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Impact of COVID-19 pandemic on the treatment of prostate cancer in Brazilian public health system, comparing pre and post pandemic data.

373 Background: During the COVID-19 pandemic resources from the Brazilian Public Health System (BPHS) were directed to the treatment of COVID-19. The impact of the pandemic on the treatment of prostate cancer in Brazil has not yet been rigorously evaluated. Methods: We compared the number of radical prostatectomies (RP), radiotherapy (RT), and hormonal (HT) and chemotherapy (CT) treatments from March 1st, 2020 to February 29th, 2022, with that of the two pre-pandemic years (March 1st, 2018, to February 28th, 2020). Additionally, we evaluated the post-pandemic period from March 1st, 2022 to February 28th, 2024. A large proprietary healthcare data science platform offered by TECHTRIALS was surveyed. Results: In the pandemic, 15,364RPs were performed in the BPHS, (U$14,271,297); there was a 23.3% reduction in the number of surgeries compared with the pre-pandemic years: 19,778RPs, (U$18,056,470). In the post-pandemic years 18,716 RPs were performed (U$ 18,373,781.92), an increase of 21.8% in those treated by surgery. In the pandemic, 34,922 men received RT (U$39,616,736), a 18.7% reduction in the number of patients as compared with the two pre-pandemic years, when 42,614 men were treated (U$44,148,190). In the post-pandemic years, 43,142 men received RT, an increase of 19% compared to the pandemic years (U$48,870,739.03). Regarding HT, 116,490 men were treated during the pandemic (U$74,834,615); in the pre-pandemic, 115,949 patients received HT (U$75,179,674). In the post-pandemic years, 127,602 men were treated with HT (U$80,078,824), an increment of 6.5% in cost and 10% in the number of patients treated compared to the pandemic years. As to CT for hormone-resistant disease, in the pandemic period 14,946 men were treated (U$23,402,947) compared with 12,695 men treated in the two pre-pandemic years (U$19,239,099). In the post-pandemic years 18,850 men were treated (U$33.571.073,40) an increment of 48.4% in number of patients treated and with an increase of 74% in costs compared to the pandemic period. Conclusions: During the pandemic years, there was a significant reduction of potentially curative treatments for prostate cancer in the BPHS. The number of systemic therapies increased, probably reflecting the policy of maintaining systemic therapies active during the pandemic. In the post-pandemic years, there was an increase in the number of systemic treatments, while RT and RP returned to a state very close to their pre-pandemic numbers. The impact of the COVID-19 pandemic on prostate cancer mortality in Brazil remains speculative.

Efficacy and safety of SABR with TKI and IO therapy in patients with mRCC.

529 Background: Metastatic RCC is a deadly disease and TKI in combination with IO has become a standard therapy for most patients. But some of the pts may present with oligo-metastasis and some with meta site related symptoms. SABR (Stereotactic Ablative Body Radiotherapy) has been proved to be highly effective for RCC in some studies and with potential immune-enhancing ability. The purpose is to investigate the efficacy and safety of SABR with TKI and IO therapy in pts with mRCC. Methods: This is an ambispective cohort study including pts receiving SABR with TKI and IO at the same time. The primary endpoint was PFS. Secondary endpoints included OS, ORR, DCR and TTTC (Time to treatment change). We also analyzed some of the pts’ gene characteristics to investigate the relationship between gene alterations and prognosis. Adverse events were evaluated according to CTCAE 5.0. Results: Until Aug 2024, we retrospectively analyzed pts from Mar 2020 to Mar 2024, and prospectively from Mar 2024 to May 2024. A total of 79 pts were included, of whom 72.2% were with ccRCC, 68.4% were with oligo-metastases (≤5 meta sites), and 83.5% were combined with SABR before 1st-line systemic therapy failure. All pts were categorized to IMDC intermediate or poor prognosis group and TKI and IO combination was used in all pts. All pts with oligo-metastases received SABR for all tumor sites and others were for cytoreductive purpose.The median follow-up was 20.3 mo. The mPFS was 28.6 mo and TTTC was 31.8 mo. The ORR was 68.4% and the DCR was 89.9%. The DCR of radiation lesions was 96.2%. The mOS was 44.8 mo. For pts received SABR before or after 1 st -line systemic therapy failure, the mPFS were 30.6 mo vs. 9.6 mo, respectively (p=0.004). In addition, The NGS analysis was performed in 25 pts tumor samples. The most frequent genes mutated were VHL (60%), SETD2 (24%), ARID1A (24%), TP53 (20%), PTEN (20%), TEF3 (16%), BAP1 (12%), RET (12%), and PBRM1 (12%). We discovered a favorable trend in the prognosis for PFS in pts with tumors purely driven by VHL loss. Mutations in the mTOR pathway genes, PTEN and HRR-related genes appeared to lead to poorer PFS. However, due to limited sample size, statistical significance was not reached. Grade 3 or above AE was 50.2%, and there was no treatment-related death. Conclusions: Targeted therapy combined with immunotherapy and stereotactic radiotherapy has achieved satisfactory survival results for mRCC, and early intervention by SABR may lead to a better PFS. Clinical trial information: ChiCTR2200059204 .

