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Cost analysis of corneal tissue processing: A scoping review protocol

Introduction Diseases affecting the cornea are a group of pathological conditions responsible for the main causes of blindness worldwide. Corneal transplantation aims to replace dysfunctional corneal tissue with a transparent tissue graft obtained from a deceased donor, which enables the full recovery of lost vision. Processes are initially performed to prepare the corneal tissue for transplantation in order for this transplant to be viable. There is a gap in knowledge regarding the costs of these processes. This review aims to carry out a robust, broad and current mapping of studies which analyze the costs of processing corneal tissue for transplantation. Objective The objective of this study is to map the evidence produced in the literature on cost analysis studies of corneal tissue processing. Materials and methods A scoping review will be conducted to map the topic, gather different research designs and identify the available scientific evidence on corneal tissue processing. To this end, a scoping review protocol was developed, registered in the Open Science Framework (accessed at: DOI 10.17605/OSF.IO/2X89U), following the good practices described by the Joanna Briggs Institute. The review report will be guided by the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews checklist. The data will be presented descriptively, with a summary of the studies found. The guiding research question of the study is: What is the scope of scientific evidence on the cost analysis of corneal tissue processing for transplants?

Nutrients, bioactive compounds and antinutritional properties of marigold genotypes as promising functional food

Prognosis in metastatic renal cell cancer (mRCC) with major venous involvement (MVI): A population-based study.

454 Background: Limited data exist on outcomes in mRCC patients with major venous involvement (MVI). Assessment of impact of a given variable on prognosis in cancer patients is challenging given competing causes of death (PMID: 25417239). This analysis aims to estimate cancer prognosis in mRCC patients with MVI, considering death from competing causes. Methods: Data from the Surveillance Epidemiology and End Results (SEER) database (2010-2020) were analyzed for survival and mortality in mRCC patients with MVI. 5-year (y) overall survival (OS) and 5-y probability of cancer death were calculated using the actuarial method in SEER*Stat 8.4.4, reported as percentages with 95% confidence intervals (CI). Results were based on the site of MVI (renal vein, inferior vena cava [IVC]) and stratified by age (<65, >65 years), gender (male, female), and race/ethnicity (Non-Hispanic [NH] White, NH Black, NH Asian/Pacific Islander [API], Hispanic). Results: A total of 89047 mRCC patients were included in our analysis of whom 10785 (12%) had major venous involvement (MVI). Overall, patients who experienced MVI had worse prognosis as compared to those who did not have MVI (5-y OS: 53.2% vs 84.4% and 5-y cancer death: 38.6% vs 8.2% respectively). Among cohort with MVI, prognosis was poor with IVC involvement as compared to involvement of renal vein (5-y OS: 36% vs 57%; 5-y cancer death: 56% vs 35% respectively). Patients who had the worst prognosis with MVI included older adults (>65 y) (5-y OS: 47.8%; 5-y cancer death: 40.8%) and NH Black (5-y OS: 41.5%; 5-y cancer death: 49.8%) (Table). Conclusions: Prognosis in mRCC with MVI, especially with IVC involvement, was poor, particularly for older adults (>65 y) and NH Black patients. Further research is needed for better prognostication and risk stratification to improve outcomes for high-risk patients. Subgroup No MVI MVI N 5-year OS (%), 95% CI 5-year Cancer death (%), 95% CI N 5-year OS (%), 95% CI 5-year Cancer death (%), 95% CI Overall population 78,262 84.4 (84.1-84.7) 8.2 (8.0-8.4) 10,785 53.2 (52.0-54.3) 38.6 (37.5-39.7) Age <65 y 49,217 89.0 (88.6-89.2) 6.5 (6.3-6.8) 5,897 57.5 (56.0-59.0) 36.8 (35.4-38.3) >65 y 29,045 77.0 (76.1-77.2) 10.9 (10.5-11.4) 4,888 47.8 (46.0-49.5) 40.8 (39.2-42.4) Gender Male 49,221 83.0 (82.7-83.5) 8.9 (8.6-9.2) 7,503 53.2 (51.8-54.6) 38.3 (37.0-39.6) Female 29,041 86.5 (86.0-86.9) 7.0 (6.7-7.4) 3,282 53.0 (51.0-55.0) 39.4 (37.4-41.3) Race/ethnicity NH White 49,520 84.0 (83.7-84.4) 8.3 (8.0-8.5) 7,182 53.5 (52.1-54.8) 38.0 (36.7-39.3) NH Black 8,878 82.0 (81.0-82.9) 8.1 (7.5-8.8) 685 41.5 (37.1-45.9) 49.8 (45.4-54.1) NH API 4,747 86.0 (85.1-87.4) 8.5 (7.6-9.4) 713 52.9 (48.2-57.3) 39.9 (35.5-44.1) Hispanic (All Races) 13,826 86.5 (85.8-87.2) 7.9 (7.4-8.4) 2,014 56.2 (53.4-58.8) 36.7 (34.1-39.2) N: number of cases; OS: overall survival; CI: confidence interval; NH: Non-Hispanic; API: Asian/Pacific Islander; MVI: major venous involvement.

Interim analysis of the “shutter speed” MRI model to detect clinically significant prostate cancer.

