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Association of baseline and on-treatment ctDNA fraction with clinical outcomes in patients with mCRPC in the PSMAfore study of ¹⁷⁷ Lu-PSMA-617.

16 Background: In PSMAfore (NCT04689828), [ 177 Lu]Lu-PSMA-617 ( 177 Lu-PSMA-617) prolonged rPFS versus androgen receptor pathway inhibitor (ARPI) change in taxane-naive adults with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) progressing once on an ARPI. Baseline circulating tumor DNA (ctDNA) fraction was associated with rPFS at the second interim analysis (IA) of OS (ASCO 24). Here, we assessed the association of baseline and cycle 2 day 1 (C2D1) ctDNA fraction, and early ctDNA and prostate-specific antigen (PSA) dynamics, with rPFS and OS at the third IA of OS. Methods: Patients were randomized 1:1 to 177 Lu-PSMA-617 (7.4 GBq Q6W; x6) or ARPI change. Endpoints included rPFS (primary) and OS (key secondary). Plasma ctDNA fraction was analyzed at baseline and at C2D1 using an in-house custom panel. Cox regression (adjusted for 3 risk classes based on clustering of 17 baseline clinical features) and random forest (adjusted for 15 baseline clinical features) modeling were used to assess the association of ctDNA fraction and PSA with clinical outcomes at the Feb-27-2024 data cutoff. Results: Patients with plasma samples at baseline and C2D1 were included ( 177 Lu-PSMA-617, n/N = 82/234; ARPI change, n/N = 91/234). Cox regression models adjusted for clinical features in the 177 Lu-PSMA-617 arm showed that higher ctDNA fraction was associated with shorter rPFS and OS (Table). These associations were stronger for C2D1 than baseline, both when comparing individual models and within a model including both timepoints (Table). In random forest models including clinical features and C2D1 ctDNA fraction, the total area under curves were not improved by addition of baseline ctDNA fraction (rPFS, 0.87; OS, 0.86). In the overall population, fractional decreases from baseline to C2D1 in ctDNA ( p = 0.0015) and PSA ( p < 0.0001) were strongly associated with longer rPFS, and were weakly correlated with one another (correlation coefficient, 0.26). In the 177 Lu-PSMA-617 arm, fractional decrease in ctDNA ( p = 0.002) was more strongly correlated with OS than was decrease in PSA ( p = 0.12). Conclusions: This exploratory analysis suggested that C2D1 ctDNA fraction was more strongly associated than baseline ctDNA fraction with rPFS and OS. Early ctDNA fraction dynamics contributed additional information in the prediction of rPFS and OS beyond PSA dynamics alone. Clinical trial information: NCT04689828 . Cox regression models. a rPFS OS Baseline model, HR (95% CI); p 6.0 (1.6–23.0); 0.0095 12.0 (3.0–48.7); 0.00052 C-index ± SE 0.69 ± 0.04 0.75 ± 0.04 C2D1 model, HR (95% CI); p 47.7 (10.1–226.0); < 0.0001 82.7 (16.4–417.0); < 0.0001 C-index ± SE 0.72 ± 0.03 0.77 ± 0.03 Baseline + C2D1 model Baseline, HR (95% CI); p 3.1 (0.7–14.0); 0.14 2.1 (0.4–12.7); 0.41 C2D1, HR (95% CI); p 35.9 (7.2–180.0); < 0.0001 52.5 (7.6–362.0); < 0.0001 C-index ± SE 0.72 ± 0.03 0.79 ± 0.03 a HRs correspond to 1 unit change in ctDNA fraction.

Topographically selective atomic layer deposition within trenches enabled by an amorphous carbon inhibition layer

To meet the demands for more advanced computer chips, creating devices with advanced 3D architectures is becoming commonplace in the semiconductor industry. To ensure alignment between the different layers, the bottom-up technique of area-selective deposition (ASD) is promising. However, ASD may not always be feasible depending on the various surface chemistries present during manufacturing of complex semiconductor devices. Topographically selective deposition (TSD) is emerging as an alternative, focusing on differences in surface orientation rather than chemical properties. This work demonstrates a TSD supercycle approach in which atomic layer deposition (ALD) is directed to proceed exclusively within a 3D trench structure, by covering the top of the trench with an amorphous carbon (aC) inhibition layer. The aC layer is applied selectively on the top surface of the trench by exploiting the ion-radical synergy required for its deposition. Since the aC layer lacks adsorption sites for ALD precursors, growth of the target material is inhibited on the top surface of the trench, whereas it occurs selectively within the trench. After several ALD cycles of selective deposition of the target material, the aC layer is removed and reapplied in a supercycle recipe until sufficient material has been deposited in the trench. The selective deposition of an aC inhibition layer on the top surface of the trench, as well as the selective deposition of 3.0 ± 0.1 nm of TiO2 in a trench is demonstrated on a 3D nanostructure.

