Citations

Background: Solid organ transplant (SOT) recipients are living longer and, consequently, more of them require elective total hip arthroplasty (THA) to restore mobility and improve quality of life. Because these patients are chronically immunosuppressed and often burdened by multiple comorbidities, their peri-operative risk profile may differ substantially from that of the general THA population. This study aimed to evaluate risk factors associated with acute medical and surgical complications, implant survivorship, and overall mortality in patients with a history of SOT who underwent THA. Methods: A total of 173 THA procedures were reviewed in patients with previous SOT. Among them, 64 had undergone liver transplantation (LT), 83 had received renal transplants (RT), and 26 had experienced more than one type of organ transplant (MT). Kaplan–Meier survival analysis was employed to estimate median survival. Complications were examined using univariate analysis through mixed-effects logistic regression, while Cox regression was utilized to assess mortality risk. The median follow-up period extended to 99 months. Results: The proportion of patients experiencing at least one acute medical event was 27% in the LT group, 33% in the RT group, and 38% in the MT group, with no statistically significant difference between groups (p = 0.5). American Society of Anesthesiologists Class (ASA) 4 (Odds Ratio (OR) = 28; p = 0.006) and treatment with bisphosphonates (OR = 2.25; p = 0.03) were associated with higher risk of acute medical complications. Increased age at the time of SOT was linked to a reduced likelihood of surgical complications (OR = 0.94, p = 0.008), as was older age at the time of undergoing THA (OR = 0.92, p = 0.001). The observed rates of reoperation and implant revision were 3% and 1%, respectively. The estimated patient survivorship rates at 1, 5, and 10 years were 98.6, 82, and 58.4%, respectively. Older age at SOT (Hazard Ratio (HR) = 1.06, p < 0.001), at THA (HR = 1.08, p < 0.001), ASA 4 at THA (HR = 7.57, p = 0.02), and atrial fibrillation (AFib) (HR = 3.13, p = 0.02) were associated with higher mortality. Conclusions: ASA 4 and bisphosphonates were associated with a higher risk of acute medical complications, whereas older age was associated with lower surgical complications. Additionally, older age, ASA 4, and AFib were associated with higher mortality.

ABSTRACTBackgroundThe treatment landscape for multiple myeloma continues to evolve. Recently, the addition of anti‐CD38 monoclonal antibodies (mAbs) to the triplet regimen, comprising a proteasome inhibitor, an immunomodulatory agent, and a steroid, for transplant‐eligible newly diagnosed multiple myeloma (TENDMM) has shown promising results.AimsTo evaluate the overall efficacy and safety of quadruplet therapy with an anti‐CD38 mAb compared to a triplet regimen.MethodsA systematic search of Medline, Scopus, and EMBASE databases from inception to July 2024 identified relevant randomized controlled trials (RCTs). Efficacy and safety outcomes were derived using random‐effects meta‐analysis. Summarized outcomes include hazard ratios (HR) for progression‐free survival (PFS) and overall survival (OS), odds ratios (OR) for response rates, measurable residual disease (MRD) negativity rate, and grade 3 or higher adverse events (G ≥ 3 AEs).ResultsFive RCTs involving 2963 patients were included. A statistically significant PFS was observed for quadruplet therapy when compared to the triplet regimen (HR 0.44; 95% Confidence Interval [CI] 0.35–0.56). PFS benefit was consistent for the standard risk (SR) group (HR 0.38; 95% CI 0.27–0.52) and high risk (HiR) group (HR 0.62; 95% CI 0.41–0.92). No statistically significant benefit was observed for OS (HR 0.55; 95% CI 0.28–1.08). A statistically significant benefit was observed for the overall response rate (OR 1.77; 95% CI 1.02–3.06) and MRD negativity rate (OR 2.67; 95% CI 1.79–3.99). No significant differences were observed for G ≥ 3 AE (OR 1.21; 95% CI 0.92–1.58), lymphopenia (OR 1.09; 95% CI 0.62–1.89), and anemia (OR 1.06; 95% CI 0.83–1.37). However, a significantly increased risk was observed for all‐grade thrombocytopenia (OR 1.64; 95% CI 1.37–1.97), neutropenia (OR 2.24; 95% CI 1.67–3.02) and infections (OR 1.88; 95% CI 1.07–3.31).ConclusionQuadruplet therapy demonstrated a favorable efficacy and safety profile, with consistent benefit across subgroups. The findings support its potential as the new standard of care for TENDMM.

