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State of the genitourinary medical oncology workforce in the United States, 2024.

446 Background: There are approximately 13,400 oncologists engaged in patient care in the US as of 2022. As the field of medical oncology becomes subspecialized in not only academic but in community settings, it remains unclear unknown how many practicing oncologists identify as genitourinary medical oncologists. Methods: Using lists for the top fifty hospitals per state as ranked by US News & World Report, we identified practicing medical oncologists. We then identified those with a primary (100%) or predominant (50% or greater) areas of clinical focus in genitourinary oncology. We collected data on gender, race/ethnicity, and medical education. Results: We identified a total of total of 451 genitourinary medical oncologists in the United States. Of these, 399 (88.5%) practice in academic settings while 52 (11.5%) practice in community-based hospitals. 327 (72.5%) genitourinary medical oncologists are male, while 124 (27.5%) are female. 17 GU oncologists (3.8%) are from underrepresented minority groups in medicine. 321 oncologists (71.2%) were trained at US medical schools. 76 (16.9%) identified a particular organ (prostate, bladder, kidney, or testicle) as a clinical or research area of focus. The Northeast US had the most GU oncologists (n=150), followed by the South (n=129), West (n=97), and Midwest (n=75). Seven US states have no genitourinary medical oncologist. Conclusions: Medical oncologists with a primary or predominant focus in genitourinary cancers make up 3.4% of the medical oncology workforce in the US. Seven (14%) of US states do not have a self-identified genitourinary medical oncology expert. Gender and racial/ethnic disparities are present among the genitourinary medical oncology workforce. State of the workforce among genitourinary medical oncologists in the US. Number Male Female Underrepresented Minorities Focus Academic 399 285 114 15 Prostate (39), bladder (14), renal (18), testicular (2) Community 52 42 10 2 Renal (1), Prostate (2) Total 451 327 124 17

Carboplatin in patients with metastatic castration-resistant prostate cancer harboring somatic or germline homologous recombination repair gene mutations: Phase II single-arm trial (CiPHeR).

TPS291 Background: Approximately 20-25% of patients with metastatic castration resistant prostate cancer (mCRPC) harbour a germline or somatic mutation in the homologous recombination repair (HRR) pathway genes, which are involved in the repair of double stranded DNA damage. While polyadenosine 5’diphosphoribose [poly (ADP-ribose)] polymerase inhibitors, such as olaparib and rucaparib, are effective in this subgroup, their widespread use is limited due to the associated high cost, especially in resource-constrained settings. Platinum agents like carboplatin have exquisite sensitivity to cells with defective DNA repair machinery. Carboplatin, a conventional, inexpensive chemotherapeutic agent offers a potential alternative treatment in such patients. Several retrospective small case series support this hypothesis. However, there has been no prospective study evaluating the role of carboplatin in this subset of patients. Methods: This is an Investigator-initiated, prospective phase II, single-arm clinical trial in which patients diagnosed with mCRPC harbouring HRR pathway mutations previously treated with docetaxel or novel antiandrogen agents (abiraterone, enzalutamide, apalutamide, or darolutamide) or both will be eligible. Genes involved directly or indirectly in the HRR pathway will be tested by Next Generation Sequencing (NGS).We will screen approximately 200 patients to enroll 49 patients, and carboplatin (dosing at the area under curve=5) will be administered every 3 weeks until progression or intolerable side effects. The primary endpoint will be assessed as the proportion of patients with a reduction of serum prostate-specific antigen by more than 50% from enrolment. Using Simon’s two-stage design, 24 patients will be enrolled initially in the first stage. If at least 6 or more patients achieve a response, the trial will continue until enrolment of a total of 49 patients. Secondary outcomes include progression-free survival—soft-tissue disease progression (by response evaluation criteria in solid tumours, version 1.1, and bone lesion progression using Prostate Cancer Clinical Trials Working Group 3 criteria), health-related quality of life during carboplatin treatment using the Functional Assessment of Cancer Therapy—Prostate questionnaire and the European Organisation for Research and Treatment of Cancer questionnaire and safety profile of carboplatin (National Cancer Institute’s Common Terminology Criteria for Adverse Events version 5.0). The trial started enrolment in September 2023. The prespecified activity goal for the first stage of accrual was met; the second stage of accrual began in July 2024. This trial is ongoing and 30 patients have been recruited to date. All 49 participants will be enrolled according to plan. Clinical trial information: CTRI/2023/04/051507 .

LuCarbo: A phase 1a/1b trial of ¹⁷⁷ Lu-PSMA-617 (LuPSMA) with carboplatin in advanced prostate cancer.

