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Patient characteristics and overall survival with lutetium (Lu ¹⁷⁷ ) vipivotide tetraxetan ( ¹⁷⁷ Lu-PSMA-617): A real-world analysis of early adopters.

63 Background: 177 Lu-PSMA-617, a prostate-specific membrane antigen (PSMA)-targeting radioligand therapy for metastatic castration-resistant prostate cancer (mCRPC), received FDA approval in March 2022 for the treatment of adult patients with PSMA-positive mCRPC who have received both an androgen receptor pathway inhibitor (ARPI) and a taxane-based chemotherapy. Outside of clinical trials, limited real-world evidence evaluating the effectiveness of 177 Lu-PSMA-617 has been reported. The aim of the current study was to evaluate patient characteristics and overall survival (OS) among patients diagnosed with mCRPC who were treated with 177 Lu-PSMA-617 within a large-scale real-world cohort. Methods: This retrospective, observational study used the IQVIA PharMetrics Plus claims data from July 1, 2013 to December 31, 2023, and linked social determinants of health data as well as mortality data to obtain month and year of death. Adult men with mCRPC who had received 177 Lu-PSMA-617 were included (first receipt of 177 Lu-PSMA-617 = index date). Patient demographics and characteristics were evaluated descriptively; patient demographics were reported on the index date and clinical characteristics were evaluated over the 12 months prior to index date. OS was measured from the start of the first 177 Lu-PSMA-617 treatment until death or end of available follow-up, and assessed using Kaplan–Meier analysis. Results: A total of 643 patients were included in the analysis; median age was 69 years. Treatment for the majority of patients (490/643 [76.2%]) was managed by oncologists (169 [26.3%] of which had specialty in radiation oncology). White patients (292 [72.8%]) made up the largest part of the patient population followed by Black (37 [9.2%]), Hispanic (23 [5.7%]), and Asian (8 [2.0%]). Most patients had multiple comorbidities with either one (226/643 [35.1%]) or two (224/643 [34.8%]) sites of metastasis. Most patients experienced bone metastases (581/643 [90.4%]); 284/643 (44.2%) also experienced visceral metastases of which the liver was the most common site (78/643 [12.1%]). The median OS from start of 177 Lu-PSMA-617 therapy was 15.3 months (95% confidence interval [CI]: 14.6–16.3); a total of 137/643 (21.3%) patients died. OS was analyzed in different patient subgroups and no major differences were observed by metastatic site, number of metastatic sites, race, or age. Conclusions: To our knowledge, this is the first large-scale study reporting OS with 177 Lu-PSMA-617 in clinical practice. OS observed with 177 Lu-PSMA-617 in this study (median: 15.3 months) was consistent with results from the VISION Phase III clinical trial (median: 15.3 months; NCT03511664). Furthermore, 177 Lu-PSMA-617 demonstrated similar survival across different patient subgroups.

In Silico identification and characterization of SOS gene family in soybean: Potential of calcium in salinity stress mitigation

Leguminous crops are usually sensitive to saline stress during germination and plant growth stages. The Salt Overly Sensitive (SOS) pathway is one of the key signaling pathways involved in salt translocation and tolerance in plants however, it is obscure in soybean. The current study describes the potential of calcium application on the mitigation of salinity stress and its impact on seed germination, morphological, physiological and biochemical attributes of soybean. The seeds from previously reported salt-tolerant and salt-susceptible soybean varieties were primed with water, calcium (10 and 20 mM), and stressed under 60, 80 and 100 mM NaCl and evaluated in various combinations. Results show that germination increased by 7% in calcium primed non-stressed seeds under non-stressing, whereas an improvement of 15%-25% was observed in germination under NaCl stress. Likewise, improvement in seedling length (3%-8%), plant height (9%-18%), number of nodes (3%-14%), SOD activity (20%) and Na+/K+ concentration (3%-5% reduction) in calcium primed plants, indicates alleviation of salinity-induced negative effects. In addition, this study also included in silico identification and confirmation of presence of Arabidopsis thaliana SOS genes orthologs in soybean. The research of amino acid sequences of SOS proteins from Arabidopsis thaliana (AtSOSs) within Glycine max genome displayed protein identity (60–80%) thus these identified homologs were called as GmSOS. Further phylogeny and in silico analyses showed that GmSOS orthologs contain similar gene structures, close evolutionary relationship, and same conserved motifs, reinforcing that GmSOSs belong to SOS family and they share many common features with orthologs from other species thus may perform similar functions. This is the first study that reports role of SOSs in salt-stress mitigation in soybean.