339 Background: Prostate cancer (PCa) MRI can fail to identify high-grade lesions, and mis-grade lesions, up to 30% of the time. Objective imaging techniques are needed to better discern aggressive from indolent PCa. While the dynamic contrast enhanced (DCE) sequence of mpMRI has not played a routine role in identifying clinically significant PCa (csPCa), improvements in DCE may aid in the detection of cancers with weak signals on other MRI sequences. We studied the ability of “Shutter Speed” MRI (SSMRI), a technique based on DCE including objective measurements of perfusion, to detect csPCa lesions and adverse pathology. Methods: We analyzed PCa lesions from patients who underwent standardized MRI (Siemens VIDA 3T, endorectal coil; planned n=124) followed by radical prostatectomy with whole-mount histopathology (n=95). An experienced GU pathologist annotated lesion size and Grade Group (GG). An experienced radiologist reviewed all mpMRI lesions, and the SSDCE parameters were measured post-acquisition using a standardized software package. This paired data analysis compared the ability of SSMRI (SSDCE, T2, DWI) and mpMRI (standard DCE, T2, DWI) to detect csPCa lesions (ISUP ≥ GG 2, ≥5mm) or adverse pathology (extracapsular extension [ECE], seminal vesical invasion [SVI], lymph node invasion [LNI], GG≥4, or their composite [CO]) using logistic regression. We constructed receiver operator characteristic curves (ROC), and AUC was compared for the detection of csPCa (primary endpoint) and adverse pathology (secondary endpoint) (Table). Results: Patient mean age and PSA at diagnosis were 64.6 years and 9.7 ng/mL respectively. 91 lesions were assessed, of which 25 met criteria for csPCa. When comparing ROC for detection of csPCa, SSDCE improves the AUC of DCE alone from 0.72 (95% CI 0.50-0.95) to 0.83 (95% CI 0.71-0.95), and when added to mpMRI improves the AUC from 0.80 (95% CI 0.75-0.86) to 0.94 (95% CI 0.88-1.00) (p <0.0001). While the AUC improved by 0.13 for the detection of SVI when SSDCE was added to mpMRI, this did not reach statistical significance, nor did it for any other adverse feature. Conclusions: SSMRI significantly enhanced the detection of csPCa lesions. A larger cohort is needed to assess SSMRI’s ability to detect adverse pathology. These findings further the efforts toward earlier and more accurate diagnosis of csPCa. Comparison of AUC: Addition of SS to DCE and mpMRI. Methods and AUC (95%CI): DCE SSDCE mpMRI SSMRI P value csPCa 0.72 (0.50-0.95) 0.83 (0.71-0.95) 0.80 (0.75-0.86) 0.94 (0.88-1.00) P<0.0001 ECE 0.64 (0.50-0.79) 0.63 (0.48-0.78) 0.70 (0.59-0.81) 0.72 (0.59-0.86) P=0.66 SVI 0.75 (0.61-0.89) 0.75 (0.60-0.90) 0.71 (0.60-0.83) 0.84 (0.72-0.96) P=0.12 LNI 0.64 (0.48-0.79) 0.59 (0.42-0.76) 0.71 (0.62-0.81) 0.73 (0.57-0.88) P=0.88 GG≥ 8 0.67 (0.50-0.83) 0.63 (0.45-0.82) 0.67 (0.56-0.79) 0.74 (0.57-0.91) P=0.23 CO 0.66 (0.51-0.81) 0.62 (0.46-0.78) 0.70 (0.58-0.81) 0.71 (0.56-0.85) P=0.67

INTerpath-004: A phase 2, randomized, double-blind study of adjuvant pembrolizumab (pembro) with V940 (mRNA-4157) or placebo for renal cell carcinoma (RCC).

TPS610 Background: The PD-1 inhibitor pembro is approved as monotherapy for the adjuvant treatment of patients with RCC at increased risk of recurrence following nephrectomy or nephrectomy and resection of metastatic lesions based on results from the phase 3 KEYNOTE-564 trial. Novel combination strategies could provide further clinical benefit in the adjuvant setting. V940 (mRNA-4157) is an individualized neoantigen therapy hypothesized to work in synergy with immune checkpoint inhibitors by generating de novo tumor-specific T-cell activity. V940 + pembro showed improved clinical outcomes for stage III/IV melanoma compared with pembro alone in the phase 2b KEYNOTE-942 study. INTerpath-004 is a global, multicenter, randomized, double-blind, phase 2 trial (NCT06307431) designed to evaluate the efficacy and safety of adjuvant pembro + V940 or placebo in patients with RCC who have undergone nephrectomy. Methods: Eligible patients are adults with histologically or cytologically confirmed RCC with clear cell or papillary histology (intermediate-high risk [pT2 Gr4, N0, M0 or pT3 Gr3/4, N0, M0], high risk [pT4, N0, M0 or pT any stage, N1, M0], or M1 NED [solid, isolated, soft tissue metastases that can be completely resected at the time of nephrectomy or ≤2 years from nephrectomy]) with or without sarcomatoid features. Patients must have undergone nephrectomy and/or metastasectomy ≤12 weeks prior to randomization and be tumor-free as assessed by investigator. Patients must not have received prior systemic therapy ≤4 weeks or radiotherapy ≤2 weeks prior to randomization. Approximately 272 patients will be randomly assigned 1:1 to receive pembro 400 mg intravenously every 6 weeks for ≤9 cycles in combination with either V940 1 mg or placebo intramuscularly every 3 weeks for ≤9 doses or treatment discontinuation due to unacceptable toxicity, disease recurrence, patient withdrawal, or investigator decision. Randomization will be stratified by histology (clear cell vs papillary) and disease risk (intermediate-high vs high vs M1 NED). Imaging assessments (computed tomography or magnetic resonance imaging) will be performed every 12 weeks through year 2, every 16 weeks in years 3-5, and every 24 weeks in year 6 and beyond. The primary endpoint is disease-free survival by investigator assessment. Secondary endpoints include distant metastasis-free survival, overall survival, and safety parameters, including adverse events (AEs), laboratory test results, and vital signs. AEs will be monitored throughout the study and for 30 days after the last dose of treatment (90 days for serious AEs) and graded per National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Efficacy will be assessed in all randomly assigned patients, and safety will be assessed in all patients who received ≥1 dose of study intervention. Recruitment is ongoing. Clinical trial information: NCT06307431 .