Effect of dietary anthocyanins on the risk factors related to metabolic syndrome: A systematic review and meta-analysis

Objective This meta-analysis aims to systematically investigate whether dietary anthocyanin supplementation can reduce metabolic syndrome (MetS)-related risk factors: abdominal obesity, dyslipidemia (low high-density lipoprotein cholesterol (HDL-C) and hypertriglyceridemia), hypertension, and hyperglycemia by conducting a meta-analysis of randomized controlled trials (RCTs). Methods A systematic search of 5 electronic databases (PubMed, Web of Science, Scopus, Cochrane Library, and Embase) was conducted from inception until April 25, 2024. A total of 1213 studies were identified, of which randomized controlled trials involving subjects with MetS-related factors, comparing dietary anthocyanin supplementation with placebo, and reporting results on anthropometric, physiological, and metabolic markers relevant to this study were selected. Depending on the heterogeneity of the included studies, a fixed-effect model was applied for low heterogeneity (I2 < 50%), whereas a random-effects model was employed when substantial heterogeneity was present (I2 ≥ 50%). The weighted mean difference (WMD) and 95% confidence intervals (CI) were calculated. Results This meta-analysis included 29 randomized controlled trials with 2006 participants. The results showed that dietary anthocyanins significantly improved various lipid and glycemic markers: HDL-C: increased by 0.05 mmol/L (95% CI: 0.01 to 0.10, p = 0.026), LDL-C: decreased by 0.18 mmol/L (95% CI: -0.28 to -0.08, p = 0.000), Triglycerides (TGs): reduced by 0.11 mmol/L (95% CI: -0.20 to -0.02, p = 0.021), Total cholesterol (TC): lowered by 0.34 mmol/L (95% CI: -0.49 to -0.18, p = 0.000), Fasting blood glucose (FBG): reduced by 0.29 mmol/L (95% CI: -0.46 to -0.12, p = 0.001), Glycated hemoglobin (HbA1c): decreased by 0.43% (95% CI: -0.74 to -0.13, p = 0.005). Weight: (WMD: -0.12 kg, 95% CI: -0.45 to 0.21, p = 0.473), Body mass index (BMI): (WMD: -0.12 kg/m2, 95% CI: -0.26 to 0.03, p = 0.12), Overall WC: (WMD: 0.18 cm, 95% CI: -0.51 to 0.87, p = 0.613), Systolic blood pressure (SBP): (WMD: -0.12 mmHg, 95% CI: -1.06 to 0.82, p = 0.801), Diastolic blood pressure (DBP): (WMD: 0.61 mmHg, 95% CI: -0.03 to 1.25, p = 0.061), Insulin levels: (WMD: -0.02 mU/L, 95% CI: -0.44 to 0.40, p = 0.932), HOMA-IR: (WMD: -0.11, 95% CI: -0.51 to 0.28, p = 0.573). Additionally, a 100 mg/day dosage of anthocyanins significantly reduced: Waist circumference (WC): by 0.55 cm (95% CI: -1.09 to -0.01, p = 0.047). Subgroup analyses based on intervention duration, anthocyanin dosage, health status, formulation, dosage frequency, physical activity levels, and baseline levels of corresponding markers revealed varying significances, particularly in relation to blood pressure. Conclusion Dietary anthocyanins effectively improve low HDL cholesterol, hypertriglyceridemia, and hyperglycemia, making them a promising adjunct for managing MetS. However, it is important to note that dietary anthocyanin interventions may raise systolic blood pressure (SBP) and diastolic blood pressure (DBP) depending on intervention dose, duration, participant health status, and formulation. Clinicians should fully consider these effects when recommending anthocyanin supplementation. Further long-term, well-designed, large-scale clinical trials are needed to draw definitive conclusions.

One lung ventilation during thoracoscopic lobectomy alters lung microbiome miversity and composition

The role of salvage cystectomy after prior trimodality therapy.

