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554 Background: Atezo/Bev is the 1 st -line standard for advanced hepatocellular carcinoma (aHCC). Optimal 2 nd -line therapy post-Atezo/Bev remains undefined. This study evaluates continuation of atezolizumab with a MKI versus MKI alone in the 2 nd -line setting. Methods: This multicenter, randomized phase II trial enrolled patients with unresectable aHCC who progressed on Atezo/Bev. Patients were randomized 2:1 to atezolizumab plus MKI (cabozantinib or lenvatinib; Arm A) or MKI alone (Arm B). Stratification factors included MKI choice, viral etiology, and alpha-fetoprotein levels. Dual primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), duration of response (DOR), and safety. With 84 death and 89 PFS events, from 122 patients, this trial had 80% power to detect a hazard ratio (HR) of 0.556 in OS and HR of 0.571 in PFS with a one-sided type I error (alpha) of 0.05 for each endpoint. Results: Twenty patients were accrued across 5 U.S. centers, between 01/2022 and 03/2025, before early closure due to slow accrual. Eighteen received treatment (Arm A: n=13; Arm B: n=5). Baseline characteristics: median age 68 yr, extrahepatic 56%, Hep B+ 0%, Hep C+ 33%, NASH 33% and CP A (5 to 6) 100%. MKIs used were cabozantinib (Arm A: 6/13; Arm B: 4/5) and lenvatinib (Arm A: 7/13; Arm B: 1/5). Median follow-up was 28.0 months (mo), with 14 deaths reported. Median (95% CI) OS were 13.9 (7.1-Not Estimable [NE]) and 6.2 (5.1-NE) mo (Arm A and B respectively); and that of PFS 4.3 (2.3-NE) and 4.1 (3.7-NE) mo. ORR was 7.7% (1/13) in Arm A (responder received lenvatinib) and 0% (0/5) in Arm B. Grade ≥3 adverse events (at least possibly related) occurred in 46.2% of Arm A and 60.0% of Arm B patients. G3+ events occurring in >10% of patients included hypertension, fatigue, anorexia, and ALT elevation in Arm A; and hypertension, hallucination, nausea, hypomagnesemia, hypokalemia, mucositis, AST increased and colitis in Arm B. Conclusions: In this limited cohort, continuation of atezolizumab with MKI showed relative activity and manageable safety in aHCC post-Atezo/Bev. The AE profile for atezo/MKI is consistent with the known profile of respective agents. These findings support further investigation of immunotherapy-based combinations in the 2nd-line setting. Clinical trial information: NCT05168163 .

162 Background: In preclinical studies, the tryptophan-metabolizing enzyme, Indoleamine 2, 3-dioxygenase 1 (IDO1), promotes resistance to radiation in colorectal cancer, and IDO1 inhibition with epacadostat improves tumor radiosensitivity. In a phase 1 trial, patients (pts) with locally advanced rectal cancer (LARC, n=17) were treated with epacadostat in combination with short course radiotherapy (SCRT) and CAPOX which was well-tolerated, and the recommended phase 2 dose (RP2D) of epacadostat was 400mg BID. Here we report efficacy and safety from the NCI-supported phase 2 (NCT03516708) multicenter, open-label trial (treatment cohort). Methods: Pts were treated with standard of care (SOC) SCRT, then SOC neoadjuvant chemotherapy (NAC) followed by SOC surgical resection or non-operative management (NOM). Epacadostat (400 mg BID) started with SCRT and continued until starting NAC (a minimum of 21 days). Eight pts were enrolled prior to discontinuation of epacadostat by Incyte in February/March 2025. The primary endpoint is Neoadjuvant Rectal (NAR) score. In patients who underwent NOM, we calculated MRI-based tumor regression grade (MR-TRG). Secondary endpoints are pathologic complete response (pCR) rate, complete clinical response (cCR) rate, and progression free survival (PFS). Results: Table 1 summarizes baseline characteristics and endpoints (primary and secondary). NOM was pursued in 7/8 (87.5%) pts, surgical resection was performed on 1/8 (12.5%). At median follow-up of 12 months, local tumor regrowth occurred in 1 pt initially treated with NOM (after tumor regrowth, he underwent salvage surgery and is currently on surveillance). Treatment with epacadostat was interrupted in 2/8 (25%) patients due to grade 3 maculopapular skin rash. Most frequent treatment-emergent adverse events (TEAEs) regardless of causality (all grades (G)/G3-4) were bloating (75%/0%), increased ALT (62.5%/0%), increased AST (50%/0%), nausea (50%/0%), and constipation (50%/0%). Grade 3 diarrhea and grade 3 non-cardiac chest pain occurred in 1 patient each (both unrelated to epacadostat). Conclusions: Epacadostat demonstrates promising efficacy and manageable safety in patients with LARC. The biomarker cohort and correlative studies are ongoing. Clinical trial information: NCT03516708 . Baseline characteristics and endpoints. Patient Age Sex Ethnicity Stage Surgery/NOM NAR MR-TRG cCR/pCR Recurrence 1 52 M Caucasian T3N1 NOM NA 2 Y/NA No 2 45 M Caucasian T3N1 NOM NA 3 Y/NA Local tumor regrowth 3 48 M Caucasian T3N2 NOM NA 3 Y/NA No 4 61 M Caucasian T4N2 NOM NA 3 Y/NA No 5 57 M Caucasian T3N0 NOM NA 1 Y/NA No 6 60 F Caucasian T3N1 Surgery 15 3 N/ypT3N0 No 7 67 M Caucasian T4N0 NOM NA 3 Y/NA No 8 51 M Caucasian T4N2 NOM NA P NA No

