Browse Articles

Individual patient data (IPD) analysis of early PSA nadir in ARASENS, LATITUDE, and TITAN: Training and validation of a novel model.

192 Background: Early PSA nadir after systemic therapy in mHSPC is a predictor of overall survival. There are no prediction models that have been validated in randomized clinical trials (RCTs) to help identify patients who experience early PSA response. Using IPD from three phase III randomized trials, ARASENS, LATITUDE, and TITAN, we trained and validated a model to predict early PSA nadir in mHSPC patients. Methods: Eligible trials that randomized mHSPC patients to receive an androgen receptor pathway inhibitor (ARPI) were identified through Medline and clinicaltrials.gov. Three trials were identified that had available IPD through online data-sharing portals, and a pre-specified analysis plan was approved. Early PSA nadir was defined as ≤0.2 ng/mL by 6 months of random allocation. Patients who received androgen deprivation (ADT) (+/- docetaxel [doce]) with ARPI, were split randomly 60:40 into a training and a testing cohort. Patients who received ADT monotherapy (+/- doce) as standard of care (SOC) were used as a validation cohort. A random forest classifier model was constructed in the training cohort with 10-fold cross-validation. Included variables were age, performance status, body mass index (BMI), Gleason score, metastatic stage at diagnosis, visceral metastasis, PSA and hemoglobin at baseline, use of docetaxel, and receipt of prior local therapy (RP and/or RT). After internal validation in the testing cohort, the locked model was applied to the validation cohort, and performance was assessed with area under curve (AUC) and Brier score. Results: Data was available for 3434 patients. Overall, 1718 patients received SOC plus ARPI and 1716 patients received SOC alone. The training cohort consisted of 1030 patients while the testing cohort and validation cohort consisted of 688 and 1716 patients, respectively. The top 5 variables in order of importance were baseline PSA, hemoglobin, BMI, age, and ECOG performance status. The AUC for the testing and validation cohort was 0.75 and 0.77, respectively. When stratified by tertile of predicted probability, the proportion of PSA nadir was 32%, 52%, and 83% in the testing cohort and 7%, 15%, and 41% in the validation cohort, respectively. The Brier scores for the testing and validation cohort were 0.20 and 0.26, respectively. The modest calibration (i.e., higher Brier score) in the validation (SOC alone) cohort could be attributed to slight overprediction of early PSA nadir probability by a model trained in SOC plus ARPI group. Conclusions: To our knowledge, this is the first trained and validated model to predict early PSA nadir by 6 months of treatment initiation in mHSPC using data from multiple phase III RCTs. This model could provide clinical utility to guide treatment and monitoring strategies, as well as conducting clinical trials to enrich patient accrual for those clinically impacted by early PSA nadir.

Identifying children who develop severe chronic kidney disease using primary care records

Background Understanding whether symptoms suggestive of chronic kidney disease (CKD) are reported to primary care before diagnosis may provide opportunities for earlier detection, thus supporting strategies to prevent progression and improve long-term outcomes. Our aim was to determine whether symptoms/signs or consultation frequency recorded in primary care could predict a subsequent diagnosis of chronic kidney disease in children. Methods We undertook a case-control study within Clinical Practice Research Datalink. Cases were children <21 years with an incident code for severe CKD during the study period (January 2000-September 2018). Controls were matched on age (+/-3 years), sex, and practice-level kidney function testing rate. Conditional logistic regression modelling was used to identify symptoms predictive of severe CKD and differences in consultation frequency in 24- and 6-month timeframes before the index date. Results Symptoms predictive of severe CKD in the 24 months before the index date included growth concerns (OR 7.4, 95% CI 3.5, 15.4), oedema (OR 5.7, 95% CI 2.9, 11.2) and urinary tract infection (OR 3.3, 95% CI 2.1, 5.4); within 6 months of the index date, effect estimates and specificity strengthened although sensitivity decreased. Overall, positive predictive value of symptoms was low. Cases consulted more frequently than controls in both timeframes. In combination, symptoms and consultation frequency demonstrated modest discrimination for CKD (c-statistic after bootstrapping 0.70, 95% CI 0.66, 0.73). Conclusion Despite increased consultation frequency and several symptoms being associated with severe chronic kidney disease, the positive predictive value of symptoms is low given disease rarity making earlier diagnosis challenging.

Psychometric validation of the 20-item K-DOCS in Chinese adolescents: a multi-method approach

Difference in renal cell carcinoma (RCC) prevalence between kidney transplant versus other solid organ transplant patients.

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.

Clinically advanced urothelial bladder cancer (CAUBC) in young onset bladder cancer (YOUC) patients: A genomic landscape study.

