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Background The pathophysiology of CS is complex and is associated with increased inflammation and impaired vascular tone. Corticosteroids are recommended in septic shock and have been proposed as a potential treatment for other types of shock. Objectives We sought to evaluate the clinical outcomes associated with early corticosteroid use in patients with cardiogenic shock (CS). Methods Using a nationally representative database including over 1000 hospitals, we identified adults ≥18 years of age admitted from 2015–2023 with a diagnosis of CS. Patients with adrenal insufficiency, chronic rheumatologic conditions, COVID-19 infection and acute COPD exacerbation were excluded. Using inverse probability treatment weighting (IPTW), we assessed for the association of receiving early corticosteroids (within the first 2 days of admission) versus no early corticosteroids and in-hospital mortality. Results Of the 167,721 identified patients with CS, the mean (SD) age was 65.5 (±15.2) years and 35.0% were women. A total of 13.2% received any corticosteroid within the first 2 days of admission. The most common corticosteroid was hydrocortisone (73.9%). Mortality for those receiving and not receiving early corticosteroids was 48.8% and 29.6% ( p < 0.001), respectively. After IPTW, early corticosteroid use remained associated with a 3.1% (95% confidence interval [CI]: 2.4% to 3.8%, p < 0.001) higher mortality. Among patients with CS and concomitant sepsis, 27.6% received early corticosteroids, which was similarly associated with a higher mortality (weighted mean 5.8% [95% CI: 4.6% to 7.0%, p < 0.001]). Conclusions Approximately 1 in 7 patients with CS received corticosteroids early during their admission, which was associated with higher in-hospital mortality.

Objective The United Nations defines sustainability as meeting needs of the present without compromising future generations. While often equated to “saving the planet”, sustainability is a diverse topic. Healthcare generates &gt;5% of CO 2 emissions worldwide, yet sustainability efforts in urology are limited. The North Central Section of the American Urological Association (NCSAUA) recently convened a Sustainability Task Force to address this topic. This study queried members on sustainability in urologic practice. Methods Following literature review on sustainability in surgery/urology, a 19-item anonymous REDCap survey was developed and distributed via email to NCSAUA members (N = 1607). The survey assessed current best practice, institutional/personal sustainability, and demographics. Responses were compiled and summarized using descriptive statistics. Results Survey response rate was 4.9% (79/1607). Respondents were most commonly from metropolitan areas (82%), male (71%), and in practice for 5–14 years (29%). Sustainability topics were prioritized as: (1) financial, (2) future workforce, (3) environmental. Over half (56%) reported no institutional sustainability programs or were unaware of them. Instrument (67%), computer (68%), and paper (65%) recycling were supported by a majority of respondents. However, only 28% and 29% of respondents reported current institutional use of instrument and computer recycling, respectively. Telemedicine was infrequent, with most urologists (58%) conducting 0-5% of visits virtually. Conclusions Current institutional and urologic practice emphasis on sustainability is low. Respondents ranked highest sustainability priorities as financial and future workforce. Efforts to address environmental sustainability were also supported, namely reduction of disposables and waste. The findings support the development of targeted programs to advance sustainability priorities widely.

Background: There is growing support for high-efficacy disease-modifying therapy (DMT) in multiple sclerosis (MS), but escalation (ESC) approaches remain common. Objective: To describe decision-making in a pragmatic trial of early high-efficacy treatment (EHT) versus ESC. Methods: DELIVER-MS is a multi-center, pragmatic, randomized controlled trial (RCT) with a parallel observational study (OBS), which enrolled treatment-naïve people with RRMS in 31 UK/US sites. Primary outcome was as follows: 36-month brain volume loss according to initial treatment approach (EHT vs. ESC). Stepwise multivariable logistic regression was used to predict participation in RCT versus OBS and choice of EHT versus ESC within the OBS cohort. Results: In total, 816 people with MS were enrolled. Participants declined randomization due to preference for a particular DMT (85%), efficacy concerns (20%), and safety concerns (9%). RCT versus OBS participation was associated with lower relapse rate ( p = 0.043) and greater brain parenchymal fraction ( p = 0.002). Among 374 in the OBS cohort, 125 (33%) chose ESC and 249 (67%) chose EHT. People commencing EHT had higher education attainment ( p < 0.001) and relapse rate ( p = 0.025). Conclusion: Baseline DELIVER-MS data demonstrate that participants with milder disease are more likely to participate in RCT. The choice of EHT versus ESC was associated with demographic factors and disease activity. Clinical trial registration: NCT03535298