OPAR: A Randomized Trial of Partial Breast Irradiation in Five Fractions Once Daily for Early Breast Cancer

PURPOSE Previous studies suggest that external-beam partial breast irradiation (PBI) delivered twice a day can lead to increased adverse cosmesis (AC). The objective of our trial was to determine whether two regimens for PBI given once daily over 1 week resulted in acceptable AC to inform a phase III trial. METHODS Patients age ≥50 years with invasive breast cancer or ductal carcinoma in situ, ≤3 cm in size treated by lumpectomy with negative axillary nodes were randomly assigned to external-beam PBI of 30 Gy or 27.5 Gy, each given in five fractions once daily. The primary outcome was AC (fair or poor) by photographic assessment at 2 years. Secondary outcomes included AC assessed by nurse at 2 years, by patient self-assessment at 3 years, and late toxicity. On the basis of a 17% risk of AC with whole-breast irradiation, the upper bound of a two-sided 90% CI, 23% was set as the tolerance margin (OPAR, ClinicalTrials.gov identifier: NCT02637024 ). RESULTS In total, 142 patients were randomly assigned to 30 Gy and 139 to 27.5 Gy. The median follow-up was 5 years. The mean age was 65 years, and the mean tumor size was 1.2 cm. Both schedules met acceptability criteria by photographic assessment (AC, 12.1% [90% CI, 8.2 to 17.6] for 30 Gy and 15.2% [90% CI, 10.8 to 21.1] for 27.5 Gy) and by nurse assessment. AC by patient self-assessment exceeded the 90% CI for the 30 Gy regimen. At 5 years, 16 (11.3%, 90% CI, 7.6 to 16.4) patients treated with 30 Gy and eight (5.8%, 90% CI, 3.3 to 9.9) patients treated with 27.5 Gy were observed to have grade 2 or more late toxicity. CONCLUSION According to the study design, 30 Gy and 27.5 Gy resulted in acceptable cosmetic outcomes. In light of recent studies, a lower dose was chosen for the phase III trial.

High-power GeSn photodetector for 2-<i>μ</i>m RoF system

A radio-over-fiber (RoF) link simplifies the base station and network structure, adapting to the trends of high capacity and rapid development in modern communication. The development of 2-μm-band links improves the capacity of communication systems, which can solve future optical fiber capacity crises. In this work, a relaxed high-Sn-content GeSn absorption layer was grown on a Si substrate, and high-power GeSn photodetectors were fabricated. The photodetectors achieved a low dark current with a cutoff wavelength of about 2930 nm. The GeSn photodetectors had a saturated photocurrent of up to 70 mA operating in the 2-μm-wavelength range and a 3-dB bandwidth of approximately 1.6 GHz. The results provide a technical reference for the application of GeSn 2-μm detectors in RoF links.

Distinct water and phosphorus extraction patterns are key to maintaining the productivity of sorghum under drought and limited soil resources

Abstract Nutrient and water limitations contribute to yield losses in semi-arid regions. Therefore, crop rotations incorporating nitrogen-fixing legumes and drought-tolerant sorghum varieties offer a strategy to improve the utilization of scarce soil resources. Under semi-arid, field-like conditions, sorghum crop rotations with either cowpea pre-crop or fallow, including two early and three late maturing genotypes, were tested to identify stress adaptation traits of sorghum to water and phosphorus limitations. Morphological and physiological parameters were evaluated on a single-plant basis. Lower soil P content significantly delayed flowering compared to higher P levels. However, improved P availability arising from pre-crop residues reduced this effect. Mycorrhizal infection rates and root-to-shoot ratios were positively correlated with panicle N and P content at anthesis under low P conditions. Although drought significantly impacted yield, early maturing genotypes with the highest reduction in shoot biomass and reduced water use before flowering, could sustain yield production. Early-maturing genotypes characterized by high root-to-shoot ratios, rapid AMF establishment, and reduced water use before flowering exhibit a strong potential for maintaining yield and biomass production on nutrient-poor soils in semi-arid regions. Such genotypes conserve water before flowering and thus can alleviate post-flowering water stress, ensuring adequate P uptake despite low soil P availability.

Clinical outcomes in metastatic bladder cancer associated with mutations in Trithorax-group protein genes.