TPS304 Background: LuPSMA is a proven life-prolonging therapy in men with metastatic castrate-resistant prostate cancer (mCRPC) who have previously received a taxane and an androgen receptor pathway inhibitor (ARPI). Despite patient selection by PSMA-PET/CT, responses are only seen in 50% of patients with PSMA-avid disease and are generally not durable. The mechanism of LuPSMA relies on delivery of beta emissions upon target engagement, thereby leading to DNA damage. Carboplatin is an inexpensive and widely available agent used as a radiosensitizer in other solid tumors and often combined with a taxane in CRPC. Given the need to improve outcomes with LuPSMA and the mechanisms of action of both agents, there is a rationale to evaluate the combination of LuPSMA with carboplatin in mCRPC. Methods: This is a single-center phase 1a/1b trial of LuPSMA and carboplatin. Patients with mCRPC who have previously received ≥1 taxane and ≥1 ARPI and have PSMA-avid disease on baseline PSMA-PET/CT are eligible. LuPSMA is given at the standard dose of 7.4GBq every 6 weeks, and carboplatin is dosed every 3 weeks, with 6 weeks constituting 1 cycle. In phase 1a, a 3+3 design is used with 3 planned dose levels of carboplatin (DL1 – AUC2; DL2 – AUC3: DL3 – AUC4); the dose-limiting toxicity (DLT) period is during cycle 1, and the recommended phase 2 dose (RP2D) will be the highest administered dose level with ≤1 DLTs out of 6 treated patients. In phase 1b, 19 patients will be enrolled at the RP2D (for a total of 25 patients treated at RP2D), and these patients will additionally undergo baseline and on-therapy research biopsies and an on-therapy PSMA-PET/CT after 2 cycles. The primary objective is to evaluate the safety of the combination and establish the RP2D; secondary objectives include overall response rate (PSA50 – reduction in PSA by ≥50% - and objective response rate, per RECIST 1.1), radiographic progression-free survival (per RECIST 1.1/PCWG3) and overall survival. Exploratory objectives include evaluation of genomic, transcriptomic, proteomic, and imaging biomarkers of response and resistance. With a sample size of 25 patients treated at RP2D, the combination will be deemed effective if 15 or more PSA50 responses are seen; the probability of concluding that the combination is effective is ≤0.1 if its true PSA50 rate is ≤45% and ≥0.9 if the true PSA50 rate is ≥70%. The study was activated in May 2024, and a total of 6 patients have been enrolled to date. Clinical trial information: NCT06303713 .

The recombinant spike S1 protein induces injury and inflammation in co-cultures of human alveolar epithelial cells and macrophages

The current lack of a straightforward and convenient modeling approach to simulate the onset of acute lung injury (ALI) has impeded fundamental research and hindered the screening of therapeutic drugs in coronavirus disease 2019 (COVID-19). The co-cultured human pulmonary alveolar epithelial cells (HPAEpics) and alveolar macrophages (AMs) were exposed to the complete medium, three concentrations of recombinant spike S1 protein (0.1, 1, and 10 μg/mL), or lipopolysaccharide (LPS) (10 μg/mL). The cells were harvested at 1, 2, and 3 days post-exposure. Lactate dehydrogenase (LDH) release, and IL-6, TNF-ɑ, and malondialdehyde (MDA) production were quantified and compared. Compared to those exposed to medium, co-cultures of HPAEpics and AMs exposed to a concentration of S1 protein at 10 μg/mL demonstrated significantly increased levels of LDH release (22.9% vs. 9.1%, and 25.7%), IL-6 (129 vs. 74, and 110 pg/mg of protein), and TNF-ɑ (75 vs. 51, and 86 pg/mg of protein) production, and similar to those exposed to LPS. However, no statistically significant differences were observed in MDA production. Compared to those harvested at 1 or 2 days post-exposure, co-cultured cells harvested at 3 days post-exposure exhibited increased levels of LDH release (23.4% vs. 14.9%, or 16.7%), IL-6 (127 vs. 81, or 97 pg/mg of protein) and MDA (5.6 vs. 3.2, or 3.8 nmol/mg of protein) production, but exhibited lower TNF-ɑ (58 vs. 79 pg/mg of protein) production than those harvested at 2 days post-exposure. After 3 days of exposure, co-cultures of HPAEpics and AMs showed significantly increased levels of LDH release (25.3% vs. 18.4%), and MDA production (5.5 vs. 4.3 nmol/mg of protein) compared to HPAEpics monocultures, and increased levels of LDH release (25.3% vs. 13.8%), IL-6 (139 vs. 98 pg/mg of protein) and MDA (5.5 vs. 4.7 nmol/mg of protein) production, and decreased TNF-ɑ (59 vs. 95 pg/mg of protein) production compared to AMs monocultures. Conclusions: The exposure to a concentration of S1 protein at 10 μg/mL in co-cultures of HPAEpics and AMs induced significant injury and inflammation three days post-exposure. This methodology for establishing a COVID-19-associated ALI model may have promising potential applications and value.

Variations of autonomic arousal mediate the reportability of mind blanking occurrences

Missed opportunity: PROMs as primary endpoints in bladder cancer trials.