Which patients with metastatic hormone-sensitive prostate cancer (mHSPC) benefit more from androgen receptor pathway inhibitors (ARPIs)? STOPCAP meta-analyses of individual participant data (IPD).

20 Background: Clinical features of people with mHSPC may affect their outcomes from the addition of ARPIs to androgen deprivation therapy (ADT). The STOPCAP Collaboration is seeking IPD to reliably investigate potential ARPI effect modifiers and determine who benefits more from an ARPI vs docetaxel plus ADT doublet. Methods: Full methods are in registered protocols (CRD42023431331; CRD4202540066). We sought IPD for completed trials examining effects of ARPIs for mHSPC. Initially, we examined ARPI effects using intention-to-treat, two-stage, common-effect meta-analysis of hazard ratios (HRs), adjusted for a core set of covariates and use of concomitant docetaxel. Main effects were based on overall survival (OS). Interaction effects were based on progression-free survival (PFS) to maximise power, then OS whenever PFS interactions were found (P<0.10). Within clinically-relevant subgroups, ARPI and docetaxel doublet effects were compared using two-stage, contrast-based, random-effects network meta-analysis (NMA). Results: By October 2024, we had updated IPD from five trial comparisons: LATITUDE, STAMPEDE A vs G, SWOG-1216, ENZAMET, and STAMPEDE A vs J. Based on these (2882 events/5472 pts), adding an ARPI to ADT improved OS (HR=0.69, 95% CI=0.64-0.74). Four trial comparisons (excluding SWOG-1216) provided PFS data (2781 events/4161 pts) and showed improved PFS (HR=0.49, 95% CI=0.45-0.53). The relative benefit of ARPIs on PFS increased with younger age (interaction p=0.034), higher BMI (interaction p=0.048), and lower burden of metastases (interaction p=0.096). These effects were similar for OS (age interaction p=0.035; BMI interaction p=0.031; volume interaction p=0.25). The age effect was most pronounced in the abiraterone trials. Combining IPD from the ARPI + ADT and docetaxel + ADT trials (GETUG-AFU-15, CHAARTED, STAMPEDE A vs C) in NMA suggested that overall, an ARPI doublet may improve OS more than a docetaxel doublet (HR=0.85, 95% CI=0.70-1.03). However, when the NMA was confined to participants with high-volume, synchronous disease, where docetaxel is most efficacious (but excluding SWOG-1216, for which these data were not available), effects on OS were: HR=0.89, 95% CI=0.74-1.06. Conclusions: Our preliminary results suggest that people with mHSPC who are younger, have a higher BMI, or have low volume disease, may benefit more from ARPIs. ARPI and docetaxel doublets seem similarly effective in high-volume, synchronous disease. We will present updated analyses, incorporating recently received PEACE 1 IPD, for a clearer picture of ARPI effects, including subgroup-specific effects. Ongoing collection of IPD from other key trials will allow robust comparison of ARPI doublet with triplet therapy (including docetaxel), guiding more personalised treatment.

A multicenter cross-sectional survey of the role of community pharmacists, attitudes, and perceptions in preventing and controlling cardiovascular diseases

Background Cardiovascular diseases are a leading cause of mortality globally and impose suffering and economic difficulties, particularly in low- and middle-income countries. Community pharmacists present an opportunity for effective prevention and control of cardiovascular diseases. The overarching aim of the study was to evaluate factors associated with the extent of involvement, barriers and facilitators, and perceptions of Lesotho community pharmacists in preventing and controlling cardiovascular diseases. Methods The study utilised a quantitative cross-sectional survey. A semi-structured questionnaire was distributed to licensed community pharmacists across four districts between March and July 2023. Parametric and non-parametric tests were performed for data analysis using a Statistical Package for Social Sciences version 26. Results Apart from medicine dispensing, community pharmacists were mostly involved in hypertension (mean = 4.38±.73) and diabetes (mean = 4.17±.91) screening, weight management advice (mean = 3.81±.87), disease education (mean = 3.93±.83), medication management therapy (mean = 3.74±.99, 3.81±.88), referral of and follow up on patients (mean = 3.70±.98 and 3.87±.92). There was a significant association between the extent of involvement and pharmacy location, experience of community pharmacists, availability of tools, number of patients seen daily, and presence of other healthcare professionals at a community pharmacy (p<0.05). The most common barriers were related to patient factors (>75% agree to strongly agree), such as lack of awareness of community pharmacists’ services. Community pharmacists possessed positive (mean >3) attitudes and perceptions regarding their role in cardiovascular disease management. Conclusions Besides dispensing medicine, community pharmacists had varying extent of involvement in health promotion activities. The provision of these services differed between socio-demographic groups. Community pharmacists possessed good knowledge, positive attitudes towards their cardiovascular disease management role. Thus, they can improve cardiovascular disease outcomes. However, the barriers potentially limit their scope of practice and encourage inconsistent community pharmacy services. The findings present pertinent information to policy-makers, regulators, and pharmacists that can inform the development of frameworks to improve clinical and pharmacy practice in Lesotho and low- and middle-income countries.