835 Background: The Trithorax-group (TrxG) comprises a large family of multi-protein complexes that play a key role in epigenetic regulation, cell division and inflammatory response; mutations therefore have a potential role as biomarkers or treatment targets. Two crucial complexes in TrxG are COMPASS (histone methylation) and SWI/SNF (chromatin remodeling). Certain genes in these complexes have been implicated as tumor suppressors and oncogenes, respectively. In urothelial cancer, mutations have been associated with more aggressive tumor biology, an immune-dysregulated microenvironment, and worse clinical outcomes. However, research into the overall impact of mutations in these complexes, particularly in metastatic setting, is scarce. We hypothesized mutations would predict worse outcomes following treatment, specifically investigating metastatic urothelial carcinoma (mUC). Methods: We retrospectively reviewed data from 63 patients with mUC treated at Brown Health Cancer Institute with next generation sequencing available from tumor or ctDNA. Demographic, pathologic, treatment and response data were collected. The presence of somatic alterations in the COMPASS complex ( KDM6A, KMT2B/C/D, SETD1/2, EP300 ) and SWI/SNF complex ( SMARCA2/4, SMARCB1, SMARCC1/2, ARID1A/B, ARID2 ) genes were noted. Log rank tests were used to analyze differences in overall survival (OS) and progression free survival (PFS) stratified by mutation status and first line treatments received. All outcomes were censored as of 12/31/22. Results: Of the 63 patients, the majority were male (41, 65%), white (57, 90%), had a smoking history (41, 65%). Median age was 74 (± 9.5). 28 (44%) received first-line chemotherapy and 31 (49%) received immune checkpoint inhibitor (ICI) monotherapy. 3 (5%) died prior to treatment and 1 (2%) entered a clinical trial. 41 (65%) had a mutation in any investigated TrxG gene; most common were KMT2D (17, 27%) and KDM6A (14, 22%). Patients with mutations were more likely to be older (75 vs 70, p = 0.04); there was no statistically significant difference in sex, smoking history, race, or sites of metastasis. The presence of a mutation was not associated with OS in the full cohort (median 14 months vs 13, p = 0.63, HR = 0.86 [0.45 – 1.6]). In the subset of patients who received first line chemotherapy, mutation presence (17, 61%) was associated with improved OS (21 months vs 10, p = 0.015, HR = 0.26 [0.08 – 0.77]) and PFS (7.9 vs 3.8, p = 0.051, HR = 0.36 [0.13 – 1.0]). Among patients who received first line ICI, mutation presence (19, 61%) had a trend for reduced PFS, (4.3 months vs 17, p = 0.06, HR = 2.2 [0.96 – 5.0]). Conclusions: Mutations in COMPASS and SWI/SNF genes were common in patients with mUC and associated with improved outcomes with 1st line chemotherapy and inferior responses to ICIs. TrxG mutations hold potential as predictive biomarkers, and merits further exploration in larger datasets.

Clinical outcomes of stage IIA/IIB seminoma treated with radiotherapy and chemotherapy: Should regional therapy be considered the preferred treatment approach?

629 Background: With the publication of the Surgery in Early Metastatic Seminoma Trial there has been increasing interest in the use of regional therapy as first line treatment (reserving systemic therapy for relapse) in patients with testicular seminoma with low volume with retroperitoneal lymphadenopathy. Herein, we sought to evaluate outcomes with both management approaches. Methods: A prospectively maintained single-institutional database was retrospectively queried for patients diagnosed between 1995-2016 with de novo clinical stage IIA/B (CSIIA/B) or who relapsed on surveillance (Rel-CSIIA/B) treated with radiotherapy or chemotherapy. All patients were reviewed by the multidisciplinary team; while the preferred management policy during this period was radiotherapy, all treatment decisions were individualized at the physician/patient level. Results: The median follow-up was 7.1 years (IQR 4.3-9.9). There were 153 patients: 67 had de novo CSIIA/B (IIA-32, IIB-35) and 86 patients had Rel-CSIIA/B seminoma (IIA-51, IIB-35). One hundred and twenty patients (78%) received radiotherapy (IIA-78, IIB-42) and 33 (22%) received platinum-based chemotherapy (IIA-5, IIB-28). Eleven patients (IIA- 9/78, IIB- 2/42) relapsed following radiotherapy and 1 patient (IIB) relapsed following chemotherapy, corresponding to 5-year relapse rates of 10% for radiotherapy and 3% for chemotherapy. All 12 patients who relapsed were treated successfully with salvage chemotherapy. Conclusions: Regional therapy in patients with testicular seminoma with low volume with retroperitoneal lymphadenopathy gives excellent treatment results – recognising that a small proportion of patients will need salvage chemotherapy for cure, thereby exposing these patients to the morbidity of two treatment strategies. Our results support the view that regional therapy is a reasonable treatment option in this setting and should be discussed with all patients.

Prognostic significance of PSA in the outcomes of patients with high risk localized prostate cancer.