666 Background: CAUBC (any patients with node positive, metastasis positive or inoperable T4 disease) arising in YOUC is a challenging disease with significant need for improvements in systemic therapy especially for patients with surgically incurable disease. Methods: 9,411 cases of CAUBC underwent comprehensive genomic profiling (CGP) to examine all classes of genomic alterations (GA). MSI high status, tumor mutation burden (TMB) levels, genomic ancestry and trinucleotide mutational signatures were determined from the sequencing data. HRDsig status was calculated using a broad set of genome-wide copy number features (PMID 37769224). PD-L1 was determined by IHC using the Dako 22C3 tumor proportional score (TPS) system. Results were compared using the Fisher exact system with the Benjamini-Hochberg adjustment to correct for false discovery. Results: 291 (3.1%) CAUBC developed in YOUC patients under the age of 50 (CAUBC<50). The GA and biomarkers were compared with 9,120 CAUBC that developed in patients 50 years of age and older (CAUBC>50). The male gender preponderance in the CAUBC>50 was greater than in the CAUBC<50 cases (75.1% vs 69.4%; p=.069). The GA/tumor were higher in the CAUBC>50 (8.0 vs 7.0; p<.0001). Genomic ancestry distribution revealed significantly more Admixed American cases in the CAUBC<50 (8.9% vs 5.2%; P=.033) and more European cases in the CAUBC>50 (85.3% vs 74.9%; P<.0001). MSI high status was extremely uncommon (range 0.3% to 0.8%; NS). The frequency of TMB > 10 mutations/Mb was higher in the CAUBC>50 patients (35.1% vs 28.5%; P=.048). An APOBEC trinucleotide signature was more frequent in the CAUBC>50 patients (32.5% vs 25.8%; p=.041). PD-L1 low expression (1-49% TPS) was available in small subsets of cases and was similar in both groups (21.5% vs 28.5%; p=.84). GA in KMD6A (26.6% vs 14.8%; p=.0001), ERBB2 (18.4% vs 16.8%; p=.85.), ERBB3 (6.3% vs 6.5%; p=.91) MTAP (25.0% vs 20.3%; p=.27) and TERT (78.0% vs 68.4%; p=.005) were more frequent in CAUBC>50 cases and GA in HRAS (4.8% vs 2.1%; p=.11) and CCND1 (16.2% vs 13.1%; p=.35) were more frequent in the CAUBC<50 cases. GA in FGFR1 (4.1% vs 5.2%; p=.71), FGFR3 (14.1% vs 17.9%; p=.31), PIK3CA (20.3% vs 21.3%; p=.91) and PTEN (6.5% vs 4.5%; p=.31) were similar in both groups. Conclusions: In review of the CGP data, in contrast with CAUBC arising in older patients > 50 years of age, CAUBC arising in YOUC patients <50 years features a unique patten of biomarker and GA distribution that has potential to influence therapy selection and guide future clinical trials. CAUBC 0-49 years CAUBC >50 years P-value Sex (% male) 69.4% 75.1% .069 AMR ancestry 8.9% 5.2% .033 EUR ancestry 74.9% 85.3% <.0001 FGFR3 14.1% 17.9% NS KDM6A 14.8% 26.6% .0001 MTAP 20.3% 25.0% NS TERT 68.4% 78.0% .005 TMB>10 mut/Mb 28.5% 35.1% .048 APOBEC Signature 25.8% 32.5% .041

Differences in incidence and clinicopathologic features of secondary bladder cancer after long-term follow-up of brachytherapy and radical prostatectomy for localized prostate cancer.

381 Background: Although there studies have been reported that brachytherapy (BT) for prostate cancer is associated with an increased incidence of metachronous urinary bladder cancer (MBC), few studies have clarified differences in the clinicopathological features (CPF) of MBC between BT and prostatectomy (RP). We studied the risk and clinicopathological CPF of MBC between RP and BT groups in our hospital after long-term follow-up. Methods: Five hundred four patients treated with BT and 471 referred patients treated with RP between 2006 and 2017 in our hospital were reviewed. We compared the incidence of MBC and the CPF including the tumor number, location within the bladder, histology, and time from BT or RP to the MBC occurrence between BT and RP. The differences between the two groups were analyzed. Furthermore, in the BT group, the radiation dose distribution within bladder was estimated. Results: A total of 11 cases of MBC occurred in the BT group (2.2%) and 7 in the RP group (1.5%) after a median follow-up time of 107 months (13-209). The median time from initial treatments to the occurrences of MBC was 65 months (12-121) in BT and 100 months (4-126) in RP (p=0.469). Average tumor number was not significantly different between the groups (BT:1.4, RP:1.9, p=0.589). The tumor locations of MBC within the bladder for BT vs. RP were 9 vs. 1 in the lateral wall, 0 vs. 4 in the posterior wall, 0 vs. 3 in the dome, and 1 vs. 0 in the trigone. The incidence in the lateral wall was significantly higher in BT than in RP (p=0.001). Their median radiation dose of right wall (15.7±7.74Gy) and left wall (13.0±5.85Gy) showed no significant difference compared to the BT patients without MBC. There were 3 muscle-invasive cases in BT and 1 in RP (p=0.60). High-grade urothelial carcinoma occurred significantly more in BT (10 cases) than in RP (1 case) (p=0.001). According to the criteria, six MBC were judged as radiation-induced secondary bladder cancer. Conclusions: Long-term follow-up showed that the risk of MBC after BT was similar to that after RP. MBC after BT occurred significantly more frequently in the lateral wall and had a higher grade compared to those after RP.