Evaluation of methylene blue restaining versus conventional hydrogen peroxide decolorization in immunohistochemical diagnosis of melanoma

Abstract This study seeks to address the challenge of melanoma identification in immunohistochemical (IHC) diagnosis, which is complicated by the similar coloration of melanin and DAB (Diaminobenzidine) staining, by introducing methylene blue counterstaining as an innovative solution. We compared the effectiveness of methylene blue counterstaining with that of the traditional hydrogen peroxide bleaching method in the diagnosis of melanoma. The study included 46 paraffin-embedded melanoma samples, and the staining efficacy for markers such as Melan A, HMB-45, PRAME, and Ki-67 was assessed via both methods. The results demonstrated that methylene blue counterstaining effectively converted the brownish-yellow melanin granules to a deep green color, significantly enhancing contrast and clarity with DAB staining. The average contrast and clarity scores for the methylene blue counterstaining method were 1.96 ± 0.21 and 1.91 ± 0.28, respectively, which were significantly greater than those of the conventional IHC group and the hydrogen peroxide bleaching group (P < 0.01). Furthermore, methylene blue counterstaining did not cause noticeable tissue damage or cellular morphology distortion, with tissue integrity scores comparable to those of the conventional IHC group (P > 0.05). Although the contrast and clarity also improved in the hydrogen peroxide bleaching group, it resulted in a significant decrease in tissue integrity (P < 0.01). This study is the first to apply methylene blue counterstaining in melanoma IHC analysis, demonstrating its advantages in enhancing staining quality, simplifying procedural workflows, and preserving antigenicity. This method provides a novel and effective tool for the pathological diagnosis of melanoma, potentially improving diagnostic accuracy and reliability.

Evaluation of post radiotherapy PSA as a prognostic and predictive biomarker in high risk prostate cancer: A secondary analysis of RTOG 0521.

384 Background: RTOG 0521 was a randomized trial of radiotherapy (RT) and 24 months of androgen deprivation (ADT) with and without docetaxel (D) in high risk prostate cancer. We sought to evaluate whether post RT PSA was prognostic of outcomes and predictive of the benefit of D. We hypothesized that patients with a higher post RT PSA derive a benefit from D while those with a lower post RT PSA would derive no benefit. Methods: Patients treated on RTOG 0521 received 72-75.6 Gy in 40-42 fractions 8 weeks after starting ADT. In the experimental arm, D was started 28 days after RT. Per protocol, a PSA was to be drawn within 28 days after completion of RT (PRT-PSA). Hazard ratios (HRs) for PRT-PSA (>/≤ median level) were estimated by Cox proportional hazards regression for overall survival (OS) and Fine-Gray competing risks regression for prostate specific mortality (PCSM) and distant metastasis (DM), adjusting for baseline characteristics. As a sensitivity analysis for non-proportional hazards, HRs were estimated with follow up censored at 10 years. Results: PRT-PSA was available in 276/563 patients (114/281 in ADT alone and 162/282 in the ADT+D arm). PRT-PSA was drawn at a median of 15 days from the completion of RT and 120 days from randomization. 25% of patients had a PRT-PSA >0.1 ng/L. Patients with PSA >0.1 ng/mL had worse OS (HR 2.39, 95% confidence interval [CI] 1.51-3.79), PCSM (HR 3.78, 95% CI 1.87-7.62), and DM (HR 3.54, 95% CI 1.99-6.31) (all p<0.001). Baseline characteristics including Gleason score, T-stage, pretreatment PSA, performance status, and age were similar between patients with a PRT-PSA >0.1 and ≤ 0.1 ng/mL. In patients with PRT-PSA >0.1 ng/mL, there was no benefit seen with the addition of D to ADT alone in terms of OS (HR 1.06, p=0.88), PCSM (HR 0.97, p=0.96), or DM (HR 1.16, p=0.75). In patients with PRT-PSA ≤0.1 ng/mL, there was a benefit from the addition of D to ADT alone in terms of OS (HR 0.55, p=0.03) and PCSM (HR 0.36, p=0.02) but no significant benefit in terms of DM (HR 0.74, p=0.40). Results were similar in the sensitivity analysis for patients with PRT-PSA >0.1 ng/mL (OS HR 1.36, p=0.42; PCSM HR 1.71, p=0.39) and patients with PRT-PSA ≤0.1 ng/mL (OS HR 0.41, p=0.003; PCSM HR 0.26, p=0.006). Conclusions: PRT-PSA was prognostic of OS, DMFS, and DM in patients with high risk prostate cancer treated with RT and long term ADT +/- D. Despite having a worse prognosis, patients with PRT-PSA >0.1 ng/mL did not benefit from the addition of D while those with PRT-PSA ≤ 0.1 ng/mL had an OS and PCSM benefit from D. Clinical trial information: NCT00288080 . PRT-PSA (ng/mL) ADT, event/total ADT+D, event/total Adjusted HR (95% CI) Adjusted HR (95% CI)-10 y OS  ≤0.1 28/79 31/127 0.55 (0.32-0.95) 0.41 (0.23-0.73)  >0.1 21/35 18/35 1.06 (0.51-2.19) 1.36 (0.64-2.88) PCSM  ≤0.1 13/79 7/127 0.36 (0.15-0.87) 0.26 (0.10-0.67)  >0.1 15/35 11/35 0.97 (0.29-3.21) 1.71 (0.51-5.70) DM  ≤0.1 14/79 16/127 0.74 (0.37-1.50) 0.75 (0.37-1.50)  >0.1 16/35 16/35 1.16 (0.47-2.85) 1.09 (0.43-2.75)

Primary sarcomas of urinary bladder: A SEER analysis.