781 Background: Trimodality therapy (TMT) with transurethral resection followed by radiation of the urinary bladder and chemotherapy is associated with similar long-term survival rates compared to radical cystectomy (RC) for well-selected patients. Nevertheless, salvage RC may become necessary in 10% of patients receiving TMT. We aimed to assess the perioperative and long-term outcomes of salvage RC after prior TMT through a large multinational cohort study. Methods: We included patients with pure urothelial cancer of the urinary bladder. Patients undergoing salvage RC after prior TMT due to recurrence in the urinary bladder from 11 high-volume centers were matched with a propensity score matching on a 1:1 ratio with patients without prior TMT undergoing primary RC. The two groups were adjusted for institution, age, histological status, ASA score, and surgical technique. Results: We included 108 patients (54 per group) with a median age of 74 years (IQR: 66-78). The two groups did not differ in terms of operative time (TMT: 250 versus non-TMT: 251 minutes, p = 0.9), intraoperative blood loss (TMT: 550ml versus non-TMT: 600ml, p = 0.2), and perioperative Clavien-Dindo complications (p = 0.9). At a follow-up of 16 months (IQR: 6-38), 45 (42%) deaths occurred. Prior TMT was associated with higher mortality rates in the survival analysis (log-rank test: p = 0.037). Accordingly, the progression rates were higher in patients with prior TMT (log-rank test: p = 0.047). Conclusions: Salvage RC after TMT is associated with similar perioperative outcomes compared to primary RC. Nevertheless, patients undergoing salvage RC after TMT may present worse progression rates and overall survival in the long term. Therefore, systemic therapies should be considered in patients with recurrence after TMT.

Post chemotherapy retroperitoneal lymph node dissection (PC-RPLND) for metastatic pure seminoma.

639 Background: Surgical resection of post-chemotherapy residual masses for metastatic seminoma is discussed controversially with regard to oncological and functional outcome. Furthermore, the role of FDG-PET/CT to detect vital seminoma is still unclear. It is the aim of this study is to report the outcomes of patients with pure seminoma who underwent PC-RPLND. Methods: In this retrospective international, multi-institutional study, pure seminoma patients whounderwent PC-RPLND for marker negative, FDG-PET/CT positive residual masses > 3cm or a marker negative retroperitoneal relapse following first line chemotherapy between 2000 and 2023 were included. Patients with residual masses with stable disease, negative FDG-PET/CT findings, inadequate systemic chemotherapy, insufficient clinical data, positive markers, or with residual or relapsing masses following salvage chemotherapy were excluded. Perioperative and long-term outcomes of the patients were reviewed. Results: A total of 142 patients with a median (IQR) age of 39 (31 – 68) years were included. All patients received first-line cisplatin-based chemotherapy. 93% of PC-RPLNDs were performed via an open transperitoneal approach, and 7% underwent robotic surgery. 86 (61%) and 56 (39%) patients underwent a unilateral and a full bilateral resection, respectively. A nerve sparing procedure was performed in 29 (20%). Adjunctive surgery was performed in 53 (37%) patients, the most common of which were ureteral resection/repair in 19 (13%) pts, and vascular resection/repair 18 (13%) pts followed by nephrectomy in 12 (8.4%). Median (IQR) blood loss and length of hospital stay were 550 (300 – 5800) mL and 4 (2 – 18) days, respectively. Clavien - Dindo complications ≥ 3a developed in 16 (11.3%). Final pathology revealed necrosis/fibrosis in 98 (64%) and seminoma in 44 (36%). FDG-PET/CT for residual masses > 3cm was performed in 56 patients with a positive predictive value of only 23%. On multivariate analysis (MVA) IGCCCG good risk (OR: 5.86, 95% CI 1.9-18.09, p<0.001), solitary metastases (OR 4.77, 95% CI 1.29-17.68, p=0.017) and RPLND for non-relapsing seminoma (OR 0.1, 95% CI 0.02-0,21, p< 0.001) were associated with necrosis. Adjunctive surgery (OR 4.56, 95% CI 0.39-53.5, p=0.04), and FDG-PET/CT SUV > liver (OR 31, 95% CI 2.54 – 45.6, p=0.004) and marker negative progression (OR 19, 95% CI 5.6 – 31.2, p<0.001) correlated with the presence of viable seminoma. With a median (IQR) follow-up of 65 (3 – 175) months, 20 (14%) patients relapsed (9/44 seminoma, 10/98 necrosis). 3 (3%) patients died of disease. Conclusions: One third of patients with progressive or > 3cm FDG-PET-CT positive residual retroperitoneal masses following first-line chemotherapy for metastatic seminoma may have viable tumor. 80% of patients with viable seminoma can be cured by surgery alone.In selected cases, PC-RPLND may be a valuable option if performed in high-volume centers with expertise in testicular cancer management.

Optimizing treatment approaches in nested bladder tumors: A multicenter retrospective study.