682 Background: Bladder cancer is the sixth most common malignancy in the United States. Recent advances in treatment paradigm have changed the landscape of bladder cancer. Patient-reported outcome measures (PROMs) are measures of symptom burden and health related quality of life (HRQoL) that come directly from the patient, without clinician interpretation. PROMs can be the intervention and/or the outcome in a trial. We aimed to evaluate the trends in the usage of PROs for patients with muscle invasive bladder cancer (MIBC) and locally advanced or metastatic bladder (mBC) cancer as a measure of endpoints across global clinical trial databases. Methods: We searched the clinicaltrials.gov database for phase III trials involving muscle invasive, locally advanced and metastatic bladder cancer patients from 1990 to 2024. The data extraction included primary and secondary endpoints, PROMs, PRO parameters, and clinical trial duration. Descriptive statistics derived were used to summarize the data. Results: Fifty-four trials were included in the analysis, out of which 64.8% (n=35) were for mBC and 35.1% (n=19) for MIBC. Twenty-nine trials (53.7%) included PROMs as endpoint measures, more than half in MIBC (n=16, 55%). Approximately one third (n=13/35) of mBC included PROMs in their trials (37.1%) whereas (84.2%) included PROMs in MIBC trials (n= 16/19). None of the studies reported PROs as a primary outcome measure, twenty-three studies (79%) reported PROs as a secondary outcome, and only one (3.4%) reporting it as both primary and secondary outcome measure. In mBC nine trials (56.25%) in the 1 st line setting, six studies (37.5%) in the 2 nd line setting and one trial (6.25%) labelled as adjuvant after radiation. In MIBC trials, three studies (23%) were in the adjuvant setting, five studies (38%) in the neoadjuvant setting and one trial (8%) involving both adjuvant & neoadjuvant, and four studies (31%) in the chemoradiotherapy setting. Eleven different symptom domains were utilized to measure PROs across both the groups. The European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ C30) and the EuroQOL 5-dimension 5-level Questionnaire (EQ-5D-5L) were the most frequently utilized PRO scales, being used in 62.5% and 37.5% of PRO reporting studies respectively. Conclusions: PROMs are increasingly used in bladder cancer trials, especially for MIBC. Approximately one-third of the trials included PROMs, yet none utilized them as primary endpoints, indicating a missed opportunity to truly understand treatment impact from the patient's perspective. Future research should prioritize PROMs as primary outcome measures to ensure patient-centered care and improve quality of life for bladder cancer patients. Further efforts are needed to standardize the current available scales to measure PROs.

Clinical protocols to monitor efficacy of [ ¹⁷⁷ Lu]Lu-PSMA radiopharmaceutical therapy in metastatic castration-resistant prostate cancer.

39 Background: To assess the prognostic value of post-therapy [ 177 Lu]Lu-PSMA (LuPSMA)-SPECT/CT by visual RECIP 1.0 during LuPSMA radioligand therapy and to develop an evidence-based clinical protocol to monitor efficacy to LuPSMA. Methods: Patients who received LuPSMA between April 2019 and November 2023 and who underwent at least two LuPSMA-SPECT/CT (SPECT) were included. Three independent readers interpreted pairs of baseline and interim LuPSMA-SPECT/CT after 2 cycles of therapy for visual Response Evaluation Criteria In PSMA-imaging (RECIP) 1.0. The primary outcome was the prognostic value of post-therapeutic SPECT by RECIP 1.0 for overall survival after LuPSMA. The secondary outcome was the agreement between SPECT and PSMA-PET/CT (PET) performed after 2 cycles of LuPSMA. Results: 105 patients were included. In SPECT PD was associated with shorter OS compared to SD (HR=2.51;95%;CI:1.19-5.28;p=0.015) and to PR (HR=6.48;95%;CI:2.67-15.70;p<0.001). 73/105 (69.5%) had a PET after 2 cycles. 7/73 (10%), 30/73 41%), 22/73 (30%), and 30/73 (41%) patients had a tumor progression by SPECT, PET, SPECT+PSA, and PET+PSA, respectively. All 7/73 (10%) patients with PD by SPECT had PD by PET. The C-index for SPECT was inferior to the one of SPECT+PSA (0.54 vs 0.62; p=0.03) and PET (0.54 vs 0.66; p<0.001) while SPECT+PSA did not differ significantly from PET (0.62 vs 0.66; p=0.07). Conclusions: Post-therapeutic SPECT/CT by RECIP 1.0 after 2 cycles of LuPSMA therapy is prognostic for overall survival and can be used for treatment response evaluation purposes. PSMA-PET/CT identified significantly higher number of patients with progressive disease compared to LuPSMA-SPECT/CT. A composite classification system of LuPSMA-SPECT/CT+PSA was not significantly different from interim PSMA-PET/CT for response evaluation to LuPSMA.

ABCA1 and ABCG1 cholesterol transporters expression on metastatic renal cell carcinoma: Impact on immunotherapy outcomes (CHOMET study).