Enhancing contact recommendation in social platforms through mental health awareness: Exploring Anorexia Nervosa as a case study

We analyze and propose a solution for the exposure of vulnerable users to harmful content during their interaction with contact recommender systems in social platforms. Our approach is dedicated to maximizing the number of harmless accounts suggested to users at risk. For these users, the over-personalization of recommender systems can result in an exposure to triggering content. We consider anorexia nervosa as a use case. People with anorexia tend to seek accounts of peers that support their unhealthy habits. Contact recommender systems can unintentionally reinforce such behaviors. Our approach modifies the objective function of a content and topology-based recommendation algorithm to maximize the suggestion of harmless accounts for users at risk. This is done with data from Twitter of Spanish speaking users with anorexia. The design and evaluation of the proposal has involved the participation of clinicians and volunteers at the last stages of treatment. Results show that users with anorexia are willing to follow harmless accounts suggested in online platforms. There is a tradeoff in precision (Pr) when comparing our proposal (Pr = 0.41) with a regular recommendation approach (Pr = 0.58). However, results are promising as there is a 55% increase in the percentage of harmless accounts suggested.

Study on bearing strength of fiber reinforced polymer anchoring cable in deep roadway

A comparative analysis of complication rates in urinary diversions: Exploring the impact of contemporary surgical trends.

751 Background: Historically, outcomes have been similar among patients undergoing continent (CD) and incontinent diversion (ID) at time of radical cystectomy (RC), with no difference in complication rates. Given the decreasing rates of CD, we sought to examine postoperative complication rates based on type of diversion in a contemporary cohort. Methods: Data was extracted from the NSQIP database from 2019-2021 who underwent RC. Patients were stratified based on diversion type. Statistical endpoints included thirty-day complications, length of stay (LOS), and readmissions. Optimal RC outcome was defined as absence of any postoperative complication, reoperation, prolonged LOS (75th percentile, 8 days) with no readmission. Multivariable analyses with Bonferroni correction were performed to assess the association between urinary diversion and postoperative outcomes. Results: A total of 4375 patients were identified, including 3780 (86.4%) who underwent ID and 595 (13.6%) who underwent CD. Compared to patients with CD, those with ID were more likely to be older, female, have higher ASA, worse renal function, robotic/lap approach, history of radiation or pelvic surgery, and higher stage (Table). On multivariable analysis, after Bonferroni adjustment, patients with CD had increased odds of high grade complications (OR 1.58; 99% CI [1.15-2.15]) and readmission (OR 1.7 [1.28-2.27]) as well as lower odds of an optimal outcome (OR 0.74 [0.58-0.95]) compared to incontinent diversion. Conclusions: In a contemporary cohort of patients undergoing RC, odds of adverse postoperative outcomes were increased among those undergoing CD compared to ID, despite more favorable baseline characteristics in this cohort. Preoperative and operative characteristics for patients undergoing radical cystectomy procedures stratified by diversion type. Incontinent Continent P-value Characteristic N=3780 N=595  Age 72.0 [65.0;77.0] 63.0 [57.0;69.0] <0.001  Sex: 0.001 Female 734 (19.4%) 80 (13.4%) Male 3046 (80.6%) 515 (86.6%) Year of Surgery: 0.33  2019 1450 (38.4%) 240 (40.3%)  2020 1601 (42.4%) 255 (42.9%)  2021 729 (19.3%) 100 (16.8%) ASA: <0.001  <3 752 (19.9%) 185 (31.1%)  ≥3 3028 (80.1%) 410 (68.9%) eGFR 68.3 [51.8;87.3] 77.3 [62.7;92.8] <0.001 BMI 27.8 [24.7;31.6] 27.5 [24.9;31.1] 0.704 Chemotherapy 1320 (34.9%) 276 (46.4%) <0.001 Radiation 346 (9.15%) 22 (3.70%) <0.001 Prior Pelvic Surgery 1863 (49.3%) 258 (43.4%) 0.008 Surgical Approach: <0.001  Open 2672 (70.7%) 467 (78.5%)  Hybrid 185 (4.89%) 20 (3.36%)  Lap/Robo 923 (24.4%) 108 (18.2%) OR Time 312 [240;393] 369 [280;465] <0.001 # Nodes 16.0 [10.0;25.0] 17.0 [11.0;26.5] 0.001 AJCC Stage: <0.001  0a-II 1833 (48.5%) 370 (62.2%)  III-IV 1947 (51.5%) 225 (37.8%) ASA: American Society of Anesthesiologist classification. BMI: body mass index. OR: operating room. AJCC: American Joint Committee on Cancer. # of nodes: median, [IQR].