The internet usage increases fear of infection with Covid-19

Outcomes of patients with stage I testicular cancer following orchidectomy with borderline retroperitoneal lymph node enlargement at diagnosis.

633 Background: Approximately 60% of men diagnosed with testicular cancer present with Stage I disease. Most metastases occur in the retroperitoneal lymph nodes (RPLN); RPLN measuring 8-10 mm in the long axis in the appropriate landing zone are considered highly suspicious, and those measuring > 10 mm usually receive additional surgery, chemotherapy or radiation. Many of these patients’ (pt) RPLN will spontaneously regress without additional treatment. Our goal is to better understand the incidence, natural history, and predictors of such spontaneous RP nodal regressions. Methods: We performed a retrospective chart review of clinical records and staging CT imaging reports from all pts followed at Princess Margaret Cancer Centre (PM) from 2004 – 2024 with Stage I-IIA testicular cancer following orchidectomy. Our primary outcome of interest was the 5-year relapse-free survival (RFS, calculated using the Kaplan–Meier method) of pts with testicular cancer with borderline RPLN (longest dimension 8-14 mm based on first CT scan done within 60 days of orchidectomy) in the appropriate landing zone with no other sites of metastases, and declining or normal tumor markers (AFP, HCG and/or LDH) post-orchiectomy who were initially managed with active surveillance according to a pre-determined schedule with additional interim assessments as deemed appropriate by the treating team. Secondary outcomes included identifying histopathologic predictors of relapse in pts who ultimately went on to require further treatment using a Cox proportional-hazards model. Results: Of the 1535 pts with Stage I-IIA disease, 126 had borderline enlarged RPLN (8.2%). 63.7% were pure seminoma (SEM) and 36.3% were non-seminoma germ cell tumors (NSGCT). Incidence of right, left, and bilateral primaries was 47.6%, 50.8% and 1.6% respectively. Median age at consultation was 33 (SEM; range 19-59) vs 27 (NSGCT; range 19-49) years. Median follow-up was 61.9 (5.8 – 203) months. 5-year RFS was 56% (95% CI 46%-64%) in the entire cohort, 61% (95% CI 49%-71%) in SEM and 48.9% (95% CI 33.7%-62.4%) for NSGCT (p = 0.024 SEM vs NSGCT). Median time to relapse (TTR) was 15.8 (95% CI 6.5-25.0) weeks. 5-year OS was 100% regardless of relapse status. Pure embryonal carcinoma (EC) histology (p = 0.014) and LVI (p = 0.03) were associated with subsequent relapse. Rete testes invasion, primary tumor size, largest LN diameter and number of suspicious nodes were not associated with relapse (p > 0.05 for all). Conclusions: It is reasonable to consider careful close interval follow-up and active surveillance in pts with borderline RPLN and falling or negative tumor markers. Short interval follow-up CT scan (6-8 weeks) after orchidectomy to re-evaluate borderline RPLN may spare overtreatment of men who have been cured with orchiectomy alone. EC histology and LVI were independent predictors of relapse.

Impact of tumor burden or focality in recurrent low-grade intermediate-risk non-muscle-invasive bladder cancer on response to treatment with UGN-102: A substudy of the phase 3 ENVISION trial.