Kidney transplantation remains the gold standard for managing end-stage kidney disease, providing superior survival and quality-of-life outcomes compared to dialysis. Despite the ongoing gap between organ availability and demand, it is inevitable that kidney transplantation will continue to grow. This is owed to broader organ sharing, increased comfort of transplant programs with marginal kidney utilization, and the expansion of paired exchange among living donor kidneys. The evolution of kidney transplantation could not have been possible without the availability of effective immunosuppressive regimens that prevent rejection and maintain graft function. Mycophenolic acid and calcineurin inhibitors continue to serve as the foundation of modern maintenance immunosuppression. While these agents have markedly reduced acute rejection rates, their long-term efficacy in graft survival remains suboptimal. Alternative immunosuppressive therapies, including belatacept and mammalian target of rapamycin inhibitors, have demonstrated potential benefits. However, concerns regarding an increased risk of rejection have limited their widespread adoption as primary treatment options. In addition to ongoing efforts to refine steroid- and calcineurin inhibitor-sparing strategies, the identification of practical and quantifiable biomarkers for predicting long-term graft survival remains a critical objective. This review evaluates contemporary immunosuppressive protocols, highlights existing challenges, and explores future directions for optimizing long-term transplant outcomes.

261 Background: Clinicians use next-generation sequencing (NGS) to tailor targeted treatments for PCa patients. However, the results are often available in unstructured formats and are saturated with technical jargon, making them inaccessible for patients. Therefore, we aimed to assess the efficacy of LLMs to accurately extract genomic characteristics from unstructured reports and generate patient-friendly summaries for ease of variant interpretation in PCa patients. Methods: This retrospective study included patients with PCa who underwent NGS from 2023-2024. The GPT4 model was utilized using structured zero-shot prompts to extract genomic characteristics from unstructured reports in a non-decomposed manner. Prompt development was conducted iteratively using a 2% random sample of the dataset. Genomic characteristics ascertained by LLM were assessed against held out vendor-curated test dataset for evaluation. Performance was assessed using weighted evaluation metrics (precision, recall, and F1-score). Additionally, the extracted variables were organized using rule-based criterion and presented as a separate prompt to GPT4 to generate summaries for interpretation at the level of each biologically relevant variant. Mean Flesch-Kincaid scores and Vocd-D statistic with standard deviations were computed to assess readability and lexical diversity of LLM-generated variant interpretation summaries. Results: A total of 331 patients (370 NGS reports) were included in the study. Evaluation on the held-out test dataset (Table) showed that the weighted average precision ranged from 80% for extracting tumor mutational burden to 100% for extracting the CtDNA fraction from unstructured reports. The weighted average recall ranged from 85% for extracting CtDNA tumor fraction to 99% for ascertaining variant/alteration. The weighted average F1-scores varied from 0.83 for extracting tumor mutational burden to 1.0 for extracting specimen site from NGS reports. The mean Flesch-Kincaid score was 8.29 ± 1 indicating average/standard readability ease. The mean Vocd-D statistic was 7.55 ± 1 indicating focused summaries, however, with limited lexical diversity. Conclusions: This study suggests that large language models can effectively extract genomic characteristics from unstructured reports and can potentially improve genomic literacy among prostate cancer patients by providing easy-to-interpret variant summaries. However, targeted prompting may be required to increase lexical diversity for improved engagement. Performance across different genomic characteristics. Category Precision Recall F1-Score Altered gene 0.86 0.97 0.89 Variant/alteration type 0.98 0.99 0.98 Variant allele fraction 0.96 0.96 0.96 Test name/type 1 0.99 1 Specimen site 1 0.99 1 Tumor mutational burden 0.8 0.93 0.83 CtDNA tumor fraction 1 0.85 0.92 MSI status 0.99 0.97 0.98

