-1.014 Young adults (18 - 44 years) 1.03 0.31 0.971-1.099 Middle-aged adults (45 - 64 years) 1.01 0.131 0.997-1.024 Elderly patients (≥65 years) 1.01 0.028 1.001-1.014 Male 1.01 0.001 1.005-1.019 Female 1.0 0.53 0.986-1.007 Non-Hispanic White 1.01 0.03 1.001-1.015 Black 1.00 0.77 0.979-1.016 Hispanic 0.99 0.46 0.968-1.015

Updated follow up of a randomized, double-blinded phase II study of ketoconazole (keto), hydrocortisone (HC), and anti-PSMA antibody J591 labeled with 177Lu or 111In in patients (pts) with high-risk non-metastatic (met) castration-resistant prostate cancer (M0 CRPC).

172 Background: Up to 1/3 of pts develop biochemical relapse following primary therapy. Many are not cured with salvage local therapy, likely because of undetectable distant disease. PSMA is expressed on most PC and can be targeted by radiolabeled J591. 177 Lu is a predominantly β-emitting radionuclide and also has γ emission which allows imaging. 111 In is predominantly a γ emitter, also with some auger emission for therapy. Hormonal therapy is effective and may increase PSMA expression and radiosensitivity. In this DOD-funded study initiated in the pre-PSMA PET and AR signaling inhibitor era, we hypothesized that 177 Lu prolongs 18-month (mo) met-free survival (MFS) more than 111 In in pts with high risk, M0 CRPC when targeting PSMA via J591 in combo with keto and HC. Methods: Pts with high risk M0 CRPC (PSA DT < 8 mo and/or absolute PSA > 20 ng/mL) and serum testosterone < 50 ng/mL with no evidence of metastatic disease on CT/MRI and bone scan were eligible. Treatment included a minimum 4 week lead-in with keto 400 mg TID and HC 20 mg AM, 10 mg PM (continued until unacceptable toxicity or development of mets) and a single infusion of J591 with 2:1 randomization to 177 Lu (70 mCi/m 2 ) or 111 In (5 mCi) in double-blinded fashion. 55 randomized pts provides 80% power to detect a difference in 18-mo MFS with one-sided alpha of 10%. Secondary endpoints include median MFS, overall survival, PSA response, and toxicity. Results: 55 pts with median age 68 (range 52 - 88), 75% prostatectomy, 23% primary radiation, 2% primary ADT; 19% local salvage therapy. Median PSA doubling time 3 mo (range 0.87 – 7.85), median baseline PSA 8.0 (range 1-78). In this intent to treat analysis (7 patients censored by 18 months), 31% of patients were without mets with 177 Lu compared to only 6.7% with 111 In (p=0.078) at 18 mo; biochemical PFS was 18.67 vs 8.87 mo, favoring 177 Lu in analyses censoring start of new treatment. Confirmed > 50% PSA decline occurred in 82% with 177 Lu and 71% with 111 In. The median MFS of the total patient population was 20.93 (CI: 17.02-34.2) mo, median 22.47 (CI: 17.35 to 68.11) mo for 177 Lu vs 20.5 (9.23-NA) mo for 111 In, p=0.65. The median overall survival of the total patient population was 76.35 (CI: 65.64-115.29) mo, no difference between 177 Lu and 111 In, p=0.48. With a median follow up of 63.8 mo, no new long term safety signals were discovered. Conclusions: PSMA-targeted 177 Lu combined with secondary hormonal therapy improves 18-mo MFS compared to PSMA-targeted 111 In. In the context of the current era with PSMA PET, this approach supports the early use of PSMA-targeted radionuclide therapy in patients with low volume mCRPC. Clinical trial information: NCT00859781 .

Phase II trial of image-guided oligometastatectomy and radiation therapy in recurrent prostate cancer (SOAR).