743 Background: Identifying optimal treatment strategies in nested bladder tumors is critical. This multicenter study aims at evaluating progression-free survival (PFS) end overall survival (OS) according to disease extent, presentation and treatment including Bacillus Calmette-Guérin (BCG), radical cystectomy (RC) and chemotherapy (CT). Methods: Data were collected from 61 patients with nested bladder tumors across 5 centers over a 10-year period (2013–2023). Patients were stratified according to 1) time of diagnosis of nested variant (disease onset Vs recurrence) 2) disease extent (NMIBC vs MIB, vs cN+ Vs M+) 3) treatment groups based on their initial treatment: ( BCG ± RC vs RC only Vs RC + CT). Kaplan-Meier analysis was used to assess median PFS (mPFS) and median OS (mOS), while p-values <0.05 was used to determine statistical significance across groups. Results: The median follow-up was 30.6 months (95% CI: 16.4–40.6). At diagnosis 15 (24.6%) were NMIBC, 26 (42.6%) MIBC, 15 (24.6%) N+ and 5 (8.2%) metastatic (M). Of the 15 NMIBC 80% received initial BCG. Pts with nested bladder tumors at onset had worse PFS and OS (mPFS of 99.6 months (95% CI: 55.2-NR) and mOS of 107.3 months (95% CI: 71.6-NR) than those with nested bladder tumor at recurrence mPFS of NR (95% CI: 42.1-NR) and mOS 138.4 (95% CI: 51.7-NR). None of these differences were statistically significant. Patients with M and N+ stages showed a trend towards a worse prognosis than those with NMIBC and MIBC, with no statistically difference in mPFS and mOS between MIBC and NMIBC stages. According to treatment, the best mPFS and mOS were recorded among patients receiving RC and CT [mPFS 99.6 months (95% CI: 55.2-NR) and mOS of 107.3 months (95% CI: 107.3-NR)]. Those receiving BCG followed by RC group had a mPFS of 84.2 months (95% CI: 68.1-NR) and mOS of 85.9 months (95% CI: 71.6-NR) while those undergoing RC alone apparently had the worse mPFS of 42.1 months (95% CI: 42.1-NR) and mOS of 51.7 months (95% CI: 14.7.1-NR). None of these differences were statistically significant. Conclusions: This study represents the largest case series of nested bladder tumors. It suggests limited benefit from BCG treatment. Most patients had advance disease, most of NMIBC finally need CT. Diagnosis at recurrence and combination of RC and CT tend to better survivals. Analyses that are more detailed are ongoing to evaluate clinical benefits according to the different clinical features.

Survey-based study of treatment sequencing after first-line (1L) enfortumab vedotin/pembrolizumab (EVP) in the evolving landscape of locally advanced/metastatic (la/m) urothelial cancer (UC).

770 Background: EVP is a preferred 1st-line option for patients (pts) with la/m UC. We sought to understand how genitourinary (GU) medical oncologists in the US treat pts who progress on 1L EVP, and their comfort level with immune checkpoint inhibitor (ICI) rechallenge after prior ICI exposure. Methods: We convened a bladder cancer working group comprised of 11 expert la/m UC GU oncologists. This group created an 11-question survey addressing key questions regarding treatment sequencing, including treatment after 1L EVP. The survey was e-mailed to 227 US GU oncologists from May - Aug 2024. GU oncologists in the Bladder Cancer Advocacy Network and those with a known GU-focus in academic and community practices were selected. Here, we present results regarding 2L treatment after 1L EVP, using descriptive statistics. Results: We received 78/227 responses (34%); 72% report seeing > 25 pts with la/m UC/yr, 21% see 11-25 pts/yr. 71 oncologists completed the 2L treatment question. After progression on EVP, 77% (55/71) were somewhat/very likely to give platinum-based chemotherapy (PBC), 80% (57/71) would not include nivolumab with gemcitabine + cisplatin in the 2L, and 62% (44/71) were somewhat/very unlikely to give switch maintenance ICI after 2L PBC (Table). For other 2L options, 87% (62/71) were somewhat/very likely to give erdafitinib in pts with FGFR3 alterations (alt), and 56% (40/71) were somewhat/very likely to give sacituzumab govitecan (SG). SG use before and after TROPiCS-04 trial press release on 5/30/24 shifted from 63% (24/38) to 48% (16/33) somewhat/very likely to use SG (and 21% [8/38] to 39% [13/33] somewhat/very unlikely to use). Regarding clinical trials after 1L EVP, 80% (57/71) were somewhat/very likely to recommend a non -ICI containing trial. Conclusions: After progression on EVP, most GU oncologists favor PBC without combination ICI, PBC without ICI switch maintenance, or erdafitinib (in FGFR3-alt) as 2L therapies. For clinical trials 2L, more oncologists favor a non -ICI containing regimen. Additional data, including the impact of residual toxicity from 1L EVP on 2L treatment selection, and treatment of pts with HER-2 IHC3+ tumors, are needed to better understand treatment sequencing for pts with la/m UC. At the time of survey build, trastuzumab deruxtecan had recently received pan-tumor approval. Limitations include selection bias and lack of clinical outcomes. 2L Treatment after EVP Somewhat or very likely to use, % (n) Somewhat or very unlikely to use, % (n) Gemcitabine + Cisplatin + Nivolumab 11 (8) 80 (57) PBC with switch maintenance ICI 31 (22) 62 (44) PBC without switch maintenance ICI 77 (55) 13 (9) Erdafitinib for FGFR3 -alt 87 (62) 7 (5) SG 56 (40) 30 (21) ICI-combo trial 54 (38) 35 (25) Non-ICI trial 80 (57) 8 (6) Continue EVP for progression in 1-2 sites after using local therapy (e.g. radiation) 83 (59) 8 (6)