Whole-slide multiplexed tissue imaging of prostate adenocarcinoma to investigate immune niches in high- versus low-grade tumors.

224 Background: The tumor-immune microenvironment (TME) is crucial in the progression of prostate cancer (PCa), yet little is known about its spatial organization and immune composition in treatment-naïve, localized PCa. While immunotherapy has had limited success in metastatic PCa, its efficacy in localized disease remains largely unknown. This study aims to dissect tumor-immune interactions in primary PCa and explore differences in immune landscape between low- and high-Gleason PCa, thus providing biologic insights for immunotherapy actionability. Methods: We performed spatial profiling of radical prostatectomy (RP) specimens from 28 treatment-naïve prostate cancer patients. These included 14 patients with low-grade disease (Gleason Grade Group 1–2) and 14 patients with high-grade disease (Gleason Grade Group 4–5). Using multiplex cyclic immunofluorescence (CyCIF) and a 27-marker panel, we obtained single-cell resolution across whole-slide images. Tumor and stromal compartments were manually annotated, and immune cell densities and neighborhood were analyzed and compared between low- and high-grade tumors. Spatial analysis focused on identifying immune clusters (IC -suggestive of tertiary lymphoid structures -TLS) and quantified the degree of immune infiltration along with characterization of T cell exhaustion markers such as CD8+PD1+TCF1+ cells. Results: High-grade tumors exhibited significantly higher infiltration of CD8+ T cells and CD20+ B cells compared to low-grade tumors. Spatial profiling revealed organized ICs, especially in high-grade tumors, which exhibited characteristics consistent with TLS. These ICs were enriched with precursor-exhausted CD8+PD1+TCF1+ T cells (TPEX), suggesting a state of immune exhaustion that may be therapeutically reactivatable. The presence of TLS and immune exhaustion markers in high-grade tumors highlights a more active immune microenvironment than previously appreciated in primary prostate cancer. Conclusions: Our findings reveal that a subset of high-grade prostate cancers harbor an organized, immune-infiltrated tumor microenvironment, including adaptive immune features such as TLS and CD8+ T cell exhaustion. These immune landscapes, marked by significant CD8+ and CD20+ cell infiltration and spatial clustering, suggest that high-grade prostate tumors may be amenable to immune-based therapies, despite the failure of immune checkpoint blockade in metastatic PCa. These results raise the hypothesis that immunotherapy might be effective in treatment-naïve high-grade prostate cancer. Future efforts should explore whether these immune profiles can be leveraged for risk stratification or as biomarkers for response to immunotherapy in advanced disease.

Impact of perioperative acute kidney injury on future renal outcomes in patients who undergo radical cystectomy: A multi-institutional retrospective cohort study.

879 Background: Acute kidney injury (AKI) is one of the frequent complications in patients who undergo radical cystectomy (RC). Although AKI has been reported to have a negative impact on renal outcomes in several diseases, the impact of perioperative AKI on major adverse kidney events (MAKE) in patients who undergo RC remains unclear. Methods: This multi-institutional retrospective cohort study included 702 patients with muscle invasive bladder cancer who underwent RC. AKI was defined according to the KDIGO criteria. Patients were divided into two groups: patients who developed AKI after RC (AKI group) and patients who did not (non-AKI group). MAKE was a composite of sustained ≥50% decline in eGFR, doubling of serum creatinine from the baseline, and sustained decrease in eGFR to <15 ml/min/1.73m 2 . The laterality and grade of hydronephrosis at the time of MAKE onset or last follow-up were evaluated. Multivariable Cox-proportional hazards regression analysis was performed to evaluate the impact of perioperative AKI on MAKE-free survival. Results: The median age and follow-up period were 70 years and 48 months, respectively. Of the 702 patients, 368 (52%) developed AKI after RC, with 26% having severe AKI (stage 2-3). Significant declines in eGFR at one-, three, and five-year after RC were observed in the AKI group compared with those in the non-AKI group ( P <0.001, P <0.001, and P <0.001, respectively). MAKE-free survival in the AKI group was significantly shorter than that in the non-AKI group ( P <0.001). After adjustment for confounding variables, including age, comorbidity, preoperative renal function, and hydronephrosis, AKI was independently and significantly associated with shorter MAKE-free survival (Table). Conclusions: Perioperative AKI had a negative impact on future renal outcomes in patients who underwent RC. Multivariable analysis for MAKE-free survival. Factor P value Hazard ratio 95% CI Age Continuous 0.730 1.005 0.978–1.033 Body mass index Continuous 0.051 1.068 1.000–1.142 Hypertension Presence 0.454 1.182 0.762–1.834 Dyslipidemia Presence 0.187 1.397 0.850–2.296 Diabetes mellitus Presence 0.370 1.257 0.762–2.072 Preoperative eGFR Continuous 0.146 0.990 0.977–1.003 Grade of hydronephrosis Continuous <0.001 1.509 1.206–1.888 Laterality of hydronephrosis Bilateral 0.301 0.734 0.409–1.318 AKI Positive 0.003 1.932 1.254–2.977