Abstract Repetitive head impacts sustained during American football have been associated with neuropathological changes such as white matter shear injuries. However, the impact of specific factors, such as age of first exposure and cumulative head impact burden, on white matter integrity remains unclear. This study investigated in vivo white matter microstructural changes using diffusion tensor imaging and tract-based spatial statistics in 165 male former American football players (mean age 57.3 years, range 45–74) and 52 unexposed asymptomatic male controls (mean age 59.4 years, range 45–74) in the DIAGNOSE CTE Research Project. Compared to controls, former football players exhibited significantly higher fractional anisotropy (FA) in 1.97% of the white matter skeleton (1552 voxels; Cohen’s d = 0.587) and higher tissue-corrected FA (FAt) in 1.48% of the white matter skeleton (1004 voxels; Cohen’s d = 0.616). No significant differences were observed for mean diffusivity, axial diffusivity, radial diffusivity, or free water between football players and controls. Among football players, there were no significant differences in the white matter microstructure between players diagnosed with traumatic encephalopathy syndrome and those without the diagnosis. Lower FA was significantly associated with older age (P &lt; 0.00001) and an earlier age of first exposure to tackle football (P &lt; 0.01), while lower FAt was associated with greater cumulative head impact burden, specifically higher linear acceleration (P &lt; 0.04) and rotational force (P &lt; 0.02). This study highlights the influential role of exposure factors on white matter microstructure in former American football players, as well as the utility of diffusion tensor imaging to aid in characterizing the long-term effects of repetitive head impacts in contact sport athletes.

TPS2103 Background: Treatment for newly diagnosed IDH-mutant astrocytoma, WHO grade 3, is based on the results of the CATNON study, demonstrating benefit of radiotherapy followed by 12 months of adjuvant temozolomide. While temozolomide and radiotherapy significantly improved survival, the prognosis for these patients remains limited and more effective therapies are required. This trial will evaluate the benefit of the addition of the IDH1 and IDH-2 inhibitor vorasidenib to adjuvant temozolomide versus placebo following standard radiotherapy to evaluate possible improvement in outcomes. Methods: Alliance A072301 (NCT07215910) is a multicenter, double-blinded phase 3 randomized study to determine if the addition of vorasidenib to adjuvant temozolomide significantly improves progression-free survival (PFS), based on blinded central review in patients with newly diagnosed, IDH-mutant astrocytoma, WHO grade 3. Key inclusion criteria include age ≥ 12 years old, histological confirmation of astrocytoma (absence of 1p/19q codeletion), WHO grade 3, presence of any IDH mutation, plan for radiation and chemotherapy and surgery within 6 months. The presence of CDKN2A/B homozygous deletion, spinal or leptomeningeal disease, as well as prior chemotherapy, cranial irradiation or IDH inhibitor therapy, is exclusionary. 408 patients will be randomized 1:1 to receive vorasidenib 40 mg or placebo daily with 12 cycles of temozolomide following radiotherapy and then continued as monotherapy until disease progression or unacceptable toxicity. Stratification factors include age (< 40 years old vs ≥ 40 years old) and residual disease (< 2 cm vs ≥ 2 cm). Tumor assessments with MRI will be every three months for the first two years, every four months for the next two years and then every six months thereafter as per blinded independent central review using the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. Key secondary endpoints include PFS by local review, time to next treatment, safety and tolerability, quality of life measures. Exploratory measures will include seizure frequency. The trial will have 85% power to detect a hazard ratio of 0.625 with one-sided type I error rate of 0.025. Enrollment for the trial commenced February 2026. Support: U10CA180821, U10CA180882, U24CA196171. https://acknowledgments.alliancefound.org.