347 Background: Patients diagnosed with localized high-risk prostate adenocarcinoma (LHRPC) with high Gleason scores (8-10) and prostate-specific antigen (PSA) levels ≤ 4 may experience an altered clinical course. In these patients, low PSA levels may reflect cellular dedifferentiation, indicating more aggressive tumor behavior despite appearing to have a low disease burden. We aim to investigate the impact of PSA levels in patients with LHRPC to better understand prognosis and optimize treatment strategies. Methods: We included patients diagnosed with LHRPC based on TNM stage (T1-T4, N0, M0) and Gleason 8–10 from 2004 to 2020, using data from the National Cancer Database. We stratified patients based on PSA levels (≤4 and &gt;4 ng/dl) and treatment approaches. We utilized Kaplan-Meier analysis and Cox proportional hazard model to study survival outcomes in patients with LHRPC. Results: We included 160,971 patients diagnosed with LHRPC, of which 86.69% (139,546) had PSA &gt;4 ng/dl, while only 13.31% (21,425) had PSA ≤4 ng/dl. Our cohort had 69.55% (111,953) patients aged ≥ 65 years and 30.45% (49,018) aged &lt; 65 years. Regarding race, the cohort was predominantly white, comprising 81.69% (131,497), followed by black at 14.47% (23,292), and other racial categories at 3.84% (6,182). In our cohort 34.43% (55,425) underwent surgery only (S), 9.62% (15,484) received radiation therapy only (RT), 46.81% (75,350) had radiation therapy combined with androgen deprivation therapy (RT + ADT), and 9.14% (14,712) received androgen deprivation therapy only (ADT). In our multivariate cox proportional hazard analysis, LHRPC patients with PSA &gt;4 ng/dL had a 7% (HR 0.93, 95% CI: 0.90–0.95; p&lt;0.001) decreased risk of death compared to those with PSA ≤4 ng/dL. Conclusions: In our study, LHRPC patients with PSA ≤4 ng/dL had poorer survival outcomes after adjusting for the treatment approach, race, age category, income, insurance status, facility type, and location. Further research is required to explore potential biological differences in patients with low PSA-secreting LHRPC. Cox proportional hazard analysis in patients with LHRPC, GS 8-10. Categories Hazard Ratio (95% CI) P-value Treatment type: Surgery only reference RT only 2.27 (2.19, 2.36) &lt;0.001 RT + ADT 2.37 (2.30, 2.44) &lt;0.001 ADT only 5.68 (5.49, 5.87) &lt;0.001 Charlson Deyson score : 0 reference &gt;=1 1.43 (1.40, 1.46) &lt;0.001 Facility type : Academic reference Non-Academic 1.20 (1.17, 1.23) &lt;0.001 PSA ≤ 4 ng/dl reference PSA &gt; 4 ng/dl 0.93 (0.90, 0.95) &lt;0.001

Real-world clinical practice gaps in timely homologous recombination repair gene mutation (HRRm) testing and poly (ADP-ribose) polymerase inhibitor (PARPi) treatment of patients with metastatic castration resistant prostate cancer (mCRPC).

85 Background: Testing for HRRm is standard of care for all mCRPC patients to identify those eligible to receive PARPi targeted therapy. Our previous real-world analysis of testing and treatment patterns (1/1/2020 – 12/31/2021) revealed 40.8% of mCRPC patients did not receive HRRm testing while 33.2% of HRRm positive (HRRm+) patients did not receive a PARPi. The approval of novel hormonal therapies (NHT) in combination with PARPi for first line treatment of mCRPC prompted us to expand our analysis, to determine timing of HRRm testing in relation to line of therapy (LOT) initiated, LOT when NHT and/or PARPi were received, and breakdown of HRRm+ genes in PARPi treated and untreated cohorts. Methods: The IntegraConnect – Precision Q de-identified database that includes electronic health and practice management data from 500 US sites of care was utilized to select a real-world cohort of newly diagnosed or treated mCRPC patients between 1/1/2020 - 12/31/2023. Patient charts were manually reviewed by medical curators to extract data including frequency and timing of germline and somatic testing for HRRm, testing success rate and results, and LOT where NHT and/or PARPi were received in the HRRm+ cohort. Results: Of the 1022 mCRPC total patients, 63.6% (n=650) received HRRm testing [21.2% germline (n=138); 58.8% somatic (n=382); 3.4% (n=22) germline + somatic; 16.6% (n=108) unknown]. Timing of HRRm testing revealed 19% (n=122) were tested at time of diagnosis, 41% (n=265) during or after first LOT, 22% (n=145) during or after second LOT, and 18% (n=118) at 3+ LOT. Only 9% (n=56) of patients had testing failures with 38% (n=21) originating from somatic tissue testing. Of the 38% (n=226) of HRRm+ patients, 58.4% (n=132) received a PARPi, including 13 patients receiving PARPi in &gt;1 LOT and 23% (n=33) receiving PARPi/NHA combination therapy. 65% (n=95) of patients received PARPi therapy after &gt;3 LOT. The HRRm+ genes in the PARPi treated cohort included BRCA2 (33.6%; n=51), ATM (30.9%; n=47), CHEK2 (13.2%; n=20), BRCA1 &amp; CDK12 (6.6%; n=10), PALB2 (5.3%; n=8), RAD54L (2%; n=3), BRIP1 , CHEK1 , &amp; RAD51B (0.7%; n=1). Of the 94 patients who did not receive PARPi therapy, 15.9% (n=17), 29% (n=31) and 3.7% (n=4) were BRCA2 , ATM , and BRCA1 mutation positive, respectively. Conclusions: This extended real-world analysis confirms clinical practice gaps with HRRm testing and receipt of matched PARPi therapy in mCRPC. 81% of patients do not receive HRRm testing at the time of mCRPC diagnosis and only 35% of HRRm+ patients receive PARPi prior to third LOT. It is particularly concerning that not all BRCA1/2 and ATM positive patients receive PARPi therapy. Continuing education and standardized testing practices may be needed to address these gaps.