568 Background: Although immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, most patients do not achieve benefits, emphasizing the need to understand the mechanisms of resistance. Previous analysis highlighted the association between blood cholesterol levels, passive cholesterol diffusion efflux and oncological outcomes. Here we reported the preliminary data of the CHOMET study, aimed at assessing the cholesterol transporters ABCA1 and ABCG1 expression in ICIs-treated patients with metastatic renal cell carcinoma (mRCC). Methods: The present is a monocentric retrospective study on patients with mRCC receiving first-line ICI-based combination. The primary objective was to assess the ABCA1/G1 expression by immunohistochemistry and its impact on overall survival (OS). The secondary objectives included the impact on progression-free survival (PFS) and disease control rate (DCR: complete and partial responses plus stable disease). Survival times were calculated by Kaplan-Meier method and comparisons between groups were performed by log-rank test. Results: 61 patients were enrolled, clear cell RCC was the most frequent histotype (78.8%). With a median follow-up of 30.4 months (22.1-37.0), median OS was 38.9 months (CI 33.9-NR) and median PFS was 24.4 months (CI 10.1-34.2). For the present analysis, the ABCA1/G1 histological evaluation of tumour samples was available for 43 and 41 patients, respectively. The median expression level was 50% for ABCA1 and 45% for ABCG1. We found a significant correlation between higher ABCA1/G1 staining intensity expression and both shorter median OS and PFS (Table). Similarly they were inversely related to DCR (Table). Conclusions: For the first time, we reported a high expression of ABCA1/G1 cholesterol transporter on kidney cancer. An inverse association between staining intensity expression and oncological outcomes in patients receiving ICIs combinations was found. Oncological outcomes according to ABCA1/G1 staining intensity expression. IHC mPFS months (95%CI) mOSmonths (95%CI) DCR% ABCA1 intensity expression 1+ 30.1 (25.8-NR) NR (NR-NR) 88.9 2+ 24.4 (9.9-NR) NR (33.9-NR) 72.7 3+ 4.5 (3.20-NR) 12.2 (8.2-NR) 25.0 p value 0.016 < 0.001 0.013 ABCG1 intensity expression 1+ 62.7 (25.6-NR) NR (NR-NR) 87.5 2+ 17.4 (9.9-NR) NR (NR-NR) 68.2 3+ 6.65 (2.9-NR) 12.2 (3.8-NR) 37.5 p value 0.006 0.013 0.101 DCR: disease control rate, IHC: immunohistochemistry, mOS: median overall survival, mPFS: median progression-free survival, NR: not reached.

Impact of initial local therapy (LT) in the combination treatment era for metastatic renal cell carcinoma (mRCC): Subgroup analysis from ProPaxi study.

511 Background: Local therapy for managing metastatic sites may be a beneficial frontline approach for patients with mRCC. However, existing data are limited to retrospective studies involving patients treated mainly with tyrosine kinase inhibitors (TKIs). This study aims to characterize the initial LT approach prior to the initiation of immuno-TKI combinations. Methods: ProPaxi is a prospective observational study that enrolled pts treated with the Pembrolizumab/Axitinib (Paxi) combination as first-line therapy. We conducted a retrospective analysis of pts characteristics and outcomes when LT was used as a frontline approach. Results: From December 2020 to September 2023 ProPaxi study enrolled 170 pts, of whome 56 (33%) received LT as frontline therapeutic approach. The majority had clear-cell histology (86%). Approximately half of pts (46%) had synchronous metastasis and nephrectomy was performed in 60% of cases. Stratifying by IMDC criteria at the time of the start of systemic treatment, 11 pts (20%) were classified as favorable-risk, 32(59%) as intermediate-risk, and 12 (21%) as poor-risk. Additionally, around half of pts (52%) had time-to-treatment start longer than 1 year as prognostic factors; this was the only prognostic factor in 18% of cases. Bone was the most commonly treated metastatic site, accounting for 50% of cases, followed by the lung (14%) and brain (13%). The types of LT administered were as follows: radiotherapy (46%), surgery (43%), and other (11%). The objectives of treatment included: pain control (30%), curative treatment for local complications (29%), prevention of local complications (29%), and achieving complete response or delaying systemic treatment (30%). In one-fifth of patients (21%), there were multiple objectives for the local therapy. Radiotherapy was the most frequently used treatment for pain control, applied in 94% of cases. For managing local complications, surgery and radiotherapy were also common, accounting for 31% and 38%, respectively. Both treatments were equally utilized (38%) for the prevention of local complications. Surgery was the predominant approach for achieving complete response or delaying systemic treatment, used in 88% of cases. The mean time from metastasis diagnosis to treatment start was 7.9 months (95% CI: 4.1–11.2) for patients who received LT versus 2.5 months (95% CI: 1.9–3.1) for those who did not (p < 0.001). No significant differences were observed in progression-free survival (PFS) or overall survival (OS). Conclusions: This analysis describes for the first time the current approach to implementing LT for the management of mRCC. Thus, LT emerges as a valid and established option even in the era of immuno-TKI combinations. The objective of therapy appears to be the key factor in determining the choice of treatment in clinical practice.