9557 Background: High-dose interleukin-2 (IL-2) is administered following tumor-infiltrating lymphocyte (TIL) therapy, yet cardiotoxicity frequently limits dose delivery. The clinical significance of peri-dose troponin elevations during IL-2 remains poorly defined. We evaluated troponin kinetics during IL-2 dosing and their association with significant cardiac events and IL-2 interruption. Methods: We retrospectively analyzed patients with metastatic melanoma treated with TIL therapy followed by inpatient high-dose IL-2 at Mayo Clinic Rochester (N = 24; 87 IL-2 doses). High-sensitivity troponin and ECGs were obtained before and after each IL-2 dose. Clinically significant cardiac events were defined as QTc prolongation > 480 ms, arrhythmias (excluding isolated sinus tachycardia), new ECG abnormalities, vasopressor requirement, or cardiology consultation. Dose-level outcomes included cardiac events and subsequent IL-2 dose interruption. Paired troponin changes were assessed using Wilcoxon signed-rank testing. Dose-level associations were evaluated using clustered logistic regression to account for repeated IL-2 doses within patients. Results: 24 patients received 87 IL-2 doses (median 3 [IQR 2 - 5]). Median age was 63 years (IQR 54 - 70), and 58% were male. Baseline troponin median was 11 ng/L (IQR 6 - 21); 38% had baseline troponin > 14 ng/L. Post-dose troponin exceeded 14 ng/L in 16/24 patients (67%) and 48/87 doses (52%). Median delta troponin was 0 ng/L (IQR −1 to 6; range −24 to 133), with post-dose levels higher than pre-dose values ( p = 0.02). Clinically significant cardiac events occurred in 33% of patients; no post-IL-2 reductions in left ventricular ejection fraction were observed. At the dose level, cardiac events occurred only when post-dose troponin exceeded 14 ng/L (15/48 [31%] vs 0/39 doses; p < 0.001). In clustered logistic regression, post-dose troponin ≥15 ng/L was independently associated with cardiac events (OR 9.6, 95% CI 1.5 - 60.6; p = 0.02) and subsequent IL-2 dose interruption (OR 3.4, 95% CI 1.1 - 10.7; p = 0.04). When modeled continuously, each 1-unit increase in log-transformed post-dose troponin was associated with higher odds of cardiac events (OR 3.3, 95% CI 1.6 - 6.7; p = 0.001) and IL-2 interruption (OR 2.8, 95% CI 1.6 - 4.9; p < 0.001). Baseline troponin correlated with peak post-dose troponin (ρ = 0.44, p = 0.04). Conclusions: Peri-dose troponin elevations are common during post-TIL high-dose IL-2; however, higher post-dose troponin independently identifies clinically significant cardiac toxicity and predicts IL-2 interruption after accounting for repeated dosing within patients. Baseline troponin modestly predicts peak elevations, supporting standardized, risk-stratified troponin monitoring and prospective evaluation of toxicity-adaptive IL-2 delivery strategies in TIL therapy.

9007 Background: Since transition to virtual interviews, application and interview inflation have increased the work burden of GME recruitment. In 2021, AAMC ERAS implemented a process that allows applicants to assign signals to top programs of interest. There is a paucity of guidance on optimal use of ERAS signals (ES), resulting in apprehension and uncertainty amongst applicants and program directors (PD). For the 2026 ERAS cycle, Hematology/Oncology programs (HOP) had the option to participate in ES, in which applicants are provided 5 gold (G) signals and 15 silver (S) signals. First-hand knowledge on how ES was utilized by HOP, as well as PD perceptions about ES, may guide best practices on ES. Methods: During the ASCO Oncology Training Program Leadership Retreat in November 2025, an anonymous survey, assessing HOP utilization and perception of ES, and the impact of ES on recruitment practices, was launched. One PD from each HOP was invited to complete the survey while onsite. Results: 88 HOP (46% of ACGME HOP) are represented. 97% (n=85) utilized ES. Of HOP who used ES, 74% are academic. 32% are small (1-9 fellows), 43% medium (10-19 fellows), and 25% large (20+ fellows). 79% received 400+ applications. 69% reviewed applications without signals but gave higher consideration to signaled applicants. 25% only reviewed applications with signals. 28% used ES when creating rank list; 45% think ES utilization is appropriate during ranking. 85% reported ES did not alter their approach to applicants requiring visa sponsorship. 78% felt ES made the interview selection process easier. 66% were more satisfied with this year’s recruitment process compared to years without ES. The most requested change to ES was reduction of allowed signals, especially silver. 98% will use ES next year. Conclusions: Despite limited knowledge on ES impact on recruitment, nearly all surveyed HOP participated in ES this past year and will continue. Most HOP view ES positively though many desire changes, particularly with the number of signals. Most HOP consider all applications regardless of ES. However, some HOP with larger applicant pool are using ES as inclusion criteria for interview consideration. Signals are a strong predictor for interview invitation when internal selection criteria are met. The “borderline” applicant may be the greatest benefactor from ES, viewed similarly to the non-signaled applicant who meets internal selection criteria. Sharing PD perspectives and real-life data from this year’s ES process breeds opportunities for further improvement and increased confidence with ES. Likelihood HOP offer interview invitation based on quality of application and signals (%, n=85). Internal Selection Criteria Signal Extremely Likely Likely Neutral Unlikely Extremely Unlikely Met G 73 22 5 0 0 S 42 47 8 2 1 None 8 27 24 22 19 Nearly met G 4 35 39 19 3 S 0 9 52 28 11 Not met G 0 2 12 41 45 S 1 1 6 30 62