38 Background: In a subset of patients with molecular-imaging defined recurrent oligometastatic prostate cancer (PCa), salvage oligometastatectomy with surgery and/or radiation may provide improved androgen deprivation therapy (ADT)-free survival. Methods: This is a phase II trial with oligorecurrent PCa after primary prostatectomy or radiation therapy detected on Axumin (n=11) or Prostate-Specific Membrane Antigen (PSMA) (n=9) positron emission tomography. Oligometastatic disease was defined as ≤ 10 total sites, either of lymph node (LN) only (Group A), bone only (Group B), or LN and bone (Group C). Surgical intervention for patients with LN disease included extended pelvic and/or retroperitoneal LN dissection, depending on the location of the LNs. Groups A and C received adjuvant IMRT without ADT if PSA response was ≥ 1/3 decrease but remained ≥ 0.2 ng/dL. The primary outcome was a reduction in PSA by ≥ 50% at 6 months. Secondary objectives included PSA progression free-survival (PSA-PFS), ADT-free survival, and safety. Results: We accrued a total of 20 patients. The median age was 65 years (IQR 61-70), 95% (19/20) had an ECOG of 0, and 10% (2/20) were Hispanic. All patients had a prior prostatectomy, after which 45% (9/20) received adjuvant/salvage RT, with 33% (3/9) including the pelvis/ prostate bed. 30% (6/20) had exposure to ADT before trial treatment. The median time from definitive prostate cancer treatment to trial treatment was 2.8 years (IQR: 0.9-6.0). Oligorecurrent disease occurred as lymph nodes only (18/20; 90%) or bony (2/20; 10%). Within Group A, one patient completed adjuvant RT. The average number of imaging-identified positive LNs was 1.8 (range 1-6). The primary endpoint of reduction in PSA by ≥ 50% at 6 months was 40% (95%CI 19-64%) (Table 1). The secondary endpoint of PSA-PFS at 12 months was 84.4% (95%CI 66.6-100%). ADT-free survival at 12-months was 71.4% (95% CI 52.7% - 96.6%). There were no Clavien Grade III-IV complications. Conclusions: Salvage treatment of oligometastatic disease after prostatectomy or radiation identified on molecular imaging is feasible and safe. Nearly half the cohort had a good response to salvage treatment, demonstrated by a ≥ 50% reduction in PSA at 6 months. Ongoing analyses include comparing imaging and pathology correlations, and comparing complete/ partial responders and treatment failure. Further research is needed to identify ideal candidates for salvage treatment. Clinical trial information: NCT03796767 . PSA progression-free survival at 6- and 12-months (PFS). Time Estimate 95% Confidence Interval 6 months 100% --- 12 months 84.4% 66.6-100%

Safety and efficacy of bladder preservation therapy for very high-risk non-muscle-invasive bladder cancer: A single-center, single-arm prospective study (CIP-1).

805 Background: Radical cystectomy (RC) is the standard treatment for muscle-invasive bladder cancer (MIBC) and very high-risk non–muscle-invasive bladder cancer (NMIBC). However, many patients are unwilling or unable to undergo this surgery. Therefore, maximal tumor resection with concurrent chemoradiotherapy is an option. However, it has not been investigated adequately in NMIBC being received BCG which is prone to unresponsive until now. The study aims to evaluate the safety and efficacy of the comprehensive treatment for very high-risk NMIBC. Methods: The study prospectively selected the patients from January 2019 to July 2023. Inclusion criteria: 1) urothelial carcinoma pathology; 2) age <80 years; 3) tumor is possible to maximal resection; 4) muscle layer invasion-free and mpMRI VI-RADS score of 1-4; 5) no metastasis showed by CT or MRI. Exclusion criteria: 1) anterior urethra invasion; 2) dysfunction in bladder; 3) lymph node and/or distant metastasis; 4) persistent hydronephrosis; 5) absolute contraindications to chemoradiotherapy. After maximal tumor resection, patients with gemcitabine plus cisplatin (GC) neoadjuvant chemotherapy (NAC) as an optional treatment, were concurrent bladder radiotherapy (50-64Gy) and low-dose paclitaxel (50 mg/m2, D1/week) plus cisplatin (20 mg/m2, D1-2/week) chemotherapy. Record the adverse reactions, assess the recurrence and metastasis, and follow-up continued until October 2024 or death. Results: The study included 14 males (93.3%) and 1 female (6.7%); median age 60 (44–78) years, median follow-up 25 (11–75) months. 9 cases (60.0%) were initial presentation and 6 cases (40.0%, including 3 cases of BCG failure) were recurrence. 1 case had pathological subtype or CIS, respectively (6.7%). 7 cases (46.7%) approached GC NAC. The grade ≥III adverse reactions occurred in 10 instances: 6 episodes of leukopenia, 4 cases of radiation proctitis. 1 patient being incomplete the course (1/15) underwent salvage cystectomy (after 5 months). 2 deaths (2/14) occurred: 1 case developed posterior urethral metastasis after 19 months, refused further treatment, and died at 25 months; other case died at 20 months due to unexplained acute liver failure. 4 cases (4/14) experienced bladder recurrence at 10, 15, 20, and 28 months (T1 stage, single, <3cm, treated by TURBT), respectively. Among these 4 recurrence cases, only 1 (14.3%, 1/7) received NAC, while 3 (42.9%, 3/7) not. Patients completed the comprehensive treatment (14/15) had 1-year recurrence-free rate of 92.9% (13/14), tumor-specific mortality of 7.1% (1/14), median duration of response 23 (11–75) months, and post-recurrence bladder preservation survival 15 (5–39) months. Conclusions: The comprehensive treatment strategy for very high-risk NMIBC is safe and feasible, and NAC may improve the recurrence-free rate. Clinical trial information: 2000029504.