Where is communication breaking down? Narrative tensions in obesity-in-pregnancy clinical encounters

There are numerous biomedical and psychosocial challenges associated with obesity in pregnancy that impede communication between healthcare providers (HCPs) and patients. We conducted a narrative study informed by stigma theory to understand specific areas of communication breakdown in obesity-in-pregnancy clinical encounters. Sixteen patients and 19 HCPs participated in in-depth, semi-structured interviews. We explored how participants positioned obesity-in-pregnancy clinical encounters within their broader narratives. Employing narrative analysis, we identified five narrative tensions contributing to communication challenges: 1) obesity as a detriment to health versus an acceptable biologic variation ; 2) obesity as the result of personal choice versus the result of uncontrollable circumstances ; 3) a regular pregnancy versus a high-risk diagnosis; 4) a typical and problem-free clinical encounter v ersus a tremendously difficult clinical encounter ; and 5) talking openly about Body Mass Index (BMI) and related co-morbidities versus sidestepping the topic . How participants positioned themselves relative to prevailing societal discourses regarding obesity in general influenced these tensions. These narrative tensions revealed specific areas where communication is vulnerable to breaking down during the obesity-in-pregnancy clinical encounter. Participants’ (both HCPs and patients) past experiences of clinical encounters–and the meanings they ascribe to them–shape subsequent encounters, and our analysis illuminates the complexities of this interactive space. This research has implications for improving clinical practice and education.

Mangroves, fauna compositions and carbon sequestration after ten years restoration on Flores Island, Indonesia

Somatic genomic landscape of prostate adenocarcinoma at a comprehensive cancer center in New Mexico: A retrospective study (2015-2022).

200 Background: Prostate cancer is the second leading cause of cancer-related deaths in men. In New Mexico, it is the leading cause of cancer death among specific populations, particularly American Indians and African Americans. This study investigates the frequency and diversity of somatic mutations in patients with prostate adenocarcinoma treated at the University of New Mexico Comprehensive Cancer Center (UNMCCC). Methods: We conducted a retrospective analysis of patients with prostate adenocarcinoma treated at UNMCCC from 2015 to 2022 who underwent screening for somatic mutations via next-generation sequencing (NGS). We evaluated these mutations and collected data on tissue type tested, race, ethnicity, and age. Descriptive analysis summarized frequencies of somatic mutations overall and across ethnic groups. Due to small sample sizes, randomization tests were performed to evaluate whether mutation rates within ethnic groups differed significantly from those expected based on the ethnic composition of the entire sample. Results: The study examined 61 patients (median age 63 years) including: 31 White (51%), 16 Hispanic (26%), 9 American Indian (15%), 4 African American (7%), and 1 Asian (2%). Of the patients tested, 52 underwent tissue-based NGS, 7 had liquid-based NGS, and 2 had both tests performed. The most prevalent genetic alterations were TMPRSS2-ERG fusion (48%), TP53 mutations (41%), PTEN loss/rearrangement (36%), and AR mutations (30%). Comparisons of mutation frequencies across ethnic groups revealed variations in mutation prevalence (Table 1) For most mutations, observed ethnic group frequencies did not differ significantly from expected frequencies based on the total sample (p>0.05), although statistical power was low to detect all but large differences. The exception was BRCA2, where ethnic group frequencies differed significantly from those in the total sample (p=0.025), with no Hispanic patients and equal numbers of White and Native American patients having the mutation. Conclusions: This study reveals complex prostate cancer genetic patterns across diverse New Mexican ethnicities. These findings have potential implications for targeted therapies and emphasize the need for larger, more diverse cohorts in research. Proportion of race and ethnic groups with each mutation. Mutation Number Positive Proportions Within Racial/Ethnic Groups Hispanic Native American Black White Asian TMPRSS2:ERG fusion 29 24.1% 17.2% 0.0% 55.2% 3.4% TP53 25 24.0% 8.0% 8.0% 60.0% 0.0% PTEN loss/frameshift 22 27.3% 13.6% 4.5% 54.5% 0.0% AR Mutations 18 27.8% 5.6% 5.6% 61.1% 0.0% MYC amplification 11 45.5% 9.1% 0.0% 45.5% 0.0% PIK3CA 7 28.6% 28.6% 0.0% 42.9% 0.0% RAD51 R/RAD21 AMP 7 57.1% 14.3% 0.0% 28.6% 0.0% BRCA2 6 0.0% 33.3% 16.7% 33.3% 16.7% BRCA1 3 66.7% 0.0% 0.0% 33.3% 0.0% ATM 3 0.0% 33.3% 0.0% 66.7% 0.0% All Screened 61 26.2% 14.8% 6.6% 50.8% 1.6%

Artificial intelligence–derived tumor volume from baseline MRI and postprostatectomy outcomes following neoadjuvant hormonal therapy for patients with high-risk prostate cancer.