776 Background: The ENVISION phase 3 study (NCT05243550) treated patients withlow-grade intermediate-risk non-muscle-invasive bladder cancer (LG-IR-NMIBC) with UGN-102, a reverse thermal hydrogel containing mitomycin. Primary efficacy and safety results were previously reported. Complete response (CR) rate at 3 months was 79.6%, with an 82.3% probability of remaining in response 12 months later by Kaplan-Meier estimate. We conducted a post-hoc analysis to evaluate if certain tumor characteristics influenced response rate and durability. Methods: In the single-arm ENVISION study, 240 patients with LG-IR-NMIBC received at lease one dose of UGN-102, 95% (228) received all 6 weekly doses; 3 months after the first dose, patients were examined for the presence of bladder cancer using cystoscopy, urine cytology testing, and for-cause biopsy. Patients achieving CR (no detectable disease) entered the follow-up period and were surveilled regularly for recurrence. Between group comparisons were performed for CR rate (CRR) at 3 months and duration of response (DOR) 12 months after achieving CR in patients with tumor burden ≤ or >3 cm (calculated as total length of all tumors), and for single vs multiple tumors. Hazard ratios (HRs) of DOR were calculated using a Cox Proportional Hazards (PH) model, and p-values calculated using a log-rank test; p-values for the comparison of CRR were calculated using Fisher’s Exact Test. Results: CRR at 3 months was 82.8% vs 73.2% for patients with tumor burden ≤3 cm and >3 cm, respectively. Of the patients with CR at 3 months, 15.4% vs 20% experienced recurrence of LG disease, progression (either in stage or grade), or death by 15 months. In patients with multiple vs single tumors, 3-month CR was 79.3% vs 82.9%, with recurrence rates of 18.5% vs 11.8%. DOR HRs were not statistically significant for any comparison made (table). Conclusions: Although a non-significant higher event rate was observed at 3 months for patients with a higher tumor burden, the CRR was robust, and the majority of patients remained event free at 15 months. These results demonstrate that chemoablation using UGN-102 results in a high, clinically meaningful CRR in patients with recurrent LG-IR-NMIBC, regardless of tumor burden or multifocality. Study limitations were the small sample size of the comparator groups, single arm design, and post-hoc nature of the analysis. UGN-102 may represent a valuable treatment option for many patients with LG-IR-NMIBC. Clinical trial information: NCT05243550 . CR at 3 months CRR(95% CI) / p value* Recurrence within 15 months DOR HR(95% CI) / p value* Tumor size ≤3 cm>3cm 149/180 (82.8%)30/41 (73.2%) 1.13 (0.93–1.38) / p=0.1854 23/149 (15.4%)6/30 (20.0%) 0.777 (0.317–1.909) / p=0.5816 Tumor count MultipleSingle 157 /198 (79.3%)34/41 (82.9%) 0.96 (0.82 –1.12) / p=0.6740 29/157 (18.5%)4/34 (11.8%) 1.644 (0.578–4.677) / p=0.3459 *Nominal.

Liver Transplantation for Hepatocellular Carcinoma: An Expanding Cornerstone of Care in the Era of Immunotherapy

Liver transplantation (LT) has been accepted as a cornerstone of care in hepatocellular carcinoma (HCC) for almost three decades. In recent years, its role has been evolving to include patients with disease burden beyond the widely used Milan criteria. The integration of dynamic biomarkers such as alpha-fetoprotein together with downstaging approaches and tumor evolution after enlistment has allowed the selection of patients most likely to benefit, resulting in 5-year survival rates greater that 70%. With the increasing use of immune checkpoint inhibitors (ICIs) across all stages of disease, alone or in combination with locoregional therapies, there is now the potential to further expand the patient population with HCC who may benefit from LT. This brings challenges, given the global shortage of organs and the need to better understand the optimal use of ICIs before transplantation. Furthermore, the field of transplant oncology awaits additional biomarkers that can predict those likely to benefit from ICIs. More than ever, a multidisciplinary approach for liver cancer management is critical to ensure all patients are considered for LT where appropriate, and do not miss the opportunity for long-term survival.

Factors influencing sepsis associated thrombocytopenia (SAT): A multicenter retrospective cohort study

Introduction Sepsis associated thrombocytopenia (SAT) is a common complication of sepsis. We designed this study to investigate factors influencing SAT. Methods Patients with sepsis (2984 in Peking union medical college hospital [PUMCH] database, 13165 in eICU Collaborative Research [eICU] database, 11101 in Medical Information Mart for Intensive Care IV [MIMIC-IV] database) were enrolled. Variables included basic information, comorbidities, and organ functions. Multi-variable logistic regression models and artificial neural network model were applied to determine the factors related to SAT. Main results Age and body mass index (BMI) were inversely correlated with the incidence of SAT (p-value 0.175 and 0.049 [PUMCH], p-value 0.000 and 0.000 [eICU], p-value 0.000 and 0.000 [MIMIC-IV]). Hematologic malignancies and other malignancies were positively correlated with the incidence of SAT (p-value 0.000 and 0.000 [PUMCH], p-value 0.000 and 0.000 [eICU], p-value 0.000 and 0.020 [MIMIC-IV]) except other malignancies was inversely correlated with the incidence of SAT in PUMCH database. Norepinephrine (NE) equivalents, total bilirubin (TBIL) and creatinine were positively correlated with the incidence of SAT (p-value 0.000, 0.000 and 0.011 [PUMCH], p-value 0.028, 0.000 and 0.013 [eICU], p-value 0.028, 0.000 and 0.027 [MIMIC-IV]). PaO2 / FiO2 was inversely correlated with the incidence of SAT in PUMCH database (p-value 0.021 [PUMCH]), while it was positively correlated with the incidence of SAT (p-value 0.000 [MIMIC-IV]). PaO2 / FiO2 and SAT was not related (p-value 0.111 [eICU]). TBIL, hematologic malignancies, PaO2 / FiO2 and NE equivalents ranked in the top five significant variables in all three datasets. Conclusions Hematologic malignancies and other malignancies were positively correlated with the incidence of SAT. NE equivalents, TBIL and creatinine were positively correlated with the incidence of SAT. TBIL, hematologic malignancies, PaO2 / FiO2 and NE equivalents ranked in the top significant variables in factors influencing SAT.