Distinct effects of Na and heavy alkali (K, Rb) incorporation in Cu(In, Ga)Se2 solar cells

Density functional theory calculations are performed to explore the nature of the alkali incorporation in Cu(In, Ga)Se2 (CIGS) thin-film solar cells. It is revealed that all the alkalis (Na, K, Rb) prefer to accumulate in the surface region of the absorber with occupying Cu sites. A hole barrier can be introduced in the absorber surface region, and the electron barrier at CdS/CuInSe2 interface is nearly changed after alkali incorporation. Distinct effects of Na and heavier alkalis (K and Rb) are explored. Post-deposition treatment (PDT) with Na leads to form NaxCu1−xInSe2 in the near-surface region. While monoclinic KInSe2 (or RbInSe2) secondary phase tends to form at the surface during K (or Rb) PDT. The hole barrier introduced by Na PDT can be much lower than that in the case of heavy alkali PDT due to the limited Na solubility in NaxCu1−xInSe2. The improved VOC in CIGS solar cells by heavy alkali PDT is mainly attributed to the absence of interfacial states and the elimination of isolated InCu and VCu defects in the surface region.

Concrete crack detection using ridgelet neural network optimized by advanced human evolutionary optimization

Real-world use and outcomes of darolutamide (DARO), enzalutamide (ENZA), and apalutamide (APA) for nonmetastatic castration-resistant prostate cancer (nmCRPC): Race subgroup analysis.

158 Background: Comparative real-world (RW) data on androgen receptor inhibitor (ARI; DARO, ENZA, APA) use in nmCRPC are limited. DEAR-EXT (NCT06013475) compared the RW utilization, tolerability, and outcomes of all 3 ARIs. Here we present a race subgroup analysis, based on data from the Black and White patient (pt) cohorts. Methods: DEAR-EXT is a retrospective chart review cohort study of men aged ≥18 years in the Precision Point Specialty Analytics network of US urology practices who initiated ARI treatment for nmCRPC for the first time (index date 8/2019–3/2023). Pts were categorized into White and Black cohorts based on their self-reported race. Key endpoints were time to and reasons for initial ARI treatment discontinuation, and metastasis-free survival (defined as time from index date until progression to mCRPC or death). Descriptive statistics and time-to-event analyses were conducted using unadjusted KM estimates and Cox proportional hazards models adjusted for baseline characteristics (age, race, insurance coverage, index year, PSA, time from nmCRPC diagnosis, and Gleason score). Results: A total of 282 Black and 923 White pts were included, of whom 41% received DARO, 44% ENZA, and 15% APA, in both race cohorts. Baseline characteristics were well balanced across treatment arms within each race cohort, except Gleason score and index year. Duration of follow-up was consistent across treatment subgroups (25.5–28.6 months). In both cohorts, the proportion of pts who discontinued their initial ARI treatment was lower for DARO vs ENZA or APA (Black: 33%, 45%, 49%; White: 38%, 53%, 50%, respectively). Similarly, in both race cohorts, progression to mCRPC or death was less frequent for DARO than ENZA or APA (Black: 26%, 35%, 42%; White: 34%, 49%, 45%, respectively). In adjusted Cox regression models, the risk of discontinuation and the risk of mCRPC progression or death in the DARO group were consistently lower in Black and White pts compared with ENZA and APA (range of hazard ratios [HRs] 0.49–0.79), while the differences between ENZA and APA were much less pronounced (HRs 0.80–1.16; Table). The most common reasons for ARI discontinuation were adverse events and disease progression/death, both occurring less frequently in the DARO group. Conclusions: DEAR-EXT real-world data reinforce DARO as an effective, well-tolerated treatment for nmCRPC, demonstrating potentially greater clinical benefits vs ENZA and APA among Black and White pts. Clinical trial information: NCT06013475 . Adjusted HR (95% Cl) DARO vs ENZA DARO vs APA ENZA vs APA Black pts Risk of ARI discontinuation 0.62 (0.40–0.97) 0.49 (0.28–0.88) 0.80 (0.47–1.37) Risk of mCRPC or death 0.79 (0.47–1.31) 0.67 (0.35–1.28) 0.85 (0.47–1.55) White pts Risk of ARI discontinuation 0.68 (0.54–0.85) 0.72 (0.53–0.96) 1.05 (0.80–1.38) Risk of mCRPC or death 0.60 (0.47–0.75) 0.69 (0.51–0.94) 1.16 (0.87–1.55)

Efficacy and toxicity profile of antibody-drug conjugate (ADC) based combination therapy in patients with advanced urothelial carcinoma (aUC): A systematic review of clinical trials.