Universal scaling of electrostatic effects of a curved counter-electrode on the emitter field enhancement

Experiments on field electron emission from single-tip nanoemitters have typically been carried out using a counter-electrode with a finite curvature radius R, positioned at a distance dgap from the emitter's apex. The effects of the counter-electrode's curvature on the apex field enhancement factor (γCa) of the emitter are still not understood. In this Letter, we theoretically explore how the apex field enhancement factor of an emitter, represented by a hemisphere on a cylindrical post (HCP) with apex radius ra=50 nm, is influenced by the curvature of a sphere-shaped counter-electrode. Importantly, our results show that for HCPs with sharpness aspect ratios typically between 102 and 103, there is a universal scaling such that γCa=γPaΨ(R/dgap), where γPa represents the apex field enhancement factor for the emitter assuming a planar counter-electrode, and Ψ(R/dgap) is a universal scaling function such that Ψ∼1 for R/dgap≫1 and Ψ∼(R/dgap)α, with α close to unity, for R/dgap≪1. These findings help partially explain discrepancies observed in orthodox field electron emission experiments, where it was reported that the effective γCa values extracted from the current–voltage characteristics of single-tip carbon nanotubes typically underestimate the theoretical γPa values when R∼dgap≫ra, a trend that is predicted by our results.

Genetic characterization and phylogenetic analysis of common house crows (Corvus splendens)

Efficacy outcomes 12 months after initiation of darolutamide in non-metastatic castrate resistant prostate cancer (nmCRPC) from the real world UK multi-centre RECORD study.

83 Background: Darolutamide has authorisation for treatment of non-metastatic Castrate Resistant Prostate Cancer (nmCRPC) based on the ARAMIS trial. The RECORD Study is a prospective real-world evaluation (RWE) of clinical outcomes in patients with nmCRPC treated with darolutamide in the UK. The study will improve understanding of treatment response and duration as well as inform regarding the use of next generation imaging (NGI) and effects of concomitant medication. Methods: Patients were enrolled from 19 centres over a 3-year period from November 2020. Data cut-off was 16 September 2024. Disease characteristics of patients and efficacy up to 12 months (m) after initiation of darolutamide are evaluated. Descriptive statistics will be used for patient demographics. Results: 257 patients were analysed with a median age of 77 (range 52-94) years (y). 52% have a Gleason score ≥8. 30 patients (11.7%) had NGI prior to initiation of darolutamide and 41 (15.8%) were on anticoagulant/antiplatelet medication. ECOG 0:35%, 1:59% and 2:6.2%. Median pre-treatment PSA was 9.7ng/mL and pre-treatment PSA doubling time (PSAdT) was 5 months. The greatest reduction in median PSA values was seen within the first 3m on darolutamide but was still decreasing slightly at 12m. PSA response was as follows: PSA 50 reduction at 3, 6, 9 and 12 months was 74%, 77%, 75% and 73% respectively and PSA 90 reduction at 3, 6, 9 and 12 months was 28%, 38%, 43% and 42% respectively. No differential effect on PSA reduction was seen with Gleason score (&lt;8, ≥8), PSAdT≤6m or &gt;6m, previous treatment (RT or prostatectomy), anticoagulant/antiplatelet medication or those who had NGI. Median duration of treatment on darolutamide did not significantly differ (p=0.067) in patients with PSAdT&gt;6m (104 patients) compared to those with PSAdT≤6m (135 patients). 46 patients (17.9%) have come off treatment within 12m of initiation: 26 (10.1%) disease progression, 8 (3.1%) toxicity (most frequent being fatigue and diarrhoea), 12 other unrelated causes including 1 death. Conclusions: This RWE shows that patients with nmCRPC in clinical practice have comparable outcomes to the ARAMIS trial. Response rates, tolerability and discontinuation rates are similar and in particular only 3.1% discontinuing treatment due to toxicity. Gleason score &gt;8; PSAdT and the use of NGI had no differential impact on PSA response. This is valuable RWE enabling optimisation of treatment in nmCRPC.