The role of peer support in coping and adjustment to dialysis and transplantation: Study protocol

Introduction People with kidney failure receiving dialysis or kidney transplantation find it difficult to adapt to treatment related routines and restrictions, and feel frustrated when their expectations aren’t matched by their lived experience. Health professionals provide information to help people prepare for kidney treatments, but it may be that ‘peer supporters’ - people who live with kidney disease - can provide more easily understood and relevant information. This study will explore how learning from peer supporters might improve the experience of treatment, after dialysis initiation and post-transplantation, by helping them to better understand what to expect from treatments. Methods Two mixed methods studies including in-depth interviews and questionnaires. In each study, participants will be recruited at two timepoints, before commencing dialysis or transplantation, and 6 months later. Questionnaires and interviews will explore expectations and the lived experience of treatment, and if peer support impacts on adjustment and coping with treatment. Participants will be recruited from two large teaching hospitals in the North and South of England, where one has access to a formal kidney peer support program. Discussion Delivering peer support in kidney units is increasingly popular, yet provision is inconsistent and generally low quality. Providing an evidence base for it’s use will help guide the optimal development of peer support programmes and efficient allocation of peer resources. A report will be produced to summarise the our findings, which will help kidney units better help people with kidney failure prepare for kidney treatments.

A novel method for detecting SARS-CoV-2 IgM and IgG based on the gold immune chromatography assay

Real-world (RW) treatment (tx) patterns and clinical outcomes in patients (pts) with metastatic renal cell carcinoma (mRCC) in the US community setting.

470 Background: Multiple approved immunotherapy (IO)-based combination regimens have demonstrated efficacy as first-line (1L) tx for mRCC, but have also shown notable toxicity. These factors may lead to variations in how tx regimens are used in RW community oncology care. No direct, prospective comparison exists for FDA-approved IO-IO or IO + tyrosine kinase inhibitor (IO-TKI) combination regimens in mRCC. This study assessed 1L TKI dosing patterns and RW outcomes of pts with mRCC in a large network of US community oncology practices. Methods: A retrospective, observational, matched cohort study was conducted among pts diagnosed with mRCC in The US Oncology Network IKnowMed electronic health record database. Eligible pts were ≥21 years old at initial diagnosis; initiated 1L tx in the metastatic setting with an IO-IO (ipilimumab [ipi] + nivolumab [nivo]) or IO-TKI (nivo + cabozantinib [cabo], pembrolizumab [pem] + axitinib [axi], or pem + lenvatinib [len]) combination regimen between Jan 1, 2021 and Apr 30, 2023; and had ≥1 post-treatment visit or a record of death during the study observation period (Jan 1, 2021 – Oct 31, 2023). Across cohorts, pts were exactly matched on IMDC risk score, sex, and age (<60y or ≥60y). Initial TKI dosing prescribed was summarized descriptively. Time to next treatment (TTNT) and overall survival (OS) were analyzed using the Kaplan-Meier method and univariable Cox regression. Results: A total of 308 pts, 77 in each cohort, were included with a median follow-up time of 11.0, 14.1, 8.8, and 9.2 months (mo) in the ipi + nivo, nivo + cabo, pem + axi, and pem + len cohorts, respectively. Across cohorts, 64% were male, 75% were ≥60 years of age (mean age, 65.1-66.9y), and IMDC risk score was as follows: 18% favorable, 51% intermediate, 21% poor, and 10% unknown. RW TKI dosing patterns and efficacy outcomes are described in the table.More pts initiated len (29.9%) below the recommended dose relative to cabo (15.6%) and axi (11.7%). The nivo + cabo cohort had a numerically longer median TTNT (14.3 mo) compared with the pem + axi (10 mo) and pem + len (9.4 mo) cohorts. Conclusions: TTNT analysis in a matched population suggests benefit of nivo + cabo in pts with mRCC in the RW 1L setting compared with other IO-TKI combinations. Dosing patterns suggest more pts may start len below the recommended dose relative to other TKIs. The highest 12-month OS was observed with nivo + cabo; however, additional follow-up is needed for more mature OS data. RW TKI dosing patterns and efficacy outcomes in 1L mRCC. IO-IO IO-TKI IO-TKI IO-TKI Variable Ipi + Nivo n=77 Nivo + Cabo n=77 Pem + Axi n=77 Pem + Len n=77 Initiated TKI below label recommended dose, n (%) NA 12 (15.6) 9 (11.7) 23 (29.9) Median TTNT, mo (95% CI) 8.4 (5.9-14.5) 14.3 (11.3-25.8) 10.0 (6.8-13.4) 9.4 (6.9-13.5) Hazard ratio (95% CI) 1.45 (0.96-2.18) ref 1.58 (1.04-2.38) 1.57 (1.04-2.37) 12-month OS estimate, mo 66.3 76.8 66.9 64.8

