Youssef, Michael

Abstract Glioblastoma is highly vascularized with increased perfusion and prognosis remains dismal, despite improved diagnosis and aggressive multimodal treatment. The current standard of care is maximal surgical resection when feasible, followed by adjuvant radiation with concurrent chemotherapy, temozolomide. However, treatment resistance and tumor recurrence pose a considerable challenge for stratifying patients for optimal treatment planning. Current radiological assessment of glioblastoma therapy response predominantly relies on morphological measures; that may not accurately capture early microscopic changes or therapeutic efficacy. We have developed and validated an advanced imaging method, Arterial Spin Labeling (ASL) MRI that enable noninvasive spatial assessment of the entire tumor. ASL-MRI uses water within the blood as an endogenous tracer and measures perfusion without the need for exogenous gadolinium-based contrast agent. The objective of this study was to investigate ASL measured quantitative perfusion after surgery to predict survival in glioblastoma patients undergoing the standard of care chemoradiation treatment. In this prospective, IRB-approved study, twenty-three adults with glioblastoma participated for longitudinal MRI. Progression-free survival (PFS) and overall survival (OS) were recorded for each patient. A baseline MRI scan was performed prior to chemoradiation treatment and after surgery utilizing a 3D ASL sequence. All structural images were co-registered to T1 post-contrast images. Tumor regions of interest (ROIs) such as enhancing tumor (ET), tumor core, whole tumor, and necrosis were manually segmented. Cerebral blood flow maps were calculated and mean perfusion values (MPV) within ET ROIs were extracted. Scatter plot of MPV and Kaplan-Meier graphs were generated using GraphPad Prism. Based on median survival of 420 days, patients were categorized into short (≤420 days) or long (>420 days) survival. A threshold ASL measured perfusion value of 30 mL/100g/min distinguished survival groups; hyper-perfusion correlated with shorter OS, while hypo-perfusion linked to longer OS. The mean±SD of PFS and OS for patients with shorter survival were 119±42 days and 230±117 days respectively, while for longer survival were 624±285 and 726±210 days respectively, and the values were statistically different (P<0.001for both). Kaplan-Meier curves showed significant OS and PFS differences (p<0.015, Hazard Ratio=3.056). Our data indicate that ASL measured baseline perfusion, after surgery and before chemoradiation treatment can benefit in predicting survival and treatment stratification in glioblastoma patients. ASL measured perfusion can be performed during radiation treatment and could provide valuable information that can be incorporated into emerging treatment strategies such as adaptive radiation. Citation Format: Durga Udayakumar, Limin Zhou, Marco Pinho, Yiming Wang, Ben Wagner, Michael Youssef, Joseph Maldjian, Ananth Madhuranthakam. Noninvasive magnetic resonance imaging measured quantitative perfusion as predictive and prognostic biomarker in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7163.

Abstract GBM AGILE(NCT03970447) is a phase 2/3 Bayesian adaptive registration platform trial testing multiple therapies against a common control. Paxalisib, a PI3K/mTOR inhibitor, is the 3rd arm in the trial to conclude evaluation. METHODS Paxalisib was open to patients with newly diagnosed unmethylated (NDU) and recurrent (RD) glioblastoma, with three possible signatures: NDU, RD, and All(NDU+RD). Arm enrollment occurred Dec2020 through May2022. Control patients were enrolled from study initiation (July2019) and were treated with temozolomide(NDU) or lomustine(RD). GBM AGILE investigational arms have 1 or 2 stages, with adaptive randomization in stage 1 and fixed randomization if arms continue to stage 2. Efficacy is based on OS hazard ratio(HR) of Arm/Control. Efficacy goal is final Bayesian probability ≥ 98% for HR<1.00 in combined Stages. An Arm continues to Stage 2 if Bayesian predictive power (PP) ≥ 0.8. An Arm stops accruing in Stage 1 if it reaches maximal sample size(N) or does not meet a minimum efficacy threshold (PP<0.25 for all signatures when N>50). Clinical cut-off is 12 months after accrual stops. The maximum N for paxalisib was approximately 150(Stage 1) and 50(Stage 2). RESULTS After paxalisib reached >150 patients in Stage 1, accrual stopped [Paxalisib/control N 54/75(NDU), 100/188(RD)]. Neither PP thresholds for moving to Stage 2 nor stopping for minimum efficacy were met. Following an unplanned public disclosure that the arm did not continue to stage 2, clinical cut-off for final analysis (planned May2023) was updated to public disclosure date (August2022). At final analysis mean HRs were 0.89(NDU), 1.25(RD), 1.05(All), probabilities of HR<1.00 of 0.72(NDU), 0.076(RD), 0.398(All). Model estimated median OS paxalisib/control (months) were 14.77/13.84(NDU) and 8.58/10.06(RD). CONCLUSION Paxalisib did not show survival benefit over cumulative control in final primary analysis; additional secondary analyses are being considered. GBM AGILE continues to rapidly and efficiently assess therapies in ND and RD glioblastoma.