Survival disparities by sex with contemporary advanced urothelial carcinoma (aUC) therapy: A real-world analysis.

670 Background: Retrospective population data suggest poorer survival for female aUC patients. However, data on survival disparities in the era of immuno- and targeted therapies is limited. Methods: This cohort study used Flatiron Health’s nationwide de-identified electronic health record (EHR)-derived database. 7,244 patients (pts) were identified. Patients started on systemic therapy for aUC from 1/1/2017 to 5/1/2024, with reported sex, were included. Baseline demographics (including social determinants of health (SDOH) score), Eastern Cooperative Oncology Group performance status (ECOG PS), disease characteristics, treatment history, and clinical outcomes were abstracted. Progression free survival (PFS) and overall survival (OS) were compared between male and female patients, via Kaplan-Meier log-rank analysis and Cox proportional hazards models that included race, gender, and first-line therapy. Independent sample t-tests and chi-square analyses were used for univariate comparisons. P-values &lt; 0.05 were considered statistically significant. Results: A total of 3,045 pts with aUC were identified. 762 were (25.0%) female. In 1L, 28% received immunotherapy (IO) monotherapy, 3.4% received enfortumab vedotin+pembrolizumab (EVP), 37% received carboplatin (carbo), 28% cisplatin (cis), and 6% other chemotherapy (p=0.814). Females were more like to have ECOG PS&gt;1 at diagnosis (p=0.020). Greater SDOH score was not associated with sex (p&gt;0.1). Female sex was associated with inferior 1L PFS (median 4.3 vs 4.6m; HR 1.14, p=0.04) but no difference in OS (6.4 vs 6.5m; HR 1.01, p=0.2). Females had inferior PFS to men on Cox multivariable analysis when adjusting for race and first line therapy (p=0.006). On Cox univariate analysis stratified by 1L treatment, PFS was comparable between sexes on carbo (n=1127; p=0.4), cis (n=856; p=0.2) and EVP (n=25, p= 0.7), but women had inferior PFS to men on IO (n=595, p= 0.01). Women had comparable OS to men among all 1L treatments. Conclusions: In a large real-world database, female aUC patients had inferior PFS but comparable OS to males. Among 1L treatments, only immunotherapy was associated with inferior PFS for females vs. males. Baseline characteristics and survival in males vs. females. Male (n=2283) Female (n=762) Sig (p) Baseline Characteristics ECOG PS 0-1 (%) 64.1 60.6 0.020 2-4 (%) 15.2 17.8 Treatment at Academic Center (%) 19.1 18.0 0.360 SDOH score 3.13 3.07 0.110 1L Treatment IO (%) 27.7 28.1 0.814 EVP (%) 3.3 3.7 Carbo (%) 37.3 36.2 Cis (%) 27.5 28.9 Other (%) 6.6 6.1 Survival mPFS (m) 4.6 4.3 0.040 mOS (m) 6.5 6.4 0.200 Sig. values in bold (p&lt;0.05).

A phase 1b study of cabozantinib and nivolumab with abiraterone (CABIOS) in metastatic castration-sensitive prostate cancer (mCSPC): Updated safety, efficacy, and immunologic findings.

186 Background: Standard of care for mCSPC typically includes androgen deprivation (ADT) with novel hormonal agents +/- docetaxel. CABIOS is a phase Ib single-arm trial of cabozantinib + nivolumab + abiraterone/prednisone (cabo, nivo, abi/pred) in mCSPC (NCT04477512). Preliminary safety and efficacy data were previously reported. Methods: Eligible patients (pts) had de novo or recurrent mHSPC with &lt; 12 weeks ADT prior to enrollment, ECOG 0-1, and adequate end organ function. Further details on trial design were previously reported. The primary endpoint is safety and tolerability. Secondary endpoints include overall survival (OS), progression free survival (PFS), PSA response, and failure-free survival (FFS; defined as any one of clinical, PSA, or radiographic progression, or new treatment start). Exploratory analyses include CyTOF of peripheral blood and multiplex serum cytokine ELISA. Results: The trial is closed to accrual. 18 pts enrolled between 2/2021 and 3/2023 received treatment and are included in the analysis. Median follow-up is 32 months. There were no dose-limiting toxicities (DLTs). Gr 3-4 treatment related adverse events (TRAEs) occurred in 8 pts. The most common serious TRAEs were AST/ALT elevation (4), diarrhea (3), and hypertension (3). Treatment continued for or beyond study duration (two years) in 6 pts. Treatment was stopped in 12 pts due to adverse events (6), progression (5), and patient preference (1). Median OS and PSA PFS have not been reached. Nine of 18 pts had an FFS event at a median of 15.6 months compared with a median censored FFS of 32.2 months to-date in the remaining pts. CyTOF analyses of peripheral blood revealed a significant increase in effector cytotoxic CD8+ T-cells, total NK cells and CD16 hi cytotoxic NK cells post- compared with pre-treatment. Conversely, regulatory CD4+ and CD8+ T-cell as well as Th17 cell populations were significantly decreased in peripheral blood post-treatment. Furthermore, a marked reduction in free-active TGF-β and soluble LAG3 were observed in serum post vs. pre-treatment. We compared pre-to-post fold changes in these populations between patients who have and have not experienced treatment failure (FFS). Early treatment failure was associated with reduced innate lymphoid cells and increased total B-cells. Conclusions: Here, we present updated clinical and immune correlative findings of the first trial of cabozantinib in combination with nivolumab in mCSPC patients receiving ADT and abi/pred. Overall, the trial showed acceptable safety/tolerability with no DLTs. Grade 3+ TRAEs were seen in 44% of patients. Correlative data suggest a favorable peripheral immunomodulation by the treatment combination with a reduction in suppressive soluble factors and increase in effector immune populations. Future studies will evaluate the tumor microenvironment. Clinical trial information: NCT04477512 .