Anisotropic phonon responses of 2D NbOX2 (X<b>=</b>Cl, Br, I) under uniaxial tensile strain

The van der Waals crystal NbOX2 (X = Cl, Br, I) has recently attracted much attention due to its remarkable in-plane anisotropy and substantial second-order nonlinear optical response. Moreover, the importance of modulating its physical properties through strain has become increasingly prominent. Herein, we investigate the anisotropic phonon response of NbOX2 along various crystallographic directions under uniaxial tensile strain by Raman spectroscopy. The results show that opposing frequency shifts manifest in the Raman modes when uniaxial tensile strain is applied either parallel or perpendicular to the polar axis, and the highest frequency peak, P5, shows significant blue or red shifts. Density functional theory calculation results are consistent with the observed Raman shifts under strain. The change in Nb–O bond length is the main reason for the significant blue shift of P5. The anisotropic and pronounced frequency shifts of NbOX2 under strain can serve as sensitive indicators for strain modulation, offering insights for potential applications such as flexible optoelectronic devices and strain sensors.

User experience with pregnancy tracker mobile apps: Findings from comment-based qualitative study

Background Worldwide, millions of pregnant women use pregnancy-related apps to monitor their baby’s growth and development. While most of the apps are user-friendly, not all of them are equally appealing. This study aimed to explore the user experience (UX) of pregnancy tracker mobile apps used by pregnant women. Methods This study explored the dynamics between users’ experiences and multifaceted dimensions of advanced features, high-quality materials and information, strict privacy policies, problem-solving abilities, and the usefulness of app features and contents. This study applied reviewers’ comment-based qualitative study, accessing crowdsourced data gathered from different pregnancy tracker app websites. A thematic and content analysis approach was used. Results This study found that when users are satisfied with using advanced content and features, it aligns with their perceived self-righteousness and rationality, and reflects their cultural values and expectations of using the apps. Conversely, when users encounter challenges such as erroneous baby size comparison and app updating issues, they perceive these as disadvantages of the apps utilised. Moreover, the study sheds light on the specific desires of pregnant women, highlighting their expectations for content that addresses their physical and mental well-being, as well as their unborn babies. The desire for free access reflects the cultural emphasis on cost-effectiveness, while the willingness to invest financially in enhanced experiences demonstrates the recognition of the value and potential benefits of improved content and features. This study also provides valuable insights into the complex relationship between users’ experiences, cultural values, advanced features, high-quality materials and information, privacy policies, problem-solving abilities, and relevant content in creating positive app experiences that align with users’ cultural expectations and needs. Conclusion This study provides essential insights into the user experience and underscores the importance of a user-centric design approach for developers. By capturing the current landscape of these digital tools, can provide valuable feedback for the enhancement of existing applications and guide the development of future iterations, ensuring the diverse preferences and expectations of pregnant women worldwide.

Study on molecular mechanism of polyoxyethylene to prevent coal and rock and gas composite dynamic disasters

Decipher score as a predictor of response to treatment intensification in the NRG Oncology-RTOG 0534 (SPPORT) phase III randomized post-prostatectomy salvage radiotherapy trial.