Glucagon-like peptide-1 receptor agonists improve metabolic dysfunction-associated steatotic liver disease outcomes

Immune and inflammatory profiling in bladder cancer: Insights into biomarkers and therapeutic strategies.

861 Background: This study aimed to characterize and compare the profiles of inflammatory and immune responses (IFN-γ, CX3CR1, iNOS, PD-L1, CTLA-4, CD163, FOXP3), monoamine oxidases (MAO-A and MAO-B), and the expression of HABP4 (hyaluronan-binding protein 4) and SERBP1 (Serpine1 mRNA-binding protein 1) in bladder tissue samples from patients with initial non-muscle-invasive bladder cancer (NMIBC), BCG-unresponsive NMIBC, and muscle-invasive bladder cancer (MIBC). Additionally, we aimed to provide an overview of the involvement of these factors and their signaling pathways in the tumor microenvironment (TME) of bladder cancer (BC). Methods: A total of 60 formalin-fixed, paraffin-embedded bladder cancer samples were obtained from patients diagnosed with BC at the Paulínia Municipal Hospital and São Vicente de Paulo Charity Hospital, Brazil. The samples were classified into three groups (n= 20 samples per group): Group 1 – initial NMIBC, Group 2 – BCG-unresponsive NMIBC, and Group 3 – MIBC. Immunohistochemical analysis was performed to evaluate the expression of target markers. Results: MAO-A immunoreactivity was significantly elevated (p<0.05) in Groups 1 and 2 compared to Group 3. In contrast, MAO-B expression was significantly higher (p<0.05) in Groups 2 and 3 compared to Group 1. These findings suggest that MAO-A serves as a potential biomarker for superficial disease, whereas MAO-B may be associated with disease progression. Elevated levels of CTLA-4 and PD-L1 were observed in Group 1 relative to Groups 2 and 3 (p<0.05), indicating that BCG treatment reduces their immunoreactivity in both BCG-unresponsive NMIBC and MIBC phenotypes, thereby modulating the TME. Additionally, immunoreactivities of CD163 and FOXP3 were significantly increased (p<0.05) in Group 2, followed by Group 3, implying that FOXP3 + regulatory T cells and CD163 + M2 macrophages contribute to BCG treatment failure and tumor progression. Conversely, IFN-γ, CX3CR1, and iNOS expression were significantly elevated (p<0.05) in Group 1, indicating that a heightened infiltration of CX3CR1 + cells and iNOS + M1 macrophages creates a cytotoxic microenvironment more responsive to immunotherapeutic interventions. This study represents the first report of HABP4 and SERBP1 immunoreactivities in BC. SERBP1 expression was significantly higher (p<0.05) in Groups 2 and 3, linking its overexpression to tumor progression. In contrast, HABP4 expression was significantly elevated (p<0.05) in Group 1 compared to Groups 2 and 3, supporting its role in inhibiting cell proliferation. Conclusions: These findings suggest that analyzing markers such as MAO-A, MAO-B, HABP4, and SERBP1 can improve risk stratification, prognosis, and personalized therapies for BC patients, particularly in the context of immunotherapies. Identifying specific profiles in the TME can guide more effective, tailored treatments and enhance clinical outcomes.

The evaluation of therapeutic outcomes of percutaneous US/CT-guided bipolar radiofrequency ablation for small renal masses under local anesthesia.