270 Background: Inconsistent reporting of subgroup data across clinical trials makes interpretation and application of the evidence from trials challenging. We conducted a living systematic review to summarize evidence for American Society of Clinical Oncology (ASCO) guidelines for management of metastatic castration resistant prostate cancer (mCRPC). Here, we provide an overview of reporting patterns of subgroup data across mCRPC trials. Methods: MEDLINE and EMBASE were systematically searched from each database's inception through September 20 th , 2024, to identify phase II/III/IV randomized clinical trials assessing the efficacy and safety of treatment options in mCRPC. For outcomes of overall survival (OS) and progression free survival (PFS), data from the subgroup analyses was collected and compared across trials to assess heterogeneity in the reporting of subgroups. Results: This analysis included 141 trials (phase II: 83; phase III: 56; phase IV: 2). OS was reported by 113 (80%) trials; 32 (28%) reported OS by any subgroups with 95 unique subgroup categories. PFS was reported by 110 (78%) trials; 23 (21%) reported PFS by any subgroups with 63 unique subgroup categories. Even among consistently reported subgroups, such as age, ECOG performance status, race, geographical area, and Gleason score, considerable heterogeneity in different subgroup levels/thresholds was observed across trials. Top ten most commonly reported subgroups are summarized (Table). Conclusions: Lack of consistent reporting for subgroup analysis in mCRPC trials preclude meaningful conclusions about clinically relevant subgroup and synthesizing evidence for clinical guidelines. A standardized framework for consistent reporting of subgroup data across trials can help inform clinical practice and clinical practice guidelines. OS PFS Number of trials 113 110 Reporting subgroup analysis – N (%) 32 (28) 23 (21) Commonly reported subgroups – (N) Age (26)ECOG-PS (26)LDH (21)PSA (18)Geographic area (15)Alkaline phosphatase (14)Visceral disease (14)Gleason score (9)Race (9)Brief pain inventory level (8) Age (21) ECOG-PS (19)PSA (18)LDH (14)Geographic area (13)Visceral disease (11)Gleason score (10)Alkaline phosphatase (9)Bone metastasis (9)Disease location (9) Age – (N) <65 (14); ≥65 (9); ≤68 (1); ≥69 (1); <70 (5); ≥70 (5); ≤74 (4); 65-75 (5); ≤ 71 (1); >71 (1); ≥75 (11); >Median (1); <Median (1) <65 (12); 65-74 (6); ≥65 (6); <70 (5); ≥70 (5); <75 (4); ≥75 (10); 76-80 (1); >80 (1) ECOG-PS – (N) 0 (15); 0-1 (11), 1 (11); 1-2 (5); 2 (12) 0 (15); 0-1 (5), 1 (12); 1-2 (2); 2 (6) Race – (N) White (9)Non-white (6)African American/black (2)Asian (2) White (8)Non-white (5)African American/black (2)Asian (4) Geographic Area – (N) Europe (8)North America (14)United States (1)Australia (1)Asia (2) Europe (11)North America (13)United States (1)Australia (1)Asia (2)North and South America (2) Gleason Score – (N) 2-6 (1); 7 (1); 8 (1); <8 (8); ≥ 8 (8); 9-10 (1) <8 (10); ≥ 8 (10)