399 Background: The three-arm randomized SPPORT trial (n=1792) examined the effect of treatment intensification on the outcome of men treated with salvage radiotherapy (RT) for a detectable PSA. The arms were prostate bed RT (PBRT) alone (Arm I), PBRT + short term androgen deprivation therapy (STADT; Arm 2), and PBRT + STADT + pelvic lymph node RT (PLNRT; Arm 3). With treatment intensification in Arms 2 and 3, there were significant incremental gains in the primary freedom from progression (FFP) endpoint, but not metastasis free survival (MFS) with about 8 yr median follow-up; although metastatic events were reduced with intensification. Decipher score (DS) is strongly prognostic for metastasis and was hypothesized to be independently significant of clinical-pathologic covariates in predicting the need for treatment intensification. The main objective was to determine if gene expression estimates of metastatic risk using Decipher score result in significant interactions with treatment, especially for PLNRT. Methods: Prospectively collected prostatectomy tissuewas available for RNA extraction and generation of DS (Veracyte, San Diego, CA) in 916 patients. The protocol FFP endpoint included biochemical (nadir+2 ng/mL) failure, clinical failure, or death from any cause. MFS included distant metastasis or death from any cause. Multivariable (MVA) Cox models adjusted for Gleason score, margin status, pT-stage, pre-RT PSA, age, and race. Results: DS (median 0.61; IQR: 0.45-0.79) were obtained for 709 patients (median follow-up 7.9 yr), with 215 in Arm 1, 247 in Arm 2, and 247 in Arm 3. The arms were balanced for key covariates. There were 226 FFP and 136 MFS events. On MVA, DS (per 0.1 unit) was prognostic for FFP (HR 1.10, 95% CI 1.03-1.17, p=0.007) and borderline for MFS (HR 1.08, 95% CI 0.99 - 1.18, p=0.08). There was no significant DS-related benefit to adding STADT to PBRT. Adding PLNRT + STADT to PBRT resulted in a greater benefit in patients with high (&gt;0.60, HR 0.36, 95% CI 0.25-0.54, p&lt;0.001) vs. lower (≤0.60, HR 0.76, 95% CI 0.46-1.26, p=0.29) DSs, with an absolute benefit of 27% vs. 11% in high vs. lower DS, along with a significant treatment interaction on MVA (p-int = 0.04). Relative MFS benefit from adding PLNRT + STADT to PBRT ± STADT was greater in patients with high (HR 0.60, 95% CI 0.37-0.97, p=0.04) vs. lower (HR 1.14, 95% CI 0.66-1.98, p=0.63) DS, with a 10-year absolute benefit of 6% vs. 0%, and a borderline significant treatment interaction on MVA (p-int = 0.06). Conclusions: The unique SPPORT trial intensification design facilitated the discovery that high metastatic risk, as assessed by DS, may be abrogated at least in part by PLNRT, suggesting that lymph node micrometastases are a sole site of metastasis in some patients. Decipher score is a meaningful predictor of gains from PLNRT. Clinical trial information: NCT00567580 .

Understanding incidence and outcomes of testicular and ovarian germ cell tumors from 2000–2017 using population-based cancer registries.

649 Background: Both testicular (TGCT) and ovarian germ cell tumors (OGCT) originate from a common primordial germ cell lineage prior to differentiation into sperm or eggs and share several features. While TGCT are extensively studied, less is known about OGCT but given the relative rarity of both TGCT and OGCT, we aimed to comprehensively assess the current landscape of these diseases using population-based cancer registries that surveil the entire civilian population of the US. Importantly, this analysis includes all data from 2000 to 2017 and is therefore not subject to the impacts on cancer data reporting during the COVID-19 pandemic in the US. Methods: We accessed population-based data available from the year 2000 forward from Surveillance, Epidemiology, and End Results (SEER) and National Program of Cancer Registries (NPCR) registry networks to obtain information about incidence and outcomes of TGCT and OGCT. NPCR+SEER was utilized to characterize nation-wide patterns of incidence according to demographic features and histologic type, SEER21 to describe age-specific patterns, SEER18 to describe outcomes and SEER9 to describe long-term patterns of age-specific incidence according to year of diagnosis and year of birth. Detailed descriptive analysis were performed. Age-adjusted incidence rates (AAIRs) and temporal trends were calculated overall and stratified by race/ethnicity and histology. Observed and relative survival were also assessed overall and according to race/ethnicity and histology. Results: TGCTs were far more common than OGCTs and the majority of all GCTs occurred in adolescents and young adults. The AAIRs of TGCT were greatest in NH white men and for OGCT, greatest in Hispanic White women. Seminoma was the most common histology in TGCT, and dysgerminoma was most common in OGCT. For TGCT, the most drastic increases in incidence were noted in Hispanic and American Indian/Alaska Native men, whereas incidence was relatively stable in non-Hispanic white men. For OGCT, incidence was relatively similar amongst racial/ethnic groups. We also found that observed survival in Black men with TGCT is worse than all other racial/ethnic groups, but relative survival is comparable. A similar and more pronounced finding was seen in OGCT, but Black women experienced both worse observed and relative survival compared to the other groups. Regarding histology, those with seminoma or dysgerminoma had better survival than those with NSGCT/non-dysgerminoma. Conclusions: We present a contemporary and comprehensive assessment of incidence and outcomes of TGCT and OGCT for the entire US civilian population from 2000-2017, that is not subject to impacts of cancer reporting during the COVID-19 pandemic. We identified various racial/ethnic differences in incidence and survival both within and between TGCT and OGCT, which highlights opportunities to intervene.

Outcomes of immune-checkpoint inhibitor rechallenge in urothelial carcinoma: Results from a global real-world evidence study.