We present a subset analysis on the adolescent cohort of the S1826 randomized phase three trial, comparing nivolumab, doxorubicin, vinblastine, dacarbazine (N-AVD) to brentuximab vedotin-AVD (BV-AVD) in newly diagnosed advanced-stage (AS, stages III and IV) classic Hodgkin lymphoma (cHL). Among 994 patients enrolled, 24% (n = 240) were age 12-17 years. The 3-year progression-free survival (PFS) was significantly higher in the N-AVD group (93% [95% CI, 87 to 96]) compared with the BV-AVD group (82% [95% CI, 73 to 88]; hazard ratio, 0.37 [95% CI, 0.17 to 0.80]). One N-AVD and two BV-AVD patients received protocol-specified residual site radiotherapy (RT). Rates of febrile neutropenia and sepsis were low in both groups. Severe immune-related adverse events were infrequent, although thyroid dysfunction was seen in 7% with N-AVD. Sensory neuropathy (grade ≥2) was more frequent with BV-AVD (14% v 7%) by clinician report. Although premature discontinuation of therapy was reported in 12 N-AVD patients and four BV-AVD patients, no PFS events were noted in the N-AVD group. Patient-reported outcomes indicated less toxicity with N-AVD. N-AVD demonstrated high 3-year PFS in adolescents with AS cHL, with minimal RT use. S1826 exemplifies the benefits of harmonized clinical trial protocols, resulting in timely access to novel agents for adolescents.

BACKGROUND AND OBJECTIVES: Minimum clinically important differences (MCIDs) for patient-reported outcome metrics (PROMs) in patients with cervical spondylotic myelopathy (CSM) lack consensus on the most appropriate calculation method. This retrospective study aimed to identify the optimal MCIDs for commonly used PROMs in CSM. METHODS: The CSM database from the Quality Outcomes Database SpineCORe Study Group was analyzed. Baseline, 3-month, and 24-month PROM values for Neck Disability Index (NDI), 5-dimension Euro-quality of life (EQ-5D) in quality-adjusted life years, modified Japanese Orthopaedic Association (mJOA) score, and neck/arm pain numeric rating scale (NRS) were collected. MCIDs were calculated for each PROM using previously validated techniques. MCID values were compared using the area under the curve (AUC) with the North American Spine Society satisfaction scale as an anchor. RESULTS: A total of 1141 patients with CSM undergoing surgery were included in this analysis. Improvement of ≥30% from baseline was the optimal MCID for NDI and neck/arm NRS. At 24 months, the optimal percentage cutoff MCID for these instruments resulted in AUCs of 0.76, 0.72, and 0.67, similar to the 30% improvement method, with AUCs of 0.73, 0.71, and 0.67, respectively. Numeric cutoffs (0.065 at 3 months; 0.149 at 24 months) were the superior MCIDs for EQ-5D. For mJOA score, a severity-adjusted MCID outperformed other methods, yielding an AUC of 0.67 at 24 months. MCIDs were achieved in 63% of patients for NDI, 59% for neck pain NRS, 61% for arm pain NRS, 52% for EQ-5D, and 59% for mJOA score at 24 months. CONCLUSION: Using the Quality Outcomes Database SpineCORe data set, we defined optimal MCIDs for key PROMs in CSM. A ≥30% improvement from baseline was optimal in NDI and arm/neck NRS. An absolute numeric cutoff was superior for EQ-5D (0.149 at the 24-month follow-up). A severity-adjusted MCID performed best for mJOA score. These redefined benchmarks better capture the treatment impact and guide care decisions for patients with CSM.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Small Cell Lung Cancer provide recommendations for diagnostic workup, staging, and treatment. These NCCN Guidelines Insights highlight recent updates, with a particular focus on changes to systemic therapies and radiation treatment in the NCCN Guidelines for Small Cell Lung Cancer.