520 Background: The annual incidence of renal cancer is 0.02% among the general United States population. End stage renal disease (ESRD) and exposure to dialysis are thought to be the primary drivers of increased risk of renal cancer in renal transplant patients rather than immunosuppression. This has been evidenced by how the incidence of RCC in heart transplant recipients is no different than the normal population. In this study, we aim to characterize RCC incidence among kidney transplant patients (usually exposed to ESRD/dialysis) versus other solid organ transplant patients (usually unexposed to ESRD/dialysis). Methods: We used CPT codes to search for patients who had received a solid organ transplant (kidney, liver, heart, lung, pancreas) at all Mayo Clinic sites from 1/1/2018 to 1/1/2024. Within this cohort, we identified those who had been diagnosed with kidney cancer after initiating dialysis or receiving a transplant, and retrospectively extracted data related to demographics, cancer diagnosis, and transplant details. Results: We identified 10873 patients who had received a solid organ transplant (Table 1). Of these, 178 (1.76%) were diagnosed with kidney cancer after either starting dialysis or receiving a transplant. These 178 patients were of median age 56 years at time of cancer diagnosis (STD 12), 71% male, 70% white, 20% black, 4.5% Asian, 2.8% American Native. Of 5792 patients who had received a kidney transplant (with or without another solid organ transplant), 172 (2.97%) were diagnosed with kidney cancer after having started dialysis or receiving a kidney transplant. Of these 172, 156 (91%) were exposed to dialysis (107 primarily hemodialysis and 48 peritoneal). Of 4392 patients who had received a solid organ transplant other than kidney (liver, heart, lung, and/or pancreas), 6 (0.14%) were diagnosed with kidney cancer after having received a kidney transplant. Of these 6, none underwent dialysis. Conclusions: Patients with kidney transplants are at increased risk of kidney cancer compared to patients with non-kidney solid organ transplants (2.97% vs 0.14%). This supports prior evidence showing ESRD plays a significant role in the pathogenesis of kidney cancer. Patients who received solid organ transplants at Mayo Clinic from 2018-2024 and were subsequently diagnosed with kidney cancer. n % With RCC after TXP 178 1.7587% Cancer Diagnosis after Kidney HD/TXP 172 2.9696% Cancer Diagnosis after Other TXP 6 0.1386% Patients who received solid organ transplants at Mayo Clinic from 2018-2024 n % Unique Patients 10121 100% Kidney Transplant 5792 57.23% Alone 5088 50.27% &Liver 332 3.28% &Heart 119 1.18% &Lung 8 0.08% &Pancreas 245 2.42% Non-kidney Transplant (Liver, Heart, Lung, or Pancreas) 4329 42.77% TXP: Transplant, HD: Hemodialysis.

745 Background: The combination of EV-P therapy has recently been approved as first-line (1L) therapy for patients with LA/mUC based on the results of the EV-302 trial. Herein, we report the updated results from a cohort of patients with LA/mUC who received EV-P in real world clinical setting. Methods: This retrospective study included patients with LA/mUC (07/2022-08/2024) at the Mayo Clinic who completed at least one cycle of EV-P. The best overall response (BOR) was evaluated using radiographic imaging and was adjudicated as complete response (CR), partial response (PR), stable disease (SD), mixed response (MR), or progressive disease (PD). The median progression-free survival (PFS), defined as the time from treatment initiation to disease progression or death, was estimated using the Kaplan-Meier method. Patients who had not experienced disease progression by their last follow-up were censored for the PFS analysis. Results: A total of 120 patients were included; 79 (65.8%) were males, 41 (34.1%) females, 109 (91%) White, and 119 (99%) were non-Hispanic/Latino. The median age was 72 years (IQR: 65-77). Of these, only 22 (18.3%) had locally advanced disease while the remaining had mUC; 62 (51.6%) had lower tract urothelial carcinoma (LUTC), 36 (30%) had upper tract urothelial carcinoma (UTUC). The median follow-up time was 7.1 months (IQR: 4.93-9.26). In terms of BOR, 56 patients (46.6%) experienced PR, 34 (28.3%) CR, 12 (10%) PD, 7 (5.8%) MR, and 8 (6.6%) experienced SD. 3 (2.5%) patients were not evaluable. The BOR across subgroups, LA and mUC, including LUTC and UTUC, is summarized in the table. Among the responders, the median number of treatment cycles to first response was 3 (IQR: 2.25–4). Within the follow-up, 28 patients (23.3%) experienced eventual radiographic disease