330 Background: Neoadjuvant hormonal therapy (NHT) with androgen deprivation therapy and androgen receptor pathway inhibitor (ARPI) before radical prostatectomy (RP) has emerged as a potentially promising strategy for patients with high-risk prostate cancer (PCa), with several trials, including PROTEUS, which are investigating this approach. Early studies demonstrated that 20-25% of patients have a pathologic complete response (pCR) or minimal residual disease (MRD) after NHT with ARPI, which is highly prognostic for long-term outcomes. However, predictors of pCR/MRD remain poorly understood. We previously demonstrated that the total volume of intraprostatic tumor (V AI ) on prostate multiparametric MRI, determined using an artificial intelligence (AI) model, is independently prognostic in localized PCa treated with upfront RP or radiotherapy. Our objective was to examine the association between pre-NHT V AI and outcomes after RP. Methods: We identified 105 patients with high-risk PCa from 4 prospective trials of NHT with ARPI who had pre-NHT MRIs between 2009-2018. A deep learning model for segmenting the intraprostatic tumor was trained using nnU-Net v2 with a ResNet encoder with an independent cohort of 1776 patients with localized PCa and MRIs utilizing 5-fold cross-validation. An ensemble model was used to provide segmentations for held-out pre-NHT MRIs. We examined the association between V AI and likelihood of pCR/MRD (≤5mm residual tumor) using logistic regression, as well as associations between V AI and time to next therapy (TT) and metastasis-free survival (MFS) using univariable Cox regression. Results: 26 patients (24.7%) had pCR/MRD. Median pre-NHT V AI for patients with and without pCR/MRD were 0.87mL (interquartile range [IQR] 0.25-1.53) and 2.50mL (IQR 1.16-4.30), respectively. Increasing V AI was associated with decreased likelihood of pCR/MRD on multivariable analysis (adjusted odds ratio 0.97 per mL increase, 95% confidence interval [CI] 0.95-1.00, p=0.027). V AI had a greater area under the receiver operating characteristics curve than NCCN clinical risk groups (0.778 vs 0.511, p<0.001) for predicting pCR/MRD. After median follow-up of 6.3 years, the hazard ratios for associations between V AI and TT and MFS were 1.14 (95% CI 1.08-1.21, p<0.001) and 1.07 (95% CI 0.99-1.16, p=0.091), respectively. 6-year MFS rates were 94.4%, 87.0%, and 75.4% for V AI of 0-0.4, 0.5-1.9, and ≥2.0mL, respectively. Conclusions: A higher V AI on baseline MRI was associated with decreased likelihood of pCR/MRD and shorter time to next therapy after NHT and RP. If validated, AI-determined tumor volume has potential for becoming a clinically useful tool for the upfront identification of both patients most likely to benefit from NHT and RP, as well as those who should be considered for alternative treatment strategies.

Burden of cancer in metastatic renal cell carcinoma (mRCC).

467 Background: Combination regimens and sequencing of multiple agents have significantly improved clinical outcomes for patients (pts.) with mRCC. We sought to assess the burden of mRCC on patients and interference with daily life. Methods: The survey was developed by the Kidney Cancer Research Alliance (KCCure), and broadcast between 09/24 and 10/24 to pts. via website, mailing lists and social media platforms. Results: Of 1167 respondents, 492 pts. had received systemic therapy for mRCC. Median age was 58.7 years (range 17.2 - 87.0), 83% were from the United States. 42% were on first line treatment, 30% second line, 13% third line, and 15% in fourth or later line. 69% were on systemic on therapy with evidence of disease, 10% were receiving treatment with no evidence of disease, 13% had discontinued treatment with no evidence of disease; 8% had discontinued treatment with evidence of metastatic disease. 45% of pts. take ≥7 prescriptions per day, 11% take ≥10 prescription medications per day. One-third (33%) of pts. are concerned they are taking too many medications. In the last year, pts reported seeing 4.24 (range 1-17) different types of doctors for cancer related care. In the last 90 days: 36% have gone to the emergency room, 20% more than once. 96% had blood drawn at least once, 35% had ≥5 blood draws. 95% had at least one clinic visit, 22% ≥5 clinic visits. 30% had ≥5 pharmacy visits. 23% have been hospitalized, 12% for ≥5 days. In the last year, 45% were hospitalized at least once, 52% more than once, 11% ≥5 times. Hospitalizations and visits to the emergency room were significantly correlated with a lower quality of life and higher NCCN distress score (p<.001). 89% of pts think about cancer every day; 44% spend a few to several hours per day thinking about cancer. When asked how confident they feel about making plans, 33% feel completely confident making plans 6 months from now, 21% one year and 10% two years from now. Pts. with no evidence of disease are significantly more likely to rank their QOL as excellent (19%) compared to pts. with evidence of disease (4%), independent of treatment. Pts. who have discontinued treatment and still have evidence of disease rank their QOL as poor (17%). Conclusions: Pts. living with mRCC are physically and mentally consumed with cancer and disease management. mRCC disrupts fundamental daily activities, including eating, sleeping, and socializing. Pts. must routinely engage with the healthcare system, extensively managing scheduled and unscheduled appointments with multiple providers. Nearly all contemplate their cancer daily. More research is needed to improve care and alleviate disease burden in mRCC. Disruption of daily and routine activities. Activities Impacted by Cancer Frequency - Always or Often Eating a meal 37% Sleeping 38% Engaging with Friends 31% Grocery Shopping 25% Attending an Event 31% Buying Clothes 18% Traveling 43%

Association between baseline and changes in hemoglobin levels and treatment response and prognosis in metastatic renal cell carcinoma: A Mexican retrospective study.