878 Background: Primary bladder sarcoma (PBS) is a rare entity. In this study, we analyzed demographics, clinical characteristics, and survival outcomes of PBS using the Surveillance, Epidemiology and End Results (SEER) database. Methods: We identified patients with urinary bladder sarcoma in the SEER database from the years 2000 to 2020 using the primary cancer site codes for urinary bladder as well as histological codes (ICD-O-3) that match the list of sarcoma histology found in the NCCN soft tissue sarcoma and bone cancer guidelines. Data for demographics, disease extent, median overall survival (OS), and treatment modalities were obtained. Sarcomas mixed with carcinomas, so-called carcinosarcomas, were included in the analysis. From the same database, OS data on urothelial carcinomas were obtained for comparison. Results: During the period of analysis, a total of 349,326 patients with primary bladder neoplasms were identified. Among them, 707 (0.002%) patients had PBS. The majority were Caucasian (71.9%) followed by Hispanics (12.9%) and African Americans (11.0%). There were 445 males (62.9%) with PBS. The most common histology was carcinosarcoma (40.9%), followed by leiomyosarcoma (20.4%), rhabdomyosarcoma (13%), and unspecified sarcoma (9.3%). Among the 654 patients with known extent of disease, 56.7%, 24.9%, and 18.3% had localized, locoregional, and distant metastatic disease, respectively. OS for patients with localized, regional, and distant diseases were 32, 12, and 4 months, respectively (P<0.0001). Bladder sarcomas were associated with worse survival than urothelial carcinomas (14 months vs. 92 months, P<0.01). OS was longer in patients with pure sarcomas compared to patients with mixed sarcomas (26 months vs. 9 months, P< 0.001). Among the 697 patients with treatment data available, 34 (4.9%) received chemotherapy only, 468 (67.1%) received surgical resection only, 152 (21.8%) received both, and 43 (6.2%) received neither. Both chemotherapy and surgery were associated with longer median OS. Those who received chemotherapy showed a median OS of 42 months compared to 9 months seen in the no chemotherapy group (P<0.001). As for surgical resection, median OS of those who underwent surgery was 16 months compared to 8 months in those who did not (P=0.014). Conclusions: Bladder sarcomas are rare and associated with worse outcomes when compared to urothelial carcinoma. Carcinosarcomas are associated with worse survival when compared with pure sarcomas. More than half of the bladder sarcomas were diagnosed as localized disease and survival was better when compared with locoregional or distant disease. Chemotherapy and surgical resection were associated with longer median OS, but prospective studies are needed to ascertain these findings after controlling for confounders.

Mortality risk in clinical T1a renal cell carcinoma (RCC) with synchronous metastasis (SM): A comparative analysis of National Cancer Database (NCDB).

513 Background: The incidence of RCC has been rising, largely due to increased incidental detection from widespread imaging. Although SM with a primary renal tumor measuring <4 cm (cT1a) is uncommon, its presence may influence survival outcomes and utility of cytoreductive nephrectomy. We sought to examine trends, metastatic patterns, treatments and survival outcomes of cT1a RCC with SM. Methods: All cases of RCC (age ≥ 18 years), diagnosed between 2004-2019, were extracted from the NCDB. The Cochran-Armitage test was utilized for trend analyses. Multivariable analyses were conducted to compare variables associated with all-cause mortality across metastatic sites. Results: Overall, 263,911 patients with T1a RCC were included in the analysis. Of these, 114,661 patients (43.4%) had cT1a tumor stage and within this group, 2,275 (2.0%) presented with SM. From 2004-2019, the proportion of SM cT1a decreased from 3.39% to 2.08% (AAPC=-0.037%; Cochran-Armitage p=0.830). The median follow-up was 8.8 months. The most common site of metastasis was bone (59%), followed by lung (35%), liver (16%), and brain (12%). Among SM cT1a patients, 11% underwent radical nephrectomy, 4.7% partial nephrectomy, 15.4% metastasectomy, and 45.2% received systemic therapy. Variables associated with all-cause mortality demonstrated in the table. Conclusions: Uniquely, bone was the most common metastatic site in cT1a RCC with synchronous metastasis, contrasting with the typical lung predominance in larger tumors. Primary tumor resection and receipt of systemic therapy showed potential survival benefits in patients with isolated metastases, while metastasectomy improved survival in brain-only metastases but not in bone-, lung-, or liver-only metastases.These findings highlight the heterogeneous nature of tumor biology in small renal masses and underscore the importance of tailored, multimodal treatment strategies for effective management of cT1a RCC with SM. Multivariable Cox regression models demonstrating variables associated with all-cause mortality in cT1a RCC with SM to lung, bone, liver, and brain. SM to Lung SM to Bone SM to Liver SM to Brain Variables HR (95% CI) p-value HR (95% CI) p-value HR (95% CI) p-value HR (95% CI) p-value Age 0.98 (0.96-1.01) 0.178 1.03 (1.02-1.04) <0.001 1(0.97- 1.03) 0.989 0.99(0.96- 1.03) 0.748 Surgery of Primary Site Nephrectomy 0.08(0.01- 0.72) 0.047 0.35(0.14- 0.86) 0.056 0.22(0.06-0.78) 0.039 0.08(0.02- 0.41) 0.005 Partial Nephrectomy 0.02(0.00- 0.31) 0.013 0.23(0.09- 0.60) 0.011 0.13(0.01- 2.35) 0.165 0.1(0.01- 0.97) 0.047 Metastasectomy 0.91(0.50- 1.67) 0.759 0.81(0.59- 1.10) 0.169 3.14(0.90- 11.0) 0.074 0.26(0.10- 0.68) 0.006 Systemic Therapy 0.36(0.23-0.57) <0.001 0.57(0.44- 0.74) <0.001 0.41(0.20- 0.85) 0.033 0.22(0.10- 0.48) <0.001 HR = hazard ratio, CI = confidence interval.