The treatment landscape for multiple myeloma (MM) is evolving rapidly and includes several new options. The management must be tailored to the individual. The NCCN Guidelines for MM provide a framework to base decisions regarding diagnosis, workup, treatment, and follow-up of both newly diagnosed and previously treated relapsed/refractory MM. This manuscript outlines the recommendations from NCCN Guidelines for MM specific to newly diagnosed MM (NDMM).

Artificial intelligence (AI) is revolutionizing interventional pulmonology (IP) by enhancing diagnostics, procedural precision, and patient outcomes. AI-powered tools improve lung nodule detection, radiomics-based risk stratification, and bronchoscopic navigation. Machine learning (ML) algorithms aid in lung cancer screening by analyzing imaging data, reducing false positives, and improving early diagnosis. AI-driven robotic-assisted bronchoscopy enhances navigation and biopsy accuracy, particularly for peripheral lung lesions. Endobronchial ultrasound (EBUS) and cytopathology benefit from AI’s ability to assess lymph node malignancy and optimize rapid on-site evaluation (ROSE). AI applications extend to phenotyping chronic obstructive pulmonary disease (COPD) and identifying candidates for bronchoscopic lung volume reduction (BLVR). Deep learning (DL) models analyze computed tomography (CT) imaging and spirometry data to optimize patient selection. AI-driven algorithms are also advancing pleural effusion detection, differentiation, and classification, supporting clinical decision-making. Education and research in IP are also transforming with AI-driven simulation, virtual reality, and automated assessment tools that enhance procedural training and competency evaluation. The integration of AI into clinical work and procedural training accelerates advancements while presenting challenges in ethical AI implementation, data security, and bias mitigation. As AI continues to evolve, its role in IP will expand, improving procedural efficiency, personalizing treatment plans, and optimizing patient selection for interventions. Future developments will focus on refining AI-driven predictive analytics, enhancing robotic-assisted procedures, and integrating AI seamlessly into clinical workflows. The responsible implementation of AI in IP holds the potential to transform patient care, reduce complications, and advance precision medicine.

Objectives: To evaluate evolving management, ICU admission, and outcomes for critically ill chimeric antigen receptor (CAR) T-cell patients over a 6-year period. Design: Multicenter retrospective cohort study from January 2018 to September 2023. Setting: Eight U.S. centers. Patients: Adult CAR T-cell patients requiring ICU admission. Interventions: None. Methods: Summary statistics included mean, sd , median, and interquartile range (IQR). Fisher exact test or chi-square test were used to evaluate association between year treated and other categorical variables. Cochran-Armitage test was performed to assess significance of trends across years. Multivariable logistic regression was performed to assess covariates associated with mortality. Measurements and Main Results: Demographics, toxicity management, ICU admission, support modalities, toxicity severity, and survival (ICU, hospital, and 3-mo) were compared year-to-year. From 2018 to 2023, 2238 patients received CAR T cells, with increasing number of patients treated yearly; 398 (17.8%) required ICU care. Of those admitted to the ICU, 66.1% were male, 89.2% had lymphoma, and median age was 64 years (53–71 yr). ICU admission rates declined from 38.5% (95% CI, 31.6–45.8%) in 2018 to 16.4% in 2023 (95% CI, 13.5–19.7%; p < 0.0001). Cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome was the reason for ICU admission in 87.9%. In 2023 vs. 2018, ICU patients were older (median, 65 yr [IQR, 55–73 yr] vs. 58 yr [48–67 yr]; p = 0.003) with higher comorbidity indices (4 [4–6] vs. 3 [2–4]; p = 0.005) and more severe toxicities (≥ grade 3: 90.1% vs. 69.9%; p = 0.004). Corticosteroid use for less severe toxicities (≤ grade 2 toxicity: 73.8% vs. 40.6%; p = 0.0001) and anakinra use (56% vs. 5.5%; p < 0.0001) increased throughout the years. Mortality from cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome remained low (5.5%). Age, Sequential Organ Failure Assessment greater than or equal to 10 at ICU admission, and ICU admission for noncytokine release/neurotoxicity syndrome reasons were associated with hospital mortality (odds ratios, 1.02 [95% CI, 1–1.04; p = 0.046], 4.69 [2.44–9.01; p < 0.0001], and 3.74 [1.91–7.3; p = 0.0001], respectively). Conclusions: ICU admission rates after CAR T-cell treatment are declining. Although ICU patients are older with higher severity of illness and toxicity grades, ICU mortality after CAR T-cell therapy remains low.