progression; death was observed in 25 patients (20.8%). The median PFS was 12.7 months (95% CI: 9.8-NE), and OS was 25.1 months (16.3-NE). Conclusions: In real world setting, the combination of EV-P in LA/mUC demonstrated clinical efficacy compatible with the findings from the EV-302 trial. Our results showed comparable efficacy with EV-P in both UTUC and LUTC, highlighting it's broad therapeutic potential. However, clinical data at longer follow-up is required to fully evaluate overall survival and the durability of response. mUC LA Overall LUTC UTUC Total patients 98 62 36 22 BOR CR 23 (23.4%) 13 (20.9%) 10 (28.5%) 11 (50%) PR 49 (52.6%) 31 (50%) 18 (50%) 7 (31.8%) SD 6 (6.4%) 2 (3.2%) 4 (11.4%) 2 (9.0%) PD 10 (10.7%) 9 (15.5%) 1 (2.8%) 2 (9.0%) MR 7 (7.5%) 5 (8.6%) 2 (5.7%) 0 (0%)

134 Background: Prostate cancer patients with visceral metastases at diagnosis are often treated using one-size-fits-all approach. For example, CHAARTED criteria treats any visceral metastasis as high volume. Therefore, we aimed to assess overall survival (OS) by site of visceral involvement in patients with metastatic PCa. Methods: Surveillance, Epidemiology, and End Results (SEER) database (2010-2021) was queried to obtain case listing data on metastatic PCa patients from 17 registries. The patients were categorized into three groups based on visceral metastasis at diagnosis: lung metastasis, liver metastasis, and others. Kaplan-Meier survival analysis was performed to estimate median OS with 95% confidence interval (CI). Log-rank test was conducted to assess if survival was significantly different among the groups. Cox proportional hazard regression analysis was performed to assess the magnitude of difference among the groups. P-value <0.05 established statistical significance. Results: This analysis included 21,007 metastatic PCa patients (lung: n=319; liver: n=123; brain: 107; bone: 20538). Metastatic PCa population with lung metastasis exhibited a median OS of 60 months (95% CI: 48-72) compared to 24 months (95% CI: 12-36) in population with liver metastases and to 36 months (95% CI: 36-36) in population with other metastases. The difference in OS among the groups was statistically significant (p < 0.001). Compared to population with lung metastasis, those with liver (HR: 1.91; 95% CI: 1.41-2.57) but not those with other metastases (1.16; 0.97-1.39) had significantly worse OS adjusting for Gleason score, PSA and race (Table). Conclusions: In metastatic PCa, patients with lung-only metastasis have significantly better overall survival and should be considered differently in prognostication to liver metastases. Consideration of site of visceral metastasis is critical for treatment intensification decisions. Limitations of this analysis include lack of accounting for confounding relationships at individual patient level. Variable Hazard Ratio (95% CI) Metastases (Lung) REFERENCE Metastases (Liver) 1.91 (1.41-2.57) Metastases (Other) 1.16 (0.97-1.39) Gleason score≥8 REFERENCE Gleason score <8 0.68 (0.64 -0.72) PSA - ng/dL 1.01 (1.00 – 1.01) Race (White) REFERENCE Race (Black) 0.99 (0.94 – 1.05) Race (Asian or Pacific Islander) 0.70 (0.64 – 0.76)

132 Background: Distant metastasis at the time of prostate cancer (PCa) diagnosis is associated with increased morbidity and mortality. This study aimed to assess the impact of sociodemographic characteristics on distant metastasis at the time of PCa diagnosis. Methods: The Surveillance Epidemiology and End Results (SEER) database (2000-2021), including PCa patients from 17 registries, was queried. Patients with late-stage diagnosis (LSD) were defined as those who were initially diagnosed with stage IV disease, indicating distant metastasis. Sociodemographic predictors included race, ethnicity, age, marital status, residential status, and median household income. Multicollinearity was assessed using variance inflation factors (VIF). Univariable logistic regression was performed to identify significant predictors of LSD, which