Treatment patterns and clinical outcomes in patients with metastatic urothelial carcinoma in England: A retrospective observational study.

740 Background: In England, platinum-based chemotherapy with or without an immune checkpoint inhibitor is the standard-of-care for mUC patients. However, treatment patterns following first-line therapy remain unclear. There is a need to collect real-world data to enable an improved understanding of the clinical management of mUC in the National Health Service (NHS) and associated outcomes. Methods: This retrospective study obtained routine data for all patients diagnosed with mUC in England between January 2016 and December 2021 from the National Cancer Registration and Analysis Service (NCRAS). A treatment-based algorithm was developed to approximate progression to metastatic disease for those patients who had non-metastatic UC (Stage I-III). Variables collected include patient demographics, tumour characteristics, diagnostic tests, comorbidities, healthcare resource use, systemic anti-cancer therapy (SACT) and distributions of patients by lines of treatment. Kaplan-Meier methods were used to calculate overall survival (OS). Results: Of 61,816 patients diagnosed with UC between 2016 and 2021, 10,787 patients had mUC (stage IV (79.7%) at diagnosis or stage I-III (20.3%). The median age at diagnosis was 73.9 years, with 66.0% being male. Patients treated with anti-PD-L1 had a median age of 68.8 years. Only 36.5% (n = 3,942) received first-line therapy, with 24.3% (n = 959) reaching second-line therapy, while third-line therapy was delivered to 4.0% (n = 158) and fourth-line therapy to just 0.5% (n = 19) of patients with derived lines of therapy. The most common first-line regimen was ‘carboplatin + gemcitabine’ (n = 1,497; 38.0%), followed by ‘cisplatin + gemcitabine’ (n = 1,153; 29.2%). Pembrolizumab was the most common regimen administered at second line (n = 284; 29.6%) and remained the most common regimen at third line (n = 52; 32.9%). For the entire cohort, including patients that did not receive an active treatment, 12-month survival probability was 29.0%. The survival probabilities for patients treated at first-line, and reaching second-line and third-line, were 45.0%, 34.0%, and 30.0%, respectively. For the entire cohort, including patients that did not receive an active treatment, 12-month survival probability was 29.0%. The survival probabilities for patients treated at first-line, and reaching second-line and third-line, were 45.0%, 34.0%, and 30.0%, respectively. Conclusions: A high attrition rate in SACT was observed in mUC patients, and a poor prognosis indicated by a median OS of only 5.4 months from diagnosis. New treatment options particularly in the second-line setting could improve outcomes for patients. Further real-world studies are needed to evaluate their impact within routine clinical practice.

Differences in sensory nerve block between levobupivacaine and bupivacaine at low concentrations in humans and animals

Physiochemical properties of levobupivacaine and bupivacaine are identical, but pharmacokinetic and pharmacodynamics properties differ due to stereoselective interactions at the molecular sites of action. An evaluation of nerve block characteristics is essential for optimal clinical application. This study compared the sensory blocking characteristics of levobupivacaine to bupivacaine in humans and model animals. Levobupivacaine and bupivacaine were compared for sensory block efficacy using a randomized, double-blinded, crossover study design. Eighteen healthy volunteers were randomized to receive levobupivacaine or bupivacaine by subcutaneous injection into the forearm, followed by the other drug 1 week later with injection order counterbalanced across subjects. Tactile detection and mechanical pain thresholds were determined using von Frey hairs and thermal pain threshold using a thermal stimulator. Effects of levobupivacaine and bupivacaine, on the spiking activity of spinal dorsal horn (SDH) neurons evoked by innocuous or noxious stimuli were also compared in anesthetized Sprague–Dawley rats by in vivo extracellular recordings. There were no significant differences in mechanical and thermal pain thresholds following levobupivacaine or bupivacaine injection at 0.025%, 0.0625%, and 0.125%. There was also no significant difference in tactile detection threshold following levobupivacaine or bupivacaine injection at 0.125%. However, tactile detection threshold was significantly higher after administration of bupivacaine at 0.025% and 0.0625% compared to equivalent doses of levobupivacaine. Subcutaneous injection of bupivacaine at 0.05% also induced significantly greater inhibition of SDH neuron spiking activity evoked by innocuous stimuli compared to an equivalent dose of levobupivacaine, while there was no significant difference in suppression of spiking activity evoked by noxious stimuli. Low-dose bupivacaine induces greater suppression tactile sensation than low-dose levobupivacaine. Thus, low-dose levobupivacaine demonstrates relatively greater blocking selectivity for noxious over innocuous stimuli compared to low-dose bupivacaine. Levobupivacaine may be advantageous for applications where pain must be suppressed but non-nociceptive sensations maintained.