556 Background: This study is to evaluate the safety and feasibility of local anesthesia (LA) for percutaneous ultrasound/computed tomography (US/CT)-guided bipolar radiofrequency ablation (RFA) for small renal masses (SRMs) by comparing the LA with general anesthesia. Methods: A retrospective review was carried out between 2018 to 2023, 212 patients with SRMs were treated with US/CT-guided bipolar RFA. General anesthesia (GA) was performed in 91 and LA was performed in 121 patients. Demographics, tumor characteristics, peri-procedural data, pathologic and follow-up outcomes were analyzed. The factors associated with pain were also identified. Results: There was no significant difference in demographics and tumor characteristics between the LA and GA group. Several statistically significant decrease were observed in terms of procedural time ( P <0.001), hospital stays ( P <0.001) and hospital costs ( P <0.001). The maximum perceived pain in LA group comprised 57.9% (70 of 121) mild, 42.1% (51 of 121) moderate. The anxiety in LA group comprised 62.0% (75 of 121) mild, 36.3% (44 of 121) moderate, 1.7% (2 of 121) severe. On multivariate analysis, tumor diameter was a significant predictor for pain in RFA procedure (OR 1.470, P <0.001). All patients were followed up for a median (range) of 36 (12-48) months. Local recurrence occurred in 15.7% (19 of 121) of the LA group and in 13.2% (12 of 91) in GA group ( P =1.000). Moreover, there was no significant difference in the difference between postoperative eGFR and preoperative eGFR when comparing the two groups. Conclusions: Percutaneous bipolar RFA of SRMs using CT and ultrasound guidance under LA can be an effective and tolerable method for patients who are unfit for surgery and provide satisfactory oncologic control.

CD39 expression as a predictive biomarker for neoadjuvant treatment in muscle-invasive bladder cancer.

850 Background: Neoadjuvant therapy before radical cystectomy (RC) is the the standard treatment for muscle-invasive bladder cancer (MIBC). However, a significant number of patients do not respond to these therapies. Identifying biomarkers predictive of treatment response and developing novel therapeutic strategies are crucial to improving patient management and survival. This study aims to investigate non-invasive biomarkers that can predict response to neoadjuvant therapy in MIBC patients and explore their potential use in the design of new therapies. Methods: Immunophenotyping was performed on blood and bladder tissue samples from MIBC patients at pre-treatment (transurethral tumor resection (TUR); n=17; chemotherapy n=13 and immunotherapy n=4) and post-neoadjuvant treatment (RC, n=21; chemotherapy n=18 and immunotherapy n=3). Plasma soluble CD39 (sCD39) and adenosine levels were measured by ELISA and an enzymatic assay, respectively. Treatment response was evaluated at RC, and patients were classified as non responders (³ypT2³N1) or responders (<ypT2ypN0). Results: Non responder patients exhibited a significant higher percentage of CD39 + cells in circulating total and different maturation CD4 + T cells subsets, particularly at TUR, suggesting a potential role in treatment resistance. CD39 + CD4 + T cells showed elevated PD-1 expression, decreased levels of Granzyme-B and Perforin, and strong correlations with the regulatory T cell marker FoxP3 and the checkpoint inhibitor TIGIT. Intratumoral CD39 + CD4 + T cells were also more frequent in non responder patients, correlating positively with the expression of tumor checkpoint inhibitors TIGIT and ICOS and the regulatory marker FoxP3. In blood, CD39 + CD4 + T cell frequencies correlated with sCD39 levels, which in turn were associated with adenosine concentration in plasma. Conclusions: CD39 expression in CD4 + T cells and its plasma levels emerge as promising biomarkers for predicting response to neoadjuvant treatment in MIBC. Targeting CD39 may offer a novel therapeutic strategy to overcome treatment resistance, potentially improving outcomes in MIBC patients.

Type 1 diabetes incidence during COVID-19 pandemic has not been influenced by COVID-19 vaccination in northern Italy region, Lombardy

Objective To describe the trends of type 1 diabetes(T1D) incidence in 0–17-year-olds over the years 2020–2023, and the COVID-19 vaccination uptake in Lombardy region. Methods Data about children and adolescents aged 0–17 years who received a diagnosis of T1D from 2020 to 2023 were extracted from the public computerized registry of the healthcare system of the Lombardy Region (Italy). After calculating the annual T1D incidence, the incidence in 2020, prior to the availability of vaccination, was compared to subsequent years. A separate analysis was conducted for the 12–17 age group, the first to receive vaccination. Results One thousand two hundred seventy-three T1D onsets were recorded. The distribution of T1D showed no significant annual variation by sex (p-trend = 0.338), mean age (9 years, p = 0.537) and age distribution (p-trend = 0.563). T1D incidence [95% CI/100.000] did not significantly change comparing 2020 [18.94/100.000 (CI 16.88–21.18)] with 2021 [21.82/100.000 (CI 18.90–23.44)], 2022 [20.77/100.000 (CI 18.59–23.13)] and 2023 [19.68/100.000 (CI 16.61–20.94)]. No differences in incidence were observed in the 12–17 age group during 2021–2023 when COVID-19 vaccination was available when compared to 2020 (p-wald > 0.05). The COVID-19 vaccination coverage was lower in children with diabetes onset compared to the same-age general population (38 vs 42%). Conclusions The incidence of T1D in children remained stable during the COVID-19 pandemic, regardless of the uptake of the vaccination.