732 Background: Immune-checkpoint inhibitors (ICIs) have revolutionized the therapeutic landscape of urothelial carcinoma (UC) across clinical stages. Several ICIs have been approved by regulatory agencies for both adjuvant and metastatic settings. Limited information is available regarding the efficacy of rechallenge with ICI following progression on prior ICI-based therapy. We hypothesized that ICI rechallenge could be effective in selected pts with UC. Methods: A retrospective study was performed using the TriNetX analytics platforms for a large-scale search of patients (pts) with UC who underwent 2 lines of ICI (± other treatments between ICIs, either alone or in combo with other agents) at healthcare organizations collaborating through a TriNetX-mediated network across international sites. Descriptive statistics were used to summarize the clinical and demographic characteristics of pts. Kaplan-Meier analysis was used to estimate progression-free and overall survival (PFS, OS) with ICI rechallenge. Data were analyzed in October 2024. Results: From a total of 35,789 pts with UC, a cohort of 267 pts, treated with 2 sequential ICIs between 2014 and 2024, was identified (195M, 71F). The baseline median age was 73 years. Overall, 86% had bladder vs. 14% upper tract primary tumor. At initial diagnosis, 27% had stage IV, while 73% had stage I-III disease; 19% of pts had undergone radical cystectomy. 12% of pts were reported to have FGFR3 alterations, 12% PD-L1 positive. The median time on prior ICI was 19.5 months (mos - range: 16-27.5). The median time from the end of ICI to the start of ICI rechallenge was 6.4 mos. The most common ICI sequence was nivolumab followed by pembrolizumab (28.5%), then avelumab followed by pembrolizumab (22.4%), atezolizumab followed by pembrolizumab (20.8%), pembrolizumab followed by nivolumab (14.9%), pembrolizumab followed by avelumab (13.4%). The longest median (m)PFS was observed with anti-PD1 after anti-PD-L1 therapy (11.1 mos, range 0.89-38.4). The efficacy of ICI rechallenge was independent of the setting of prior ICI: perioperative vs. metastatic stage (p=0.16). mPFS with ICI rechallenge was 10.3 mos in pts treated with ICI ³12mos after the end of their prior ICI vs 6.0 mos in those rechallenged within &lt;12mos (p=0.15); mPFS was 9.0 mos in pts treated with ICI ³6mos after the end of prior ICI vs. 3.4 mos in those rechallenged within &lt;6mos (p=0.19). After a median follow-up of 22.7 mos, the mOS of ICI rechallenge was 25.8 mos. Conclusions: Although it is an uncommon strategy, ICI rechallenge after prior ICI-based therapy may benefit a subset of pts with UC, with outcomes varying based on the specific ICI regimen. Limitations include retrospective nature, variability in the timing of imaging across practices, and potential selection and confounding biases.

Phase I Trial of MCARH109, a G Protein–Coupled Receptor Class C Group 5 Member D (GPRC5D)–Targeted Chimeric Antigen Receptor T-Cell Therapy for Multiple Myeloma: An Updated Analysis

MCARH109 is a first-in-class G protein–coupled receptor, class C, group 5, member D (GPRC5D)-targeted chimeric antigen receptor (CAR) T-cell therapy for patients with relapsed/refractory multiple myeloma. This phase I clinical trial included 17 patients and determined that MCARH109 is safe at a maximum tolerated dose of 150 × 10 6 CAR T cells. In this updated analysis, no new serious adverse events were reported at a median follow-up of 37 months. Overall, 12 (71%) of 17 patients responded, including seven (70%) of 10 patients previously treated with B-cell maturation antigen-targeted therapy. The median duration of response was 8.6 months (95% CI, 5.7 to not reached [NR]) with two patients sustaining a stringent complete response at the time of last follow-up, 32 months and 41 months, respectively. The median overall survival (OS) was NR and the 3-year OS estimate was 59% (95% CI, 40 to 88). Possible GPRC5D loss via immunohistochemistry was observed in 6 (60%) of 10 patients at relapse. High-dimensional spectral cytometry–based immune profiling associated an activated T-cell phenotype at apheresis with a response to MCARH109.

Oxygen vacancy distribution and phase composition in scaled, Hf0.5Zr0.5O2-based ferroelectric capacitors

In this paper, we address correlations between film thickness, phase composition, and oxygen vacancy (VO) distribution in scaled, hafnia-based ferroelectric capacitors (FeCAPs), necessary to achieve low operating voltages, higher endurance, and advanced node integration. Using x-ray photoelectron spectroscopy, hard x-ray photoelectron spectroscopy, grazing incidence x-ray diffraction, and electrical characterization, we investigate the evolution of phase composition and VO profiles in Hf0.5Zr0.5O2 (HZO) films of 6 and 10 nm thickness. We demonstrate that thinner films exhibit a greater fraction of the non-polar tetragonal phase (t-phase), with increased VO concentration at the interface, affecting the device performance. Electrical measurements reveal contrasting wake-up and fatigue behavior between the two thicknesses, with thinner films showing decreased remanent polarization (2PR) due to t-phase dominance and VO redistribution during field cycling. These findings highlight the critical interplay of strain, phase stability, and VO dynamics, providing key insights for the optimization of HZO-based FeCAPs for advanced, low-power memory applications.