Disaster victim identification: the co-utilisation of applied biosystems RapidHIT ID system and DJI Matrice 300 drone for onsite DNA analysis

Automated classification of treatment state of patients with prostate cancer from structured medical record data to help enhance care.

427 Background: The number of US prostate cancer (PCa) cases is projected to expand exponentially while the oncology workforce stagnates. The increase in clinic demand requires innovative technologic approaches for patient management. We are developing a process for automatically tracking patients across the care continuum which can flag patients overdue for follow-up, send alerts when patients recur, and thereby optimize clinic resources. In order to place patients into the correct care pathway, their disease status must be correctly classified, which is the focus of the current study. Methods: Clinician specialist input was used to define five mutually exclusive care states in PCa (newly diagnosed, active surveillance, active treatment, post-treatment surveillance, and metastatic). Using a variable set defined to classify each care state, decision tree modeling was applied to abstracted, de-identified data from 150 patients seen in the Dana-Farber/Brigham Cancer Center radiation oncology clinic between 5/14 and 8/14/2024 to validate model care state classification. Model output and a case summarization were presented in an interactive web-interface designed using user experience principles. Through a secure login, a provider accessed the data for each case and recorded if the care state assignment and case summary were accurate. Results: The concordance between the model classification and provider assignment was 100%. The model correctly sorted the care states of each of the patients, of which the distribution was 0% newly diagnosed, 1% active surveillance, 12% active treatment, 73% post-treatment surveillance, and 13% metastatic The interactive web interface included graphical and table views of PSA test values with automatic calculation of doubling time and velocity. In addition, treatment events (prostatectomy, radiation, hormone therapy) were overlaid on the PSA graph for easy clinical analysis. A treatment summary table provided a chronologic view for each patient. Conclusions: The care state assignment model was able to correctly classify the care state of all 150 patients in this cohort for which structured, provider abstracted data was available. The next steps in clinical implementation will be EMR integration, automatic record abstraction, and end-user testing. We have already begun work to automatically ingest and parse PCa records using natural language processing and expand the user interface to include a patient care journey map, generation of a pre-visit clinical note, and care optimization protocols. The goal is to provide a tool that will decrease time for case review and appointment preparation, give case prioritization alerts based on PSA testing results, and automatically monitor surveillance care compliance thus optimizing clinic resources while ensuring no patient is lost to follow-up.

A high omega-3, low omega-6 diet with fish oil for men with prostate cancer on active surveillance: The CAPFISH-3 randomized clinical trial.

312 Background: Men on active surveillance for prostate cancer are extremely interested in dietary changes or supplements to prevent progression of their disease. There are presently no prospective trials supporting such changes. We sought to determine if a high omega-3, low omega-6 fatty acid diet with fish oil capsules (D+FO) decreases proliferation (Ki-67) in prostate biopsies in men with prostate cancer on active surveillance over a 1-year time period. Methods: In this Phase II, prospective randomized trial, men (N=100) with grade group 1 or 2 prostate cancer that elected active surveillance were randomized to the D+FO or a control group. Same site prostate biopsies were obtained at baseline and 1-year tracked using an image-fusion device. The primary endpoint was the change in Ki-67 index from baseline to 1-year from same site biopsies compared between the groups. Ki-67 index was determined using multiplex immunofluorescence analysis. Secondary outcomes included compliance, grade group, maximum tumor length, the Decipher 22 gene score, serum PSA, lipid levels, and adverse events. Results: The Ki-67 index decreased in the D+FO group by approximately 15% from baseline to 1-year (1.34% at baseline, 1.14% at 1-year) and increased in the control group by approximately 24% from baseline to 1-year (1.23% at baseline, 1.52% at 1-year) resulting in a statistically significant difference in the change of Ki-67 index between the groups (95% CI 2%, 52%, p=0.043). There was no significant difference in the secondary outcomes grade group, tumor length, decipher genomic score or PSA between the two groups. There was a significant decrease in serum triglyceride (p=0.016) and serum colony stimulating factor-1 (p=0.017) in the D+FO group compared to control. Four patients in the D+FO group were withdrawn from the trial due to adverse events related to the FO. Conclusions: A high omega-3, low omega-6 diet with FO for 1-year resulted in a significant reduction in Ki-67 index (compared to the control group), a biomarker for prostate cancer progression, metastasis and death. These findings support future Phase III trials incorporating this intervention in men on active surveillance. Clinical trial information: NCT02176902 .

Ethnic disparities in clinical trials for FDA-approved drugs in urothelial cancer: An analysis in the post-COVID-19 era (2020-2024).