Lifespan in rodents with MYT1L heterozygous mutation

CLARIFY: Positron emission tomography using ⁶⁴ Cu-SAR-bisPSMA in patients with high-risk prostate cancer prior to radical prostatectomy—A phase 3 diagnostic performance study.

TPS429 Background: Prostate cancer (PC) is the second most prevalent cancer in men globally. In men with newly diagnosed, high-risk disease, PC most often spreads to the pelvic lymph nodes (LNs) before becoming widely metastatic. Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein that is strongly overexpressed in PC, making it an ideal target for imaging and therapy. 64 Cu-SAR-bisPSMA may offer several advantages over the currently approved PSMA positron emission tomography (PET) agents due to its bivalent structure (SAR-bisPSMA) and longer half-life of 64 Cu (12.7h vs. <2h for 18 F and 68 Ga). 64 Cu-SAR-bisPSMA has demonstrated higher tumor uptake (2-3x), prolonged retention and detection of additional PC lesions compared to approved PSMA agents. This Phase 3 diagnostic trial aims to establish the diagnostic performance of 64 Cu-SAR-bisPSMA PET to detect regional nodal metastases in men with high-risk PC. Methods: CLARIFY (NCT06056830) is a multi-center, single-arm, non-randomized, open-label Phase 3 diagnostic study of 64 Cu-SAR-bisPSMA. The target population is patients with untreated, histopathology-confirmed PC with high-risk features, who are proceeding to radical prostatectomy (RP) with pelvic lymph node dissection (PLND). The primary endpoint is to assess the sensitivity and specificity of 64 Cu-SAR-bisPSMA PET to detect pelvic nodal metastases. Secondary objectives include assessment of safety and determining the positive and negative predictive value of 64 Cu-SAR-bisPSMA PET. A total of 383 patients will be enrolled. Standard of care (SOC) imaging will be acquired at screening (e.g. computed tomography [CT], approved PSMA PET/CT). Eligible patients will receive a single administration of 64 Cu-SAR-bisPSMA (200 MBq) followed by a PET/CT scan on Day 1 (1-4h post-dose, same-day imaging) and on Day 2 (24±6h post-dose, next-day imaging). Patients will then proceed to RP with PLND. The specimens from surgery will be processed and analyzed locally to derive the Standard of Truth (SOT). The 64 Cu-SAR-bisPSMA PET/CT scans will be interpreted locally and by 3 independent, blinded, central readers. Each reader will assess the scans for the presence of abnormal 64 Cu-SAR-bisPSMA uptake in the pelvic LNs, prostate gland, extra-pelvic LNs, visceral/soft tissue and bone. The diagnostic performance of 64 Cu-SAR-bisPSMA will be based on the PET result on the respective day independently (Day 1 and 2) matched against the SOT. The study is open for recruitment in sites in the United States and in Australia. Clinical trial information: NCT06056830 .

Neoadjuvant darolutamide and relugolix combination preceding radical prostatectomy for high risk localized and locally advanced prostate cancer: A phase I/Ib trial.