603 Background: Accurate prediction of pathologic complete response (pCR) after preoperative therapy for HER2-positive (HER2+) breast cancer can help triage patients to immediate surgery vs additional preoperative therapy. Pre-surgery (i.e., after neoadjuvant therapy) imaging studies may help estimate the likelihood of pCR. In EA1181, patients (pts) with stage II-IIIA HER2+ breast cancer received four cycles of preoperative taxane, trastuzumab, and pertuzumab (THP×4). Pre-surgery imaging was required, though the specific imaging modality was not mandated. Here, we report the accuracy of pre-surgery breast MRI to predict pCR (ypT0/Tis, ypN0). Methods: Among 2,141 pts treated with THPx4, 1,378 had pre-surgery breast MRI and were representative of the overall cohort, although T3 tumors were more common (16% vs 9%). MRI reports were available for 1,351 pts; all reports were centrally reviewed and classified as radiologic complete response (rCR; no residual tumor enhancement and normalization of lymph nodes, if applicable) or radiologic residual disease (rRD). Reports with indeterminate radiologic response were independently reviewed by two study radiologists blinded to pathology outcomes. Among pts with rCR who had pathologic residual disease (pRD), we also assessed the extent of residual disease by residual cancer burden (RCB) score. Among pts with rRD who had a pCR, we determined the proportion who only had residual ductal carcinoma in situ (DCIS). Results: See Table. Conclusions: After neoadjuvant therapy, preoperative MRI accurately predicted pCR in 86% of patients with HER2+/ER− disease and may help identify patients who can proceed directly to surgery. MRI is insufficient to predict pCR for pts with HER2+/ER+ disease, as only 55% with complete response on MRI had a pCR at surgery. A pre-surgery MRI that indicated residual disease was accurate in 80% of pts with HER2+/ER+ disease, but in only 45% of pts with HER2+/ER- cancer. Accurately predicting residual disease after THPx4 allows for consideration of additional therapy that may increase the chance of pCR. Combining imaging like MRI with other biomarkers, such as tissue-based markers or circulating tumor DNA, may improve prediction of pCR and facilitate personalization of treatment decisions in HER2+ breast cancer. All pts with pre-surgery MRI (n=1351)pCR rate overall in this cohort = 47% MRI result Pathology pCR pRD rCR 70.6% (341/483) 29.4%(142/483) 78% had RCB1 rRD 34%(295/868) 21% of 295 had DCIS only 66.01% (573/868) ER- (n=589)*Overall pCR rate in ER- subset = 68% MRI result Pathology pCR pRD rCR 86.1% (205/238) 13.9% (33/238) 85% had RCB1 rRD 55.3% (194/351) 19% of 194 had only DCIS 44.7% (157/351) ER+ (n= 762)*Overall pCR rate in ER+ subset = 31% MRI result Pathology pCR pRD rCR 55.5% (136/245) 44.5% (109/245) 76% had RCB1 rRD 19.5% (101/517) 26% of 101 had only DCIS 80.5% (416/517)