Impact of Medicare Advantage (MA) on timely hormonal intensification in metastatic hormone sensitive prostate cancer.

166 Background: As MA plans gain popularity, covering over half of eligible beneficiaries in 2023, concerns have arisen about their ability to manage complex cancer care due to pre-authorization requirements and limited physician networks. The study compares MA and Traditional Medicare (TM) in delivering timely hormonal intensification, specifically through addition of oral novel hormonal therapy (NHT) to castration therapy, which became central part of treating metastatic hormone-sensitive prostate cancer (mHSPC) by 2018. Methods: We utilized nationwide Flatiron Health Electronic Health Record-derived de-identified database to include patients diagnosed with mHSPC on or after 2018 (when abiraterone was approved for mHSPC treatment). Eligible patients were &gt;=65 yr old, had at least one clinic visit within six months of diagnosis, and were covered by either MA or TM. Multivariable logistic regression with Inverse Probability Weighting, adjusting for socioeconomic status (SES), age, race, ECOG, and year of diagnosis, assessed the impact of insurance type on likelihood of initiating NHT within 30, 45, and 90 days of diagnosis (defined as date when the patient began taking prescribed NHT, within the period of interest). Results: 4078 patients &gt;=65 yr old diagnosed with mHSPC after 2018 were identified in Flatiron database; of these 2261 had at least one clinic visit and were enrolled in either MA or TM plans. Most patients were White, aged 75-85, having better SES (SES 4 or 5), de novo mHSPC, and from community hospitals (Table 1). Among the 1752 (77%) patients who received NHT, 1060 (61%) had TM, and 692 (39%) had MA. In adjusted analysis, TM patients were more likely than MA patients to initiate timely NHT intensification within 45 days of mHSPC diagnosis (OR: 0.85; 95% CI: 0.74-0.99). No significant differences were found for NHT initiation at 30 (OR: 0.88; 95% CI: 0.74-1.06) or 90 days (OR: 1.06; 95% CI: 0.93-1.22). Subgroup analyses showed significantly more delays in MA compared to TM among patients with lowest SES and racial minorities. Conclusions: Patients with TM showed a trend toward earlier NHT intensification compared to those with MA. This suggests a need to further examine MA and its impact of pre-authorization and network limitations on equitable high quality cancer care. Key baseline characteristics and outcome comparisons between mHSPC patients enrolled in TA and MA. TA N (%) MA N (%) P Race Asian 21 (2%) 13 (2%) &lt;0.001 Black 91 (7%) 91 (10%) Hispanic/Latino 39 (3%) 49 (6%) White 932 (67%) 527 (60%) Other 299 (22%) 199 (23%) ECOG 0/1 958 (69%) 635 (72%) 0.11 2 125 (9%) 69 (8%) 3/4 23 (2%) 23 (3%) Unknown 276 (20%) 152 (17%) SES 1 147 (11%) 113 (13%) &lt;0.001 2 209 (15%) 167 (19%) 3 248 (18%) 189 (22%) 4 347 (25%) 198 (23%) 5 316 (23%) 149 (17%) Unknown 115 (8%) 63 (7%) Initiation of Hormonal Intensification OR (95 CI) P 30 days 1* 0.88 (0.74 - 1.06) 0.18 45 days 1* 0.85 (0.74 - 0.99) 0.04 90 days 1* 1.06 (0.93 - 1.22) 0.37 *Reference.