518 Background: Clinical markers of response and outcome in metastatic renal cell carcinoma (mRCC) are lacking. Low hemoglobin (Hb) is associated with poor outcomes in the IMDC risk score. Hb levels also appear to be associated with mRCC response to VEGFI monotherapy, although this relationship is nuclear. This study evaluates the role of Hb increases as a predictive biomarker of clinical response and outcomes. Methods: Patients with advanced RCC treated with VEGF receptor tyrosine kinase inhibitors (TKIs) as a first-line therapy were identified. Hemoglobin levels were retrieved at baseline and then at monthly intervals for 6 months. Absolute and percentage increases over baseline were evaluated as predictors of objective response rate, progression free survival. Patients were categorized as responders (CR+PR) or nonresponders (SD+PD) using cross-sectional imaging at week 12. The Kaplan-Meier method was used to estimate PFS for patients who had an increase vs. decrease from baseline Hb, and the log-rank test used to assess survival differences between the groups. The Cox proportional hazards model was used for univariate and multivariate regression analysis to determine the significance of individual variables on PFS. Results: Among the 47 eligible patients, elevations in hemoglobin were observed in 64%. The median age at start of treatment was 59 years. Changes in hemoglobin at time of response were associated with objective response rate. Landmark analysis at 1 month showed that increases in hemoglobin were associated with longer PFS (mPFS 15 vs. 50 months; P = .004) Responders had a significantly higher Hb level than nonresponders at 1rs month P= 0.004. An increase in Hb was a significant independent predictor of progression-free survival (HR 0.47, P= .039). Conclusions: In this retrospective clinical study, we demonstrate that Hb levels are a valuable clinical marker of outcomes in patients receiving first-line therapy for mRCC in our population. These findings are readily applicable to routine clinical practice and may help clinicians deliver more personalized care.

Does patients’ age predict their clinical outcomes following non-infectious epiglottitis? A systematic review

Background Non-infectious epiglottitis, an infrequent but significant condition, presents challenges in airway management and treatment due to its potential for rapid progression. Objective To analyze differences in clinicodemographic characteristics, management strategies, and clinical outcomes between pediatric and adult cases of non-infectious epiglottitis. Methods A systematic search of four databases identified 57 patient records, all diagnosed with non-infectious epiglottitis. Children (<18 years) were compared to adults (≥18 years). Differences in clinicodemographic characteristics, management strategies, and clinical outcomes were analyzed. Outcomes included intubation, complications, and intensive care unit (ICU) admission. Risk factors of these outcomes were identified through uni- and multi-variable logistic regression analyses. Results Twenty-three children and 34 adults were analyzed. The presentation with stridor (56.52% vs. 14.7%), drooling (56.52% vs. 26.47%), cyanosis (17.39% vs. 0%), and sternal retraction (13.04% vs. 0%) was more common among children. Prior vaccination was evident in only 5 pediatric cases. The etiology of epiglottitis was similar across groups. Children had significantly higher chances of receiving epinephrine (34.78% vs. 8.82%), undergoing intubation (82.60% vs. 20.58%), being admitted to the ICU (56.52% vs. 17.64%), and having complications (47.82% vs. 14.70%), compared to adults. In the multivariate regression model, pediatric age was a risk factor for intubation (p = 0.015) and ICU admission (p = 0.040), while foreign body ingestion (p = 0.039) and dyspnea (p = 0.014) were predictors of intubation and complications, respectively. Conclusions The study highlights the necessity for age-specific management strategies in non-infectious epiglottitis. Understanding the distinct clinical presentations and responses in different age groups can lead to improved patient care.

Influence of biochar on the partitioning of iron and arsenic from paddy soil contaminated by acid mine drainage

Daily briefing: How did childhood evolve?

Cabozantinib real-world effectiveness in the second-line setting of metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).