677 Background: Ethnic and racial disparities in oncology clinical trial participation continue to pose significant challenges. Despite initiatives by the NCI and FDA to address these disparities through policies established in 2017, notable gaps in both cancer treatment and clinical trial involvement persist. There is a lack of comprehensive data regarding minority participation in clinical trials for FDA-approved urothelial cancer therapies in the post-COVID-19 context. Methods: From 2020 to 2024, we examined data from 2,755 patients recruited in eight industry-sponsored clinical trials (BCL2001, CheckMate 274, CheckMate 901, EV-302, KEYNOTE 057, CS-003, QUILT-3.032, TROPHY) that led to the FDA approval of new agents or indications for urothelial cancer. We assessed and tabulated the reporting of racial demographics within these trials, employing chi-square statistics and machine learning algorithms to compare participation among White, Black, Asia and Hispanic patients against SEER data on urothelial cancer incidence. Results: Race data was reported in 7 (BCL2001, CheckMate 274, CheckMate 901, EV-302, CS-003, QUILT-3.032, TROPHY) out of 8 trials (87.5%), but only 5 (CheckMate 274, CheckMate 901, EV-302, CS-003, TROPHY) of these trials (71%) included data on Black and Asian populations alongside White participants. Notably, none of the trials reported date on Hispanic participants. Our analysis revealed that in the 7 trials providing race data, 79% of participants were White, indicating overrepresentation (p=0.013). among the 5 trials with comprehensive race reporting, Blacks were unrepresented at 2.3% (p=0.001), while Asians constituted 10%, showing no statistical significance (p=0.90) in difference in representation. No data was available for Hispanics. Conclusions: The continued underrepresentation of minorities in FDA-approved clinical trials for urothelial cancer is a pressing concern still in the post-COVID-19-era. To rectify these issues, it is essential to implement policies that improve data collection and standardize ethnic nomenclature. Furthermore, international collaborative trials should prioritize separate data reporting for U.S. participants, utilizing NCI SEER nomenclature to endure accurate representation and analysis.

Associations between protein biomarkers and adverse pathologic features in MRI-mapped prostate cancers: An interim analysis.

405 Background: While standard mpMRI has shown benefit in increasing detection of clinically significant prostate cancer, it is limited in its ability to detect small lesions, low Gleason scores, and certain tumor architectures. Proteomics may supplement imaging and enhance prediction of clinical outcomes. We investigated associations between MRI-mapped tumors and protein levels obtained from radical prostatectomy (RP) specimens and correlated them to adverse pathology features. Methods: This was an interim analysis of a planned cohort of 124 subjects. Patients underwent routine preoperative mpMRI and whole-mount histopathology after RP, with proteomic analysis performed on tissue from MRI-mapped tumors. A panel previously shown to improve prediction of distant metastasis in RP patients included five proteins: TGFβ-1, SPARC, FOLH1 (PSMA), CAMKK2, and tumor PSA. Protein concentrations were log transformed. Logistic regression assessed protein associations with adverse pathologic features, including extracapsular extension (ECE), seminal vesicle invasion (SVI), lymph node invasion (LNI), Gleason score ≥8, and a composite of these findings. Multivariate analyses were adjusted by patient age, PSA, Gleason Grade Group, and T stage at diagnosis. Results: 61 patients had proteomic data; mean age at diagnosis was 64 years and mean PSA at diagnosis 10 ng/dL. ECE was present in 67%, SVI 20%, LNI 21%, and Gleason score ≥8 26%; 72% had at least one adverse pathologic feature. On initial multivariate analysis of proteins alone, TGFβ-1 significantly correlated with LNI (odds ratio [OR] 24.4 [95% confidence interval (CI) 3.7-160.2], p = 0.0009) and composite adverse pathology (OR 3.1 [95% CI 1.0-9.3], p = 0.05). Even after including clinical characteristics in the model, TGFβ-1 still significantly correlated with LNI (Table). None of the other proteins significantly correlated to these markers of adverse pathology. Conclusions: In this study assessing protein associations with MRI-identified prostate tumors, TGFβ-1 was strongly predictive for LNI. TGFβ signaling has been associated with both prostate cancer suppression and promotion depending on context. Further investigation will assess if the combination of proteins in the panel is more predictive of adverse pathology. Multivariate logistic regression analyzing association between proteins and lymph node invasion. Protein Odds ratio (95% CI) p-value TGFβ-1 235.0 (4.5-N/A) 0.007* SPARC 1.4 (0.3-7.3) 0.7 FOLH1 0.8 (0.3-2.4) 0.7 CAMKK2 2.0 (0.7-5.8) 0.2 PSA 2.0 (0.7-5.6) 0.2 Protein concentrations were log transformed and models included patient age, PSA, Gleason Grade Group, and clinical T-stage at diagnosis.

Genome wide association study reveals novel associations with face morphology

Genome-wide association studies (GWAS) on the Middle Eastern population, including the United Arab Emirates (UAE), have been relatively limited. The present study aims to investigate genotype-face morphology associations in the UAE population through Genome Wide Association Studies (GWAS). Phenotypic data (44 face measurements) from 172 Emiratis was obtained through three-dimensional (3D) scanning technology and an automatic face landmarking technique. GWAS analysis revealed associations of 19 genetic loci with six face features, 14 of which are novel. The GWAS analysis revealed 11 significant relationships between 44 face parameters and 242 SNPs, exceeding the GWAS significance threshold. These phenotypes were previously associated with body height, craniofacial defects, and facial characters. The most significant associations of these genetic variations were related to six main facial features which were facial convexity, left orbital protrusion, mandibular contour, nasolabial angle D, inferior facial angle B, and inferior facial angle A. To the best of our knowledge, this is the first GWAS study to investigate the association of SNP variations with face morphology in the Middle Eastern population.

Biopsychosocial based machine learning models predict patient improvement after total knee arthroplasty