Patterns of split-dose gemcitabine and cisplatin (GC) use in patients with locally advanced or metastatic urothelial carcinoma (la/mUC): Results of a 10-country physician survey.

699 Background: Gemcitabine + cisplatin (GC) is a highly effective treatment for la/mUC. For patients who are ineligible for standard GC, split-dose GC is a promising alternative. This study aimed to provide insights into the use of split-dose GC and factors influencing treatment choice across 10 countries. Methods: Between January and March 2024, an international cross-sectional study was conducted via an online survey of physicians treating patients with la/mUC in Australia, Brazil, Canada, France, Germany, India, Italy, Spain, the UK, and the US. Demographics, practice patterns, and clinical parameters influencing treatment choice were collected. Multivariate logistic regression was used to determine factors influencing the use of split-dose GC. Results: The study included 791 physicians, mostly male (73%), who had a mean age of 43 years and an average of 13.2 years in practice, with 59% in academic practice. Most (85%) reported using split-dose GC across different treatment settings, including in 41% in neoadjuvant treatment, 40% in adjuvant treatment, and 43% in the metastatic setting. Physicians with the following characteristics were more likely to use split-dose GC: longer time in practice (per 10 years: odds ratio [95% CI], 1.58 [1.18-2.16]), higher patient volume (per 10 patients: 1.06 [1.01-1.14]), and public vs private practice (1.94 [1.27-2.97]). The preferred schedule in la/mUC was GC 35 mg/m 2 on days 1+8 of a 21-day cycle (57%). Most physicians (80%) used avelumab maintenance treatment after split-dose GC in patients without progression. The table shows acceptable lower thresholds for creatinine clearance (CrCl) reported by physicians for patients receiving split-dose GC. Conclusions: This large international survey underscores the extensive use of split-dose GC as an alternative regimen for patients with la/mUC who are ineligible for standard GC. Physicians who are more experienced and manage more patients are more likely to use split-dose GC. The results highlight the need for evaluating split-dose GC prospectively and establishing consensus guidelines for optimal use of split-dose GC in clinical practice and clinical trials. Physiciansn=635 CrCl in patients with ECOG performance status 0-1, n (%) 50 mL/min 573 (90.2) 40 mL/min 407 (64.1) 30 mL/min 195 (30.7) CrCl in patients with ECOG performance status 2, n (%) 50 mL/min 443 (69.8) 40 mL/min 290 (45.7) 30 mL/min 119 (18.7)

Comparing progression following systemic and tumor-directed therapy for <i>de novo</i> versus recurrent PSMA PET–defined oligo-M1 prostate cancer: A pooled analysis of SOLAR and SATURN clinical trials.