Abstract Background Individuals with preclinical AD are difficult to detect using traditional clinical tools. Yet, many individuals classified as cognitively unimpaired (CU) can exhibit a heterogeneous pattern of subtle clinical abnormalities, potentially linked to early Alzheimer's disease (AD). Primary care providers often have access only to clinical tests to study at‐risk community‐dwelling older adults who visit them without cognitive complaints. Since early intervention is crucial in AD, identifying clinical tools to detect preclinical AD is important in areas with limited access to blood or imaging biomarkers. In this study, we evaluate the link between Montreal Cognitive Assessment (MoCA) total scores and AD pathology in CU individuals. Methods We studied 204 cognitively unimpaired (CU) older adults who underwent both 18 F‐FTP and 18 F‐MK6240 scans. These individuals were stratified based on their amyloid PET status, determined by visual reading, into CU A+ ( n = 35) and CU A‐ ( n = 137), as part of the ongoing HEAD study. CU adults had Clinical Dementia Rating (CDR) of 0 and were clinically identified as non‐MCI and non‐demented. Voxel‐wise linear regression models tested the association between MoCA total scores and tau pathology. Results CU A+T+ had significantly lower total MoCA scores than A‐T‐ individuals (Figure 1). Lesser MoCA total score was significantly associated with greater mediobasal temporal tau deposition, using both 18 F‐MK6240 and 18 F‐FTP [Figure 2]. When we separated the population by Aβ status, we found that these results were driven by the CU A+ group (Figure 3A) and were not present in CU A‐ individuals (Figure 3B). Discussion These findings indicate that the MoCA, a simple routine in‐office clinical test, can detect subtle cognitive dysfunction associated with preclinical AD. This suggests that simple cognitive testing can play a role in the early detection of AD and therefore an option for prescreening older adults in non‐specialized clinical settings, the initial interface for most older adults without cognitive complaints. Conclusion MoCA total, the common dementia screening test also plays a valuable role in detecting preclinical AD.

Abstract Background Individuals with spinal cord injury (SCI) are known to have high rates of cardiovascular disease that have traditionally been attributed to inability to engage in adequate intensity exercise. However, individuals with SCI also commonly experience instability in blood pressure. Blood pressure fluctuations are known to contribute to cardiovascular disease in other conditions, though this relationship in SCI is unknown. Objective To evaluate correlations between a clinical history of symptomatic blood pressure instability and objective evidence of vascular endothelial dysfunction in individuals with SCI. Design Case control. Setting Academic medical center. Participants Twenty‐four individuals with SCI, 14 uninjured controls of matched age, gender, and body mass index. Interventions Not applicable. Main Outcome Measures Symptomatic blood pressure instability was measured by the Autonomic Dysfunction Following SCI (ADFSCI) survey. Vascular endothelial dysfunction was quantified by ultrasound recordings of brachial flow mediated dilation following 5 minutes of forearm arterial occlusion. Results Total ADFSCI scores were significantly higher in individuals with SCI compared to controls (41.0 vs. 9.0, p = .002). Both percentage of brachial flow mediated dilation and consensus recommended allometrically scaled percentage of flow mediated dilation were significantly less in individuals with SCI ( p < .001 for both), demonstrating greater vascular dysfunction. More symptoms of blood pressure instability on the ADFSCI survey were correlated with more objective evidence of vascular dysfunction ( R 2 = 0.24, p = .03) for individuals with SCI. This relationship was not seen in uninjured controls. Conclusions In individuals with SCI, more severe symptoms of blood pressure instability are significantly correlated with more severe vascular endothelial dysfunction, making management of orthostatic hypotension and autonomic dysreflexia both high potential, modifiable risk factors for individuals with SCI to mitigate cardiovascular disease.