479 Background: Cabozantinib is approved as a subsequent therapy for patients with metastatic renal cell carcinoma (mRCC) based on the METEOR trial. However, only 5% of patients in this trial received prior immunotherapy. Methods: We identified patients with mRCC from the IMDC who were treated with cabozantinib in the second-line (2L) setting from 2010 to 2023. These patients were stratified by IMDC risk groups and first-line (1L) treatment. We analyzed overall response rate (ORR), time to next treatment (TTNT), treatment duration (TD), overall survival (OS) and performed a multivariable analysis adjusted by IMDC criteria at 2L. Results: A total of 603 patients were identified. Baseline characteristics are summarized in the table. For the entire cohort, the ORR was 25.7%, TTNT was 10.1 months (mo), TD was 8.9 mo and mOS was 19 mo. Among patients treated with 1L ipilimumab/nivolumab (n=190), anti-PD1 + TKI (n=148), and TKI alone (n=207), cabozantinib showed an ORR of 27.2%, 26.4%, and 25%, respectively; a median TTNT of 9.9, 10.3, and 9.7 mo; a median TD of 9.4, 8.2, and 8.3 mo. Median OS was 18.6, 17.6, and 21.3 mo, respectively. A multivariable analysis was unable to demonstrate that first-line ORR (CR/PR vs SD vs PD) or TTNT (< 12 vs ≥ 12 mo) predicts for second-line cabozantinib ORR in the overall cohort and by first-line therapy type. Specifically, patients with stable disease or with partial and complete response in 1L were associated with an OR for a response of 0.99 (95% CI 0.52-1.92) or 1.23 (95% CI 0.61-2.49), respectively. Similarly, a first-line TTNT of ≥12 months had an OR for response of 1.04 (95% CI 0.59-1.82). Conclusions: This study demonstrates that cabozantinib maintains efficacy comparable to that observed in the METEOR trial in a real-world setting, including in patients with prior immunotherapy combination therapies. Efficacy of 1L treatment does not predict efficacy of 2L cabozantinib. Baseline characteristics. Variable Overall (N = 603) IO-IO (N = 190) IO-TKI (N = 148) TKI Alone (N = 207) Other (N = 58) p-value Non clear cell histology 107 (17.7) 33 (17.4) 26 (17.6) 28 (13.5) 20 (34.5) 0.003 Nephrectomy 416 (69.0) 97 (51.1) 110 (74.3) 166 (80.2) 43 (74.1) <0.001 1st line IMDC Risk Fav/Int/Poor 83 (13.8)/296 (49.1)/101 (16.7) 10 (5.3)/100 (52.6) /46 (24.2) 37 (25)/62 (41.9) /20 (13.5) 29 (14)/99 (47.8)/27 (13) 7 (12.1)/35 (60.3)/8 (13.8) <0.001 2nd line IMDC risk Fav/Int/Poor 56 (9.3)/269 (44.6)/108 (17.9) 7 (3.7)/90 (47.4)/45 (23.7) 25 (16.9)/63 (42.6)/24 (16.2) 19 (9.2)/87 (42.0)/32 (15.5) 5 (8.6)/29 (50.0)/7 (12.1) 0.002 Greater than 1 site of Metastasis 473 (78.4) 146 (76.8) 114 (77.0) 161 (77.8) 45 (77.6) 0.722 Brain Metastasis 36 (6.0) 18 (9.5) 5 (3.4) 13 (6.3) 0 (0.0) 0.022 Bone Metastasis 221 (36.7) 74 (38.9) 60 (40.5) 70 (33.8) 17 (29.3) 0.326 Liver Metastasis 106 (17.6) 32 (16.8) 26 (17.6) 39 (18.8) 9 (15.5) 0.926

Utility of post-treatment SPECT/CT for identifying disease progression in patients with mCRPC treated with ¹⁷⁷ Lu-PSMA-617.

114 Background: Oncologists have traditionally relied upon serial assessments of PSA and periodic imaging (i.e., every 2 to 3 cycles) to monitor treatment response. Early identification of disease progression allows for faster transitions to alternative therapies that might be more effective. In this study, we evaluated the utility of post-treatment SPECT/CT for earlier detection of treatment failure in patients receiving Lutetium-177–PSMA-617 (LuPSMA). Methods: We queried an IRB-approved registry including all patients starting LuPSMA at Mayo Clinic, MN, in the interval of March 2022 to March 2023. Those receiving fewer than 2 cycles of treatment and missing SPECT/CT data were excluded. We reviewed clinical notes to document the date and reason(s) for treatment discontinuation. The assembled cohort consists of patients stopping LuPSMA for progressive disease ([PD], categorized as biochemical, radiographic, or both). Results of the prior SPECT/CT imaging reports were reviewed. At our institution SPECT/CT images are typically acquired on the day after each infusion. Metrics collected from the radiology reports included: new foci of PSMA localization since the prior PSMA PET or SPECT/CT, suspicion for new non-PSMA avid disease, and a visual determination of PSMA-avid tumor volume. Results: A total of 256 patients received an initial cycle of LuPSMA. SPECT/CT imaging data for at least 2 consecutive treatment cycles was available for 68 patients who developed PD after a median (IQR) of 3 (2-4) cycles. There were 55 patients (81%) with both biochemical and radiographic evidence of PD, 7 (10%) with biochemical only progression, and 6 (9%) with radiographic only progression. The most used imaging modality for response assessment was PSMA PET/CT (n=46, 67%), followed by conventional imaging (n=9, 13%), and choline PET/CT (n=5, 7%). The median time between most recent post-therapy SPECT/CT and determination of PD was 39 days. The prior SPECT/CT had detected new foci of PSMA avid disease in 12 (18%) cases and new non-PSMA avid disease in 5 (7%) cases. Two patients had both new PSMA-avid and non-PSMA avid lesions. The most common sites of new PSMA-avid disease on SPECT/CT were bone (n=10) and liver (n=2). A total of 20 (29%) patients had visually increased tumor volume on SPECT/CT, 9 (45%) of which had no new lesions. In total, 24 of 68 patients (35%) had early detection of treatment futility detected by SPECT/CT. At a median (IQR) follow-up time of 8 (6.4-12) mo, the median OS [95% CI] was similar for patients with PD detected on SPECT/CT (7.8 [6.6 – 9] mo) compared to those without clear evidence of PD on SPECT/CT(8.4 [6.4-10.3] mo, p=0.885). Conclusions: Post-treatment SPECT/CT imaging may complement traditional forms of response assessment and provide an earlier warning of treatment failure through identification of new PSMA-avid lesions, non-PSMA avid disease, and increased tumor volume.