2090 Background: A subset of meningiomas has an aggressive clinical course requiring multimodal therapies. Yet, treatment options beyond surgery and radiation are limited. Somatostatin receptor 2 (SSTR2) is uniformly expressed in meningiomas and can be targeted by the radiopharmaceutical agent [ 177 Lu]Lu-DOTA-TATE ( 177 Lu-Dotatate). [ 68 Ga]Ga-DOTA-TATE ( 68 Ga-Dotatate) PET is emerging as a promising imaging modality to assess treatment response in SSTR2-expressing tumors. However, prospective clinical data supporting the use of 177 Lu-Dotatate and 68 Ga-Dotatate in treatment-refractory meningiomas is limited. Methods: In this multicenter, open-label, phase 2 clinical study (NCT03971461), adult patients with progressive intracranial meningiomas received 177 Lu-Dotatate at 7.4 GBq (200 mCi) every 8 weeks for 4 doses. The primary endpoint was 6-month progression-free survival (PFS-6). Up to 5 meningioma lesions per patient were assessed by gadolinium-enhanced T1 MRI every 12 weeks. 68 Ga-Dotatate PET was obtained before/after 177 Lu-Dotatate treatments. Lesional 68 Ga-Dotatate PET activity was assessed relative to liver/spleen or superior sagittal sinus (SSS). Results: 32 patients (female = 21, male = 11) with progressive meningiomas (WHO grade 1 = 7, grade 2 = 24, grade 3 = 1) were enrolled. Median age was 65.5 (range 41-78) years. All patients had at least one prior tumor surgery and at least one course of radiation. Overall, 177 Lu-Dotatate was well tolerated and the most common grade 3/4 adverse events were transient cytopenia in 15 patients (47%). One patient (3%) discontinued treatment due to grade 4 thrombocytopenia. PFS-6 was reached in 22 patients (69%), which includes 5 of 7 (71%) with grade 1 and 17 of 24 (71%) with grade 2 meningiomas. Best radiographic response by MRI was partial response (PR) in 5 (16%) and stable disease (SD) in 20 (63%) patients. Eight patients (16 lesions) were evaluable by paired MRI and 68 Ga-Dotatate PET pre- and post-treatment. Referenced to SSS, 68 Ga-Dotatate avidity reduced by ≥50% in 2 lesions (PR), 25-49% (minor response, MR) in 3 lesions and remained stable ( < 25% reduction and < 25% increase) in 11 lesions. Using liver/spleen as a reference (6 patients, 14 lesions), 68 Ga-Dotatate uptake was reduced in 9 lesions and stable in 5 lesions. 68 Ga-Dotatate PET assessments were generally concordant with MRI-based treatment response assessments. Conclusions: The primary endpoint (PFS-6) was met in this phase 2 study with 69% of patients achieving PFS-6, thereby surpassing established historical benchmarks. 177 Lu-Dotatate was generally well tolerated and deserves further study in patients with advanced meningiomas. Exploratory 68 Ga-DOTATATE PET studies showed decreased uptake in a subset of lesions and bears promise as an imaging biomarker to assess treatment response. Clinical trial information: NCT03971461 .

Importance Ischemia-reperfusion injury contributes to graft dysfunction after liver transplant. Hypothermic oxygenated perfusion (HOPE) has been shown to improve liver function, but its benefit in extended criteria donors in a US population remains unclear. Objective To assess whether back-to-base portal-venous HOPE impacts outcomes after liver transplant in the US. Design, Setting, and Participants The Bridge to HOPE Trial is a multicenter, randomized, open-label trial with 1-year follow-up. The study took place at 15 US liver transplant centers and patients were enrolled between January 2021 and May 2023. Central assessment of complications and cholangiograms for nonanastomotic biliary strictures (NAS) was blinded to treatment arm. Participants included 219 recipients of extended-criteria donor livers after brain death (DBD) and after circulatory death (DCD) who were randomized 1:1 to HOPE after static cold storage (SCS) (n = 109) or SCS only (n = 110). Randomization was performed after liver inspection and acceptance for transplant. Data were analyzed from December 2024 to July 2025. Intervention After SCS and transport, livers underwent portal-venous HOPE until implant, using the VitaSmart HOPE System. Main Outcomes and Measures The primary efficacy end point was early allograft dysfunction (EAD). Other main outcomes included model for early allograft function (MEAF) score, hospital length of stay (LOS), patient and graft survival, and biliary complications. Additional post hoc analyses were performed. Results Overall, 219 patients (82 female [37.4%] and 137 male[62.6%]) were included (DCD, 57 of 219 [26%]) with 97% (212 of 219) completing 12-month follow-up. EAD incidence was 20.2% (22 of 109) with HOPE vs 37.3% (41 of 110) with SCS (rate difference, −17.1%; 95% CI, −27.2 to −7.0; noninferiority P &amp;lt; .001; superiority P = .005). HOPE treatment led to significantly lower MEAF mean (SD) scores (HOPE group, 4.28 [1.75]; control group, 4.82 [1.85]; mean difference, −0.54; 95% CI, −1.02 to −0.06; P = .03) and shorter median LOS (hazard ratio, 1.32; 95% CI, 1.01-1.73; P = .04). NAS on imaging and 1-year survivals were comparable between groups (patients: HOPE group, 106 of 109 [97.2%] vs SCS, 106 of 110 [96.4%]; graft: HOPE group, 104 of 109 [95.4%] vs SCS, 102 of 110 [92.7%]). Post hoc analyses showed numerically less graft loss due to NAS after HOPE (4 vs 1) and less major complications (Clavien-Dindo classification ≥IIIa) per patient, respectively. Conclusions and Relevance Back-to-base portal-venous HOPE was compared with SCS alone for extended risk DBD and DCD livers. The HOPE approach was safe and associated with reduced EAD, MEAF score, and LOS. These findings support the use of HOPE as a pragmatic strategy to improve early posttransplant outcomes. Trial Registration ClinicalTrials.gov Identifier: NCT05045794 .