were further analyzed in multivariable logistic regression using a maximum likelihood estimation approach. Odds ratios with 95% confidence intervals (CI) were computed with a p-value of <0.05 indicating a statistically significant association. Results: Of the 1,089,736 PCa patients diagnosed, 64,983 (6%) had an LSD. The majority were white (80%), non-Hispanic/Latino (HL) (91%), aged ≥65 years (60%), married (75%), residents in metropolitan areas (88%), and had an annual house income of ≥$70,000 (70%). Multivariable logistic regression identified Black (OR: 1.24; 95%CI: 1.22-1.27), Asian or Pacific Islander (1.35; 1.30-1.40), and American Indian/Alaska Native (1.70; 1.53-1.89) to have higher odds of LSD compared to White patients (Table). In addition, HL ethnicity compared to non-HL (OR: 1.45; 95% CI: 1.42-1.49), age ≥65 compared to <65 (1.68; 1.65-1.71), unmarried status compared to married (1.88; 1.85-1.91), residency in non-metropolitan areas compared to metropolitan (1.10; 1.07-1.12), and household income <$70,000 compared to ≥$70,000 (1.03; 1.01-1.05) had a significant association with LSD. Conclusions: Older, non-White (Black, Asian/Pacific Islander, American Indian/Alaska Native), Hispanic/Latino, unmarried men, residents of non-metropolitan areas, or those with lower annual household incomes have higher odds of late-stage diagnosis. Interventions targeting early detection in these at-risk groups may improve prostate cancer outcomes in the US. Variable Odds Ratio (95% CI) p-value Race (Black vs White) 1.24 (1.22-1.27) <0.01 Race (Asian or Pacific Islander vs White) 1.35 (1.31-1.40) <0.01 Race (American Indian/Alaska Native vs White) 1.70 (1.53-1.89) <0.01 Ethnicity (Hispanic/Latino vs non-/Hispanic/Latino) 1.45 (1.42-1.49) <0.01 Age (≥65 vs <65) 1.68 (1.65-1.71) <0.01 Marital status (unmarried vs married) 1.88 (1.85-1.91) <0.01 Residence status (non-metropolitan vs metropolitan) 1.10 (1.07-1.12) <0.01 Household income (<$70,000 vs ≥$70,000) 1.03 (1.01-1.05) <0.01

Abstract Background Cholangitis is a well-described adverse event (AE) following endoscopic retrograde cholangiopancreatography (ERCP) that is associated with significant morbidity and mortality. Despite this, contemporary characterization of this AE using high-quality prospective data is incomplete. Aims In this study we describe post-ERCP cholangitis incidence, risk factors, and outcomes in a large, international multicenter population of patients undergoing ERCP. Methods We analyzed prospective data from nine centers in Canada, USA, and Europe between 2018-2024 with 30-day follow-up. The primary outcome was post-ERCP cholangitis, defined as (1) temperature &lt;36.0°C or &gt;38.0°C or white blood cells &lt;4 x109/L or &gt;10x109/L, (2) accompanying rise in bilirubin or transaminases to &gt;1.5 times the upper limit of normal or any increase compared to pre-procedure, and (3) emergency department visit or hospital admission and/or prolongation of existing admission. Multivariable logistic regression was performed to identify risk factors, with results presented as odds ratios (OR) with associated 95% confidence intervals. Outcomes following cholangitis were also described. Results Post-ERCP cholangitis occurred following 134 (1.7%) of 8,119 ERCPs (mean onset of symptoms 2.0 days). Repeat ERCP was required in 53.7% of these cases. Mortality attributed to cholangitis occurred in 8.2% of incident cases. Male sex (OR 1.48, 1.02-2.19), longer procedural time (OR 1.01, 1.00-1.02 per additional minute) and presence of a biliary stricture (OR 3.24, 1.98-5.30) were all independent risk factors for post-ERCP cholangitis, while placement of a biliary stent (OR 0.59, 0.36-0.95), and biliary sphincterotomy (OR 0.59 0.39-0.87) were both protective against post-ERCP cholangitis. Conclusions Post-ERCP cholangitis is common and associated with high mortality rates. Adequate pre-procedural counseling and early recognition is advised, especially in patients at increased risk. Funding Agencies None