64 Background: Therapeutic strategies for oligometastatic castration sensitive prostate cancer (omCSPC) combining treatment of the primary and metastases with short-term intensified systemic therapy aim to improve survival and local control while minimizing toxicity from indefinite systemic therapy. This post-hoc analysis of the SOLAR (NCT03298087) and SATURN (NCT03902951) trials, which evaluated systemic and tumor-directed therapy in PSMA-PET defined oligo-M1 (≤5 metastases) de novo and recurrent omCSPC, respectively, aims to draw inferences on biology and oncologic outcome. Methods: All patients were treated with 6 months of systemic therapy: leuprolide, abiraterone acetate with prednisone, and apalutamide in conjunction with SBRT to oligometastatic sites. SOLAR patients were treatment naïve and underwent either radical prostatectomy (RP) with lymph node dissection followed by post-operative radiotherapy for high-risk features, or definitive radiotherapy (dRT). SATURN patients all had recurrent disease after RP with or without postoperative radiotherapy and may have also had prior hormone or metastasis-directed therapy. The primary endpoint (response rate) was the percentage of patients with an undetectable PSA (&lt;0.05 ng/mL) for post-RP patients, or a PSA &lt;2 ng/mL for post-dRT patients, six months after recovery of testosterone to &gt;150 ng/dl. Secondary endpoints included progression-free survival (PFS) and eugonadal PFS starting from time of testosterone recovery. Kaplan-Meier assessed differences in time-to-event endpoints from initiation of systemic therapy. Fischer’s Exact Test compared proportional outcomes. Results: Analysis included data from 24 SOLAR and 26 SATURN patients. Overall, median follow-up was 32 months (interquartile range 28.25-36.75 months). Response rates were higher for de novo versus oligorecurrent patients (20/24 [83%] versus 13/26 [50%], p=0.018). PFS and eugonadal PFS were also significantly longer (median not reached versus 17 months and median not reached versus 13 months, respectively, p&lt;0.05). PFS was shorter for oligorecurrent patients with prior exposure to hormone therapy (median 10 months versus not reached, p&lt;0.05). There was no PFS difference comparing patients treated in the de novo setting versus the recurrent setting who were naive to hormonal therapy (p=0.23). Conclusions: Patients with recurrent omCSPC PSMA-PET defined M1 disease had a worse response rate and shorter PFS following intensified systemic and metastasis-directed SBRT than those with de novo omCSPC. The difference was driven by recurrent patients with prior exposure to hormonal therapy, suggesting a continuum of treatment resistances over repeated courses of hormonal therapy. The majority of patients with de novo omCSPC remain in remission after gonadal recovery. Clinical trial information: NCT03298087 , NCT03902951 .

Hydrogeochemical and isotopic analysis for interpreting the formation of the complex geothermal system in the Guide Basin, Northeastern Tibetan Plateau

The Guide Basin, located in the northeastern Tibetan Plateau, is rich in geothermal resources. However, whether the genesis of all geothermal waters in the basin is consistent remains an unresolved question. To clarify the geothermal system in this area, this study investigated the hydrogeochemical and isotopic characteristics of geothermal waters, combined with an analysis of the distribution and properties of regional faults. The study analyzed the processes controlling the chemical composition of thermal waters and the reservoir temperatures, ultimately creating a conceptual model of geothermal fluids. The results indicate that the geothermal waters in the Luohantang and Zhacanggou areas are classified as Na-SO4·Cl type, while those in the Xinjie area are classified as Na-HCO3 and Na-HCO3·Cl type. The chemical composition of geothermal waters is primarily controlled by the weathering of silicates, with some influence from carbonate dissolution and cation exchange processes. Isotope data (δD, δ18O, and 87Sr/86Sr) indicate that all geothermal waters originate from atmospheric precipitation and undergo deep circulation. The heat source in Guide Basin comes from mantle heat flow and granite radioactive decay, but the thermal storage patterns in the three regions of the basin are different. The use of cation and silica geothermometers estimates the reservoir temperatures in the basin to range between 82.4 °C and 229 °C. This study enhances the understanding of the genesis of geothermal resources in the northeastern Tibetan Plateau and provides important information for guiding future geothermal exploration in the area.

Mechanisms of carbon and nitrogen distribution in soil aggregates in response to soil conditioners

Adjuvant nivolumab (NIVO) vs placebo (PBO) for high-risk muscle-invasive urothelial carcinoma (MIUC): Additional efficacy outcomes including overall survival (OS) in patients (pts) with muscle-invasive bladder cancer (MIBC) from CheckMate 274.