The effects of L-carnitine and fructose in improved Ham’s F10 on sperm culture in idiopathic severe asthenospermia within 24h

To study the effects of L-carnitine and fructose on semen parameters of severe asthenospermia patients by sperm culturing in vitro within 24h. We optimized the energy composition and antioxidant substances of sperm culture medium in vitro (based on Ham’s F10 culture medium) by orthogonal test for preparing high quality culture medium. Sperms of 60 patients with idiopathic severe asthenospermia were collected, and cultured in vitro within 24h, by Ham’s F10 culture medium added to different concentrations of L-carnitine and fructose and culture temperature, whose effects on sperm motility were observed to determine which is the most appropriate concentration and temperature. For determining the appropriate concentration of L-carnitine and fructose and the suitable culture temperature in Ham’s F10 culture medium, the orthogonal experiments were carried out to optimize above three factors, which had great influence on sperm viability, survival rate, deformity rate and DNA fragmentation index (DFI). The final concentration of L-carnitine and fructose was determined in terms of initial tests to assess the effects of different concentrations (4, 8, 12, and 16 mg/ml L-carnitine and 0.125, 0.250, 0.375, and 0.50 mg/ml fructose) on sperm viability and motility in culture. During the operation of processing and culturing sperms in vitro within 24h, orthogonal test showed that sperm viability was better at the final concentration of 8 mg/ml L-carnitine and 0.375 mg/ml fructose in improved Ham’s F10 culture medium at 36.5°C. Idiopathic severe asthenospermia sperm can be effectively improved by the modified Ham’s F10 culture medium of the final concentration of 8 mg/ml L-carnitine and 0.375 mg/ml fructose at 36.5°C within 24h, which has shown better culture effect and is superior to Ham’s F10 basic medium.

Comparative analysis of fungal and bacterial composition in natural wines and their closest pesticide-treated counterparts

Assess the journey: Characterizing muscle-invasive bladder cancer patients who receive neoadjuvant therapy and do not proceed with cystectomy.

746 Background: The standard treatment of muscle invasive bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC), offering a 5-10% survival benefit and reducing recurrence by 35%. However, little is known about the patients who start NAC but do not proceed to RC. In the SWOG-8710 trial, 18% of patients did not undergo surgery after NAC. Platinum-based regimens, while generally well tolerated, sometimes cause severe side effects. With increasing NAC use and evolving treatment options, some patients start NAC without completing definitive treatment. This study aims characterize patients who do not proceed with RC, focusing on their NAC experience and alternative treatments. Methods: A retrospective analysis was performed on MIBC patients recommended for neoadjuvant therapy followed by RC between 2020-2023 by a single provider at Stanford Health Care. Eligible patients had clinically localized bladder cancer (cT2-T4N0) who initiated neoadjuvant therapy and were deemed surgical candidates. Patients who were not platinum-eligible received alternative therapies on clinical trials . Data were collected on patient demographics, comorbidities, functional status, renal and hematologic function, and NAC administration. Patients who underwent cystectomy were excluded. Results: A total of 90 patients with MIBC who had a treatment plan involving neoadjuvant therapy followed by RC between 2020-2023 were identified. 22% (20/90) of these patients did not undergo cystectomy. The median age was 76, 75% male, 75% white. 50% of patients had variant or non-urothelial carcinoma histology. 60% were cT2 at time of initial consult. The majority of patients (80%) received platinum-based NAC, with only 4 receiving alternative therapies. One patient died of a stroke before completing NAC. The reasons for not undergoing RC were declining additional treatment (30%) and inability to tolerate surgery due to toxicity from therapy (30%), followed by patient preference of radiation therapy (20%), and disease progression (10%). Two additional patients were taken to the operating room; however, surgery was aborted due to unresectable disease and anesthetic complications. Among those who did not undergo RC, 42% opted for surveillance, 37% received trimodal therapy (TMT), and 21% received additional immunotherapy. Conclusions: In this study, we were able to gain a better understanding of our patient cohort who started neoadjuvant therapy but did not proceed to cystectomy. Reasons for this decision included toxicity related to neoadjuvant therapy, personal desire to forgo surgery, or prioritization of bladder preservation. These findings highlight the need for future efforts aimed at trying to predict this patient population and further comparative analysis of outcomes between this cohort and those who underwent cystectomy.

Prevalence of germline variants of uncertain significance in DNA repair genes and their potential impact on prostate cancer outcomes following radical prostatectomy.

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