TPS433 Background: Intensive androgen blockade with combination novel hormonal agent (NHA) + androgen deprivation therapy (ADT) appears promising as neoadjuvant therapy for high-risk localized prostate cancer (PCa) undergoing radical prostatectomy (RP). An all-oral regimen combining relugolix and darolutamide may be feasible, convenient, efficacious and exhibit no significant drug-drug interactions as neoadjuvant therapy for high-risk localized PCa and may convert patients who were initially inoperable to operable. Additionally, the rapid reversibility of castration will allow the reliable determination of post-operative PSA nadir to inform tailored adjuvant therapy. Moreover, given the convenience, this regimen may constitute an excellent backbone to develop additional combinations in future. Hence, a rationale may be made to evaluate the combination of relugolix and darolutamide as neoadjuvant therapy for 12 weeks preceding RP for high-risk localized/locally advanced PCa. Methods: This is a Phase I/Ib non-randomized, uncontrolled, open-label clinical trial evaluating the primary objective of safety and feasibility of combination darolutamide (600 mg PO BID) and relugolix (360 mg on day 1, then 120 mg PO once daily) for 12 weeks as neoadjuvant therapy preceding RP which is to be performed ≥48 hours after and within 2 weeks after completion of neoadjuvant therapy. Patients included in this study must be a candidate for RP with stage cT2-4, N0-1, high risk (defined as Gleason score (GS) ≥ 4 + 3 with ≥ 6 positive systematic biopsies (SB); GS ≥ 4 + 3 with ≥ 3 SB and prostate-specific antigen (PSA) ≥ 20 ng/mL; GS ≥ 9 in ≥ 1 SB or targeted biopsies (TB); or ≥ 2 SB or TB with continuous GS ≥ 8, each with ≥ 80% involvement), histologically or cytologically confirmed adenocarcinoma of the prostate. The Phase I component will accrue 10 patients. If ≥7 patients complete neoadjuvant combination therapy followed by RP with no severe therapy-related adverse events for up to 4 weeks following RP, the regimen is considered feasible and accrual of 20 additional patients continues in the Phase Ib expansion component of the trial to achieve a total of 30 patients. Secondary objectives include clinical response, pathologic complete response with comparison with control matched untreated group that underwent upfront RP, rate of achieving undetectable PSA nadir and testosterone recovery to normal within 8 weeks after RP and post-operative complications. Pharmacokinetic studies are performed in the Phase I component. Blood, tumor and urine are stored for future correlative studies. The trial was activated in October 2024. Clinical trial information: NCT06631521 .

Assessing the clinical impact of tumor volume on response to ¹⁷⁷ Lu-PSMA radioligand therapy in metastatic castration-resistant prostate cancer.

175 Background: 177 Lu-PSMA-617, a PSMA-directed radionuclide therapy, is an emerging treatment for metastatic castration-resistant prostate cancer (mCRPC). This retrospective study evaluates clinical outcomes of 177 Lu-PSMA-617 in low volume (LV) and high volume (HV) mCRPC, classified using the CHAARTED criteria. Methods: We conducted a retrospective review of the Mayo Clinic Prostate Cancer Registry, including mCRPC patients treated with 177 Lu-PSMA-617 at Mayo Clinic Rochester, MN, from August 2017 to August 2024. Patients were categorized based on CHAARTED criteria, which define high-volume disease by the presence of visceral metastases and/or four or more bone metastases, with at least one outside the vertebral column and pelvis. PSA-response rate (PSA-RR), overall survival (OS), PSA-progression-free survival (PSA-PFS), and radiographic progression-free survival (rPFS) were analyzed using Kaplan-Meier curves with log-rank tests, as well as uni- and multivariate Cox regression. Results: Of the 264 patients treated with 177 Lu-PSMA-617, 83 were classified as LV (median follow-up: 17.1 months) and 177 as HV (median follow-up: 13.7 months). LV patients had lower serum PSA levels (P < 0.0001), higher hemoglobin levels (P < 0.0001), and a longer time from diagnosis to treatment initiation (10.3 years vs. 7.2 years, P = 0.04). In the HV group, 92% had bone metastases, 60% had lymph node involvement, 54% had both, and 35% had visceral metastases. In the LV group, 64% had bone metastases, 84% had lymph node involvement, 25% had both, and none had visceral metastases. Median OS was 14.4 months for HV patients and 17.6 months for LV patients (P < 0.0001). Median PSA-PFS was 11.4 months for HV patients and 13 months for LV patients. Median rPFS was 9.1 months for HV patients and 10.6 months for LV patients. PSA-RR significantly differed between groups (P < 0.0001). In the HV group, 20% achieved CR (PSA < 0.2 ng/mL), 29% had PR (PSA decreased by ≥50%), 16% experienced SD, and 35% had PD (PSA increased ≥25% from nadir). In contrast, the LV group had 51% achieving CR, 10% achieving PR, 18% with SD, and 11% with PD. Conclusions: Lower disease volume in mCRPC is strongly associated with improved outcomes following 177 Lu-PSMA-617 therapy. These findings suggest that tumor burden is a key predictor of response to PSMA radioligand therapy.

Correction: A peripheral subepithelial network for chemotactile processing in the predatory sea slug Pleurobranchaea californica

Circulating lncRNA HOTAIR is a biomarker for pediatric acute lymphoblastic leukemia and mediator of miR-326 exosomal export

Impact of androgen deprivation therapy with postoperative radiotherapy after radical prostatectomy on health-related quality of life.