658 Background: In the phase 3, randomized, double-blind CheckMate 274 trial, adjuvant NIVO demonstrated statistically significant and clinically meaningful disease-free survival (DFS) benefit vs PBO in pts with high-risk MIUC after radical surgery (RS) ± prior neoadjuvant cisplatin-based chemotherapy (NAC). With extended 3-y median follow-up, continued improvements in DFS were seen with NIVO vs PBO in the primary efficacy populations (intent-to-treat [ITT], tumor programmed death ligand 1 [PD-L1] expression ≥ 1%) and in pts with MIBC. Early trends in interim OS favored NIVO vs PBO in ITT and tumor PD-L1 ≥ 1% pts. Here we report additional efficacy outcomes for pts with MIBC. Methods: Pts were randomized 1:1 to NIVO 240 mg every 2 wk or PBO for ≤ 1 y of adjuvant treatment, stratified by tumor PD-L1 expression, nodal status, and prior NAC. Primary endpoints were DFS in ITT and tumor PD-L1 expression ≥ 1% pts. OS in ITT and PD-L1 ≥ 1% pts was a secondary endpoint. Analysis of MIBC pts was exploratory. MIBC OS data are from preplanned interim analyses of ITT and PD-L1 ≥ 1% pts. OS follow-up is ongoing as the prespecified statistical boundaries for significance in ITT and PD-L1 ≥ 1% pts were not crossed at the time of these analyses. Results: Of 709 randomized pts (ITT), 560 (79%) had MIBC (NIVO, n = 279; PBO, n = 281); 284 (51%) of MIBC pts had prior NAC. With median follow-up of 36.1 mo (ITT), DFS improvement with NIVO vs PBO was consistent between all pts with MIBC (hazard ratio [HR] 0.63) and those with (HR 0.58) and without prior NAC (HR 0.69; Table). For OS, HRs favored NIVO vs PBO in all pts with MIBC (HR 0.70) and the tumor PD-L1 ≥ 1% subgroup (HR 0.48), as well as in pts with MIBC with (HR 0.74) and without prior NAC (HR 0.67). Safety was consistent with previous data in ITT pts; no new safety signals were identified. Conclusions: With 3-y median follow-up, consistent benefit in DFS was observed with NIVO vs PBO in all MIBC pts and across prior NAC subgroups. The HR for OS favored NIVO in all MIBC pts, in those with PD-L1 ≥ 1%, and regardless of prior NAC status. These results continue to support adjuvant NIVO as a standard of care for high-risk MIUC and MIBC, potentially providing an opportunity for a curative outcome. Clinical trial information: NCT02632409 . NIVOn NIVOMedian(95% CI), mo PBOn PBOMedian(95% CI), mo HR (95% CI) DFS All MIBC 279 25.6 (19.2–41.8) 281 8.5 (7.3–13.7) 0.63 (0.51–0.78) With prior NAC 142 19.6 (15.6–48.2) 142 8.3 (5.6–11.2) 0.58 (0.43–0.79) No prior NAC 137 25.9 (19.2–51.5) 139 13.7 (7.8–22.1) 0.69 (0.50–0.94) OS All MIBC 279 NR (45.0–NE) 281 39.9 (29.8–52.1) 0.70 (0.55–0.90) PD-L1 ≥ 1% 113 NR (NE–NE) 117 37.6 (26.9–NE) 0.48 (0.29–0.77) With prior NAC 142 55.2 (41.8–NE) 142 40.2 (28.8–53.7) 0.74 (0.53–1.03) No prior NAC 137 NR (40.7–NE) 139 37.7 (28.7–65.2) 0.67 (0.47–0.95) NE, not estimable; NR, not reached.

Updated results of the Tide-A study evaluating avelumab (Ave) plus intermittent axitinib (Axi) in previously untreated patients with metastatic renal cell carcinoma (mRCC).

551 Background: Combinations of therapies with VEGFR-TKI (TKI) and anti-PD1/PDL1 immunotherapy (IO) are considered the standard of care for first line treatment of patients (pts) with mRCC. The Tide-A trial previously reported the feasibility of TKI interruption and immunotherapy maintenance in pts achieving tumor response after TKI+IO combination, achieving its primary endpoint. Here we reported the updated results with a longer follow-up. Methods: Pts with surgery for primary tumor, without symptomatic/bulky disease or liver mets, were treated with Ave 800 mg flat dose IV Q2W + Axi 5 mg PO BID for 36 weeks (W). At W36, pts who achieved partial response (PR) interrupted Axi and continued Ave until progression of disease (PD) or unacceptable toxicity. In case of PD while on Ave, Axi was restarted and interrupted again in case of new PR. Pts without PR at W36 continue the combo until PD. Here we reported the updated results for mPFS and mOS in the overall population and in those pts who interrupted Axi. The outcome after Axi reintroduction was also described. Results: 75 pts were evaluated in the efficacy analysis (40% favorable risk, 60% intermediate/poor risk). At the cutoff data Apr 2024, after a median follow up of 31.7 mos, the mPFS was 27.9 mos (95%CI, 23.0 - 32.8) while the mOS was not reached and the 24-mos OS rate was 85%. The median duration of 1 st avelumab maintenance was 16 weeks. Among the 29 pts who interrupted Axi at W36, the mPFS and the mOS were not reached; while the 24-mos PFS and OS rates were 68% and 82%, respectively. After Axi interruption 5 pts were ongoing with avelumab without evidence of PD; 1 discontinued Ave for toxicity after 35.8 mos of maintenance; 2 patients continue Ave alone despite the evidence of PD;21 restarted Axi. Among these 21 pts, after the restart of axitinib, the ORR was 50% (10 pts PR; 8 pts SD; 2 pts PD; 1 pt NA), and the mPFS was 17.2 mos (95%CI, 11.9 – 22.5). Conclusions: Updated results of the TIDE-A study confirmed the feasibility of TKI interruption and IO maintenance in selected mRCC pts after initial response to first line combination of Ave plus Axi. The progression during maintenance with IO alone did not affect the response to the subsequent TKI reintroduction. This strategy warrants further investigation in a randomized trial. Clinical trial information: NCT04698213 .