813 Background: ADCs have revolutionized the treatment landscape of aUC and are being evaluated as part of combination regimens with checkpoint inhibitors (CPI) or other ADCs. We sought to evaluate the efficacy and safety/tolerability profile of ADC-based combination therapy in aUC. Methods: We systematically searched the PubMed and Embase databases for published prospective clinical trials through July 2024. Peer-reviewed clinical trials evaluating ADCs as part of a combination regimen in aUC were included. We extracted safety and efficacy outcomes, including objective-response rate (ORR), any-grade adverse events (AEs), and grade ≥3 AEs. We excluded reviews, editorials, retrospective studies, and case reports. Two independent reviewers screened titles and abstracts for relevance, followed by a full-text review to confirm eligibility. Results: 627 evaluable patients from 5 prospective trials investigating enfortumab vedotin or sacituzumab govitecan were identified. Overall, we recorded an ORR of 66.2%. 366 patients across all studies experienced ≥ grade 3 AEs, for a risk rate (RR) of 58.4%. By using a random-effects model, the pooled RR for AEs (Grade≥3) was 61% (95% CI, 52%–69%; P=0.18; Table). The most common grade ≥3 AEs were neutropenia (RR 0.14 [95% CI 0.04- 0.40]), anemia (RR 0.10 [95% CI 0.03-0.30]), and maculopapular rash (RR 0.10 [95% CI 0.04-0.23]). Distribution of specific AEs varied significantly based on regimen, with a higher incidence of ≥grade 3 anemia, neutropenia, and diarrhea in SG-based combinations (SG+ EV and SG+ CPI). Conclusions: While ADC-based combination regimens show promising responses, they also have high rates of AEs in patients with aUC. Further clinical trials evaluating these combination regimens are crucial to further optimize the role of ADCs in this disease setting. Safety/tolerability profile for any grade and grade ≥3 AEs. Toxicity Any Grade Grade≥3 Risk rate, 95% CI Risk rate, 95% CI Anemia 0.31 [0.09; 0.66] 0.10 [0.03; 0.30] Neutropenia 0.24 [0.05; 0.65] 0.14 [0.04; 0.40] Diarrhea 0.51 [0.19; 0.82] 0.07 [0.02; 0.17] Peripheral sensory neuropathy 0.50 [0.47; 0.54] 0.03 [0.02; 0.05] Fatigue 0.45 [0.26; 0.65] 0.06 [0.03; 0.13] Maculopapular rash 0.36 [0.26; 0.47] 0.10 [0.04; 0.23]

Sarcopenia as a marker to assess the surveillance necessity after a 5-year cancer-free period in patients who undergo radical cystectomy: A multi-institutional retrospective study.

871 Background: Although continuous surveillance after a 5-year cancer-free period in patients with bladder cancer (BC) who undergo radical cystectomy (RC) is recommended, optimal candidates for continuous surveillance remain unclear. Sarcopenia is associated with unfavorable prognosis in various malignancies. Thus, we hypothesized that sarcopenia, characterized by low muscle quantity, might be a useful marker to assess the necessity of surveillance after a 5-year cancer-free period in patients who underwent RC. Methods: This multi-institutional retrospective study included 274 patients with muscle-invasive bladder cancer (MIBC) who had a 5-year cancer-free period after RC. Muscle quantity was evaluated using the psoas muscle index (PMI) using computed tomography images five years after RC. The optimal cut-off values for all-cause mortality were calculated separately for men and women using receiver operating characteristic curves. Patients with lower PMI values than the cut-off values were diagnosed with sarcopenia. Recurrence-free survival (RFS) and overall survival (OS) after a 5-year cancer-free period were evaluated using the Kaplan–Meier method and compared using the log-rank test. Moreover, univariable and multivariable Cox proportional hazards regression analyses were performed to evaluate the impact of sarcopenia on OS. Results: The median age and follow-up period after the 5-year cancer-free period were 73 years and 63 months, respectively. Of the 274 patients, 129 (47%) were diagnosed with sarcopenia five years after RC. By the end of the follow-up period after the 5-year cancer-free period, 14 (5.1%) and 77 (28%) patients experienced recurrence and died from any cause, respectively. The 10-year RFS rate was 93%. RFS was not significantly different between the two groups, whereas OS in the sarcopenia group was significantly shorter than that in the non-sarcopenia group. After adjustment for confounding variables, sarcopenia was significantly associated with shorter OS (Table). Conclusions: Patients with sarcopenia might not need continuous surveillance after a 5-year cancer-free period, considering the high mortality rate. Multivariable analysis for OS. Factor P value Hazard ratio 95% CI Age Continuous <0.001 1.065 1.027–1.105 Performance status Continuous 0.012 1.829 1.145–2.922 Hypertension Positive 0.011 1.897 1.157–3.110 eGFR Continuous 0.168 0.990 0.976–1.004 Urinary diversion Neobladder 0.033 0.546 0.313–0.953 Sarcopenia Positive 0.025 1.801 1.076–3.012