133 Background: There is an ongoing debate on the use and duration of androgen deprivation therapy (ADT) with postoperative radiotherapy (RT) following radical prostatectomy (RP). While there have been conflicting results regarding oncological outcome, the effect of concomitant ADT on health-related quality of life (HRQOL) remains elusive. We aimed to assess the impact of adding ADT to postoperative RT on long-term HRQOL by providing PROM data from a large contemporary cohort of patients undergoing RT following RP with a systematic follow-up of up to 10 yrs. Methods: n=1124 patients who underwent RT after previous RP at a large tertiary care center between 2010 and 2021 were identified within a prospective institutional database. Patients with previous post-op ADT were excluded. Patients were stratified by concomitant ADT (no ADT n=682; ADT n=436). PROMs were prospectively assessed preoperatively, prior and post RT and at a maximum follow-up of up to 120mo, applying the validated EORTC QLQ-C30- and the prostate cancer-specific QLQ-PR25-questionnaires. Correlation analysis and multivariable regression models were used to estimate the impact of ADT with postoperative RT on HRQOL. Results: Median duration of ADT received within the ADT-cohort was 21mo. Prior RT, no significant difference in general HRQOL assessed by the global health status domain (GHS) was found between the ADT cohort (69.6) and the no ADT cohort (68.9; p=0.88). Post RT (65.1 vs. 69.9; p=0.038) and after median follow-up of 59 months (62.8 vs. 68.1; p<0.001) patients in the ADT cohort reported significantly worse general HRQOL. In multivariable regression analysis stratified by age, BMI, pT-stage, urinary continence and erectile functioning, concomitant ADT was confirmed as an independent predictor for worse general HRQOL (OR 0.68, 95% CI 0.47-0.96, p=0.03). Correlation analysis revealed a significant correlation between longer duration of ADT and worse long-term general HRQOL (p<0.001). In line, multivariable linear regression analysis revealed longer duration of ADT to independently predict worse general HRQOL (p=0.041) (Table). Conclusions: In patients with postoperative RT, concomitant ADT yields worse long-term general HRQOL. A longer duration of ADT furthermore leads to worse long-term general HRQOL. Those results support careful patient selection for ADT with postoperative RT after RP. Multivariable linear regression for HRQOL. Variable B [regression coefficient] Beta [standardized regression coefficient] SE [standard error] p value Duration of ADT -0.272 -0.191 0.132 0.041 Age -0.127 -0.043 0.294 0.667 BMI -0.588 -0.120 0.444 0.188 ICIQ-SF-Score 0.914 0.012 6.729 0.892 IIEF5-Score 0.661 0.165 0.403 0.103 R² 0.341 Adjusted R² 0.336

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

452 Background: Ethnic and racial disparities in oncology clinical trial participation remain a pressing challenge. Despite initiatives by the NCI and FDA since 2017 aimed at addressing these disparities, significant gaps persist in cancer treatment access and clinical trial involvement for minority populations. Notably, data on minority participation in clinical trials for FDA-approved renal cell carcinoma treatments during the post-COVID-19 era is limited. Methods: From 2020 to 2024, we analyzed data from 2,940 patients enrolled in five clinical trials (CheckMate 9ER, CLEAR, KEYNOTE 564, LITESPARK 005, TIVO-3) that resulted in FDA approval of new agents or indications for renal cell carcinoma. All trials were industry-sponsored. We assessed and tabulated the reporting of racial demographics within these trials, employing chi-square statistics and machine learning algorithms to compared participation rates among White, Black, Asian and Hispanic patients against SEER data on renal cell carcinoma incidence. Results: Among the five trials, three (KEYNOTE 564, LITESPARK-005, and TIVO-3) reported racial data, but only two (KEYNOTE 564 and LITESPARK-005) provided information beyond White participants, including Black and Asian populations. No data on Hispanic participation was reported. Our analysis revealed that in the three trails providing racial data, 88% of participants were White indicating statically significant overrepresentation (p<0.0001). In the two trials with broader racial data, Black participation was only 1.2% signifying substantial underrepresentation (p<0.0001), while Asian representation was 11.6% with no significant disparity observed (p=0.05). Conclusions: The underrepresentation of minority groups (particularly Blacks and Hispanics) in FDA-approved clinical trials for renal cell carcinoma remains a significant concern in the post-COVID-19 landscape. Addressing these disparities necessitated the implementation of policies that enhance data collection and standardize ethnic classification. Additionally, international collaborative trials should prioritize distinct data reporting for U.S. participants, utilizing NCI SEER nomenclature for consistency.