Enhanced piezoelectricity in TiSXY monolayers based on electronegative polar moments effect

It is a challenge to find the relationship between the microscopic property of atoms in monolayers and the macroscopic piezoelectricity of monolayer. By first-principles calculation, we find not only the super-dipole moment (SDM) effect but also the electronegative polar moments (EPMs) effect, which can lead to the remarkable piezoelectricity in TiSXY monolayers. The SDM and EPM effects can deepen the understanding of the piezoelectric physical mechanism and provide the design strategy for ultrathin nano-devices.

Identifying invasiveness to aid lung adenocarcinoma diagnosis using deep learning and pathomics

Association between PD-1 expression on tumor-infiltrating regulatory T cells and resistance to first-line nivolumab in advanced clear cell renal cell carcinoma: Insights from the HCRN GU16-260 clinical trial.

590 Background: Inhibition of PD-1 signaling in regulatory T cells (Tregs) has been shown to enhance their immunosuppressive function. We previously demonstrated that high levels of PD-1 expression on tumor-infiltrating Tregs are associated with resistance to nivolumab (nivo) monotherapy in pretreated patients with advanced clear cell renal cell carcinoma (ccRCC) from the CheckMate-025 trial (Denize et al, 2024). Here, we aim to validate these findings in the first-line setting. Methods: Primary tumor tissues from patients with ccRCC (n=70) treated with first-line nivo in the HCRN GU16-260 clinical trial were analyzed using multiparametric immunofluorescence (IF). The percentage of tumor-infiltrating PD-1+ Tregs was quantified by image analysis. Associations with objective response rate (ORR) and progression-free survival (PFS) were evaluated using logistic and Cox regression models, along with Fisher’s exact test and log-rank test for statistical inference, as appropriate. The alpha level was set at 5% (one-sided). Results: In line with our previous findings, the percentage of PD-1+ Tregs, measured as a continuous variable, did not have a statistically significant association with PFS [HR = 2.62; p = 0.169] or ORR [OR = 0.72; p = 0.42]. Using an optimized cut-off based on the minimal p-value for ORR, patients with a high percentage (≥36%) of PD-1+ Tregs (8/70) experienced shorter median PFS (3.4 vs. 10.9 months; p = 0.001) and a trend toward lower ORR (12.5% vs. 43.6%; p = 0.093) compared to those with a low percentage (62/70). Conclusions: PD-1 expression on tumor-infiltrating Tregs is associated with worse outcomes to first-line nivo therapy in patients with advanced ccRCC, confirming our previous findings. These results highlight the therapeutic potential of targeting Tregs to overcome resistance and improve the efficacy of PD-1 blockade, which is currently being evaluated in a clinical trial (HCRN GU22-587).

Impaired renal function and cisplatin-based regimens as risk factors for neoadjuvant chemotherapy-induced acute kidney injury in muscle-invasive bladder cancer: A multicenter retrospective study.

760 Background: Neoadjuvant chemotherapy (NAC)-induced acute kidney injury (AKI) is one of the frequent complications in patients with muscle-invasive bladder cancer (MIBC) and we previously have reported the negative impact of NAC-induced AKI on oncological outcomes. However, its risk factors remain unclear. Methods: This multi-institutional retrospective study included 517 patients with MIBC who received 2–4 cycles of NAC followed by radical cystectomy. AKI was defined according to the KDIGO criteria. Patients were divided into two groups: patients who developed any stage AKI during NAC (AKI group) and patients who did not (non-AKI group). Multivariable logistic regression analysis was performed to identify the risk factors for NAC-induced AKI. The predictive abilities for AKI were evaluated using the area under the receiver operating characteristic (ROC) curve. Results: The median age was 69 years. Of the 517 patients, 188 (36%) received cisplatin-based regimens and 92 (18%) developed any stage AKI. Approximately 86% AKI were stage 1 AKI. eGFR in the AKI group was significantly lower than that in the non-AKI group ( P &lt;0.001). The rate of AKI development in patients who received cisplatin-based regimens was significantly higher than that in patients who received carboplatin-based regimens ( P &lt;0.001). In the multivariable analysis, hypertension, impaired renal function, and cisplatin-based regimen were independently and significantly associated with increased risk of AKI (Table). The optimal cutoff value of estimated glomerular filtration rate for AKI was 65.0 mL/min/1.73m 2 . ROC analysis showed that the area under the curve (AUC) of hypertension plus eGFR &lt;65.0 mL/min/1.73m 2 plus cisplatin-based regimen was 0.748 (95% confidence interval: 0.697–0.799). Conclusions: Hypertension, impaired renal function, and cisplatin-based regimens were risk factors for NAC-induced AKI in patients with MIBC. Multivariable analysis for AKI development. Factor P value Odds ratio 95% CI Age Continuous 0.462 0.989 0.959–1.019 Hypertension Presence 0.016 1.894 1.128–3.179 eGFR Continuous &lt;0.001 0.955 0.939–0.971 Cisplatin-based regimens Positive &lt;0.001 6.530 3.725–11.45

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