Abstract Background Homelessness is an important public health issue with a prevalence around 4.2% in the United States. Homelessness has been associated with lack of access to healthcare services, poor quality of care, and negative health outcomes. However, there is limited data on clinical outcomes among homeless individuals with Crohn’s disease (CD). Aims In this study, we examine inpatient outcomes including endoscopy utilization, surgical treatment, and post-operative complications among homeless patients with CD. Methods The Healthcare Utilization Project (HCUP) State Inpatient Databases from New York, Arizona, Massachusetts and Florida for 2013 and 2014 were used to identify adults ≥18 years admitted with CD identified by International Classification of Diseases, Ninth Revision codes. Homeless patients were then identified, and propensity score matched using a one-to-ten greedy nearest-neighbor approach to non-homeless patients to balance the distribution of baseline covariates. Differences in outcomes including endoscopy utilization, surgical treatment and post-operative complications were reported as odds ratios (ORs) and 95% confidence intervals (CI). Results A total of 70,457 CD hospitalizations were identified, of which 469 (0.6%) were associated with homelessness. We matched 440 homeless patients with 4,400 housed patients with CD. Homeless individuals had a higher proportion of males (p=0.002), tended to be older (p=0.035), and had more comorbidities than non-homeless individuals. There was no difference in mortality between non-homeless and homeless patients (OR 1.6, 95% CI 0.72-3.57). Endoscopy utilization was comparable between non-homeless and homeless patients with CD including gastroscopy (OR 0.71, 95% CI 0.40-1.18), colonoscopy (OR 0.80, 95% CI 0.31-1.69), and sigmoidoscopy (OR 0.37, 95% CI 0.02-1.74) [Figure 1]. Surgical treatment was also comparable, except for lower rates of bowel resection among homeless patients (OR 0.55, 95% CI: 0.29-0.93). The two groups also had similar rates of post-operative complications including pulmonary, cardiovascular, gastrointestinal, and infectious complications (Figure 1). Conclusions Homeless patients with CD have comparable endoscopy utilization and surgical treatment as non-homeless patients, except for lower bowel resection rates. Postoperative complications are also similar between the two groups. Future studies are needed to better understand the impact of homelessness on health outcomes and healthcare service utilization among patients with CD. Figure 1. Endoscopy utilization, surgical treatment, and post-operative complications among homeless and non-homeless individuals using 1:10 propensity matching Funding Agencies None

BACKGROUND: The impact of English proficiency on gastrointestinal bleeding (GIB) outcomes remains unclear. In this analysis, we compare inpatient GIB outcomes between patients with English as their primary language (EPL) and those with a primary language other than English (PLOE). METHODS: Using the 2019 State Inpatient Databases for New Jersey, Maryland, and Michigan, we created an analysis cohort of GIB hospitalizations using International Classification of Diseases, 10th Revision codes. Patients were stratified by primary language (EPL vs PLOE) and type of bleeding (variceal upper GI bleeding [VUGIB], nonvariceal upper GI bleeding [NVUGIB], and lower GI bleeding (LGIB)]. Regression analyses were used to compare mortality, 30-day readmissions, and length of stay. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were reported. P < 0.05 was considered statistically significant. RESULTS: In the cohort, 5.5%–10% of the patients spoke a primary language other than English. Endoscopy utilization was lower among patients with PLOE vs EPL for NVUGIB (17.2% vs 21.2%, P < 0.001) and LGIB (26.3% vs 29.2%, P = 0.027). Patients with PLOE had higher odds of dying of VUGIB (aOR 1.45, 95% CI 1.16–2.48) and LGIB (aOR 1.71, 95% CI 1.22–2.12). Patients with PLOE were also more likely to be readmitted after NVUGIB (aOR 1.75, 95% CI 1.64–1.81). However, after controlling for the percentage of patients with PLOE discharged from each hospital, the disparities in mortality and readmissions were no longer detected. DISCUSSION: Disparities exist in GIB outcomes among patients with PLOE, but these gaps narrow at hospitals with higher percentages of patients with PLOE. Cultural and linguistic competence may improve outcomes in this vulnerable group.

AbstractBackground and AimThe impact of the Coronavirus disease‐2019 (COVID‐19) pandemic on patients with liver disease is not well described at the population level in the United States. We used the largest, nationwide inpatient dataset to describe inpatient liver disease outcomes in the United States during the first year of the pandemic (2020) using 2018 and 2019 as comparator years.MethodsUsing the National Inpatient Sample (2018–2020), we explored year‐to‐year and 2020 month‐to‐month trends in hospitalizations, length of stay, and inpatient mortality for liver‐related complications including cirrhosis, alcohol‐associated liver disease (ALD) and alcoholic hepatitis using regression modeling. We reported relative change (RC) in the study period.ResultsDecompensated cirrhosis hospitalizations decreased in 2020 compared with 2019 (RC: −2.7%, P < 0.001) while all‐cause mortality increased by 15.5% (P < 0.001). Hospitalizations for ALD increased compared with pre‐pandemic years (RC: 9.2%, P < 0.001) with a corresponding increase in mortality in 2020 (RC 25.2%, P = 0.002). We observed an increase in liver transplant surgery mortality during the peak months of the pandemic. Importantly, mortality from COVID‐19 was higher among patients with decompensated cirrhosis (adjusted odds ratio [OR] 1.72, 95% confidence interval [CI] [1.53–1.94]), Native Americans (OR 1.76, 95% CI [1.53–2.02]), and patients from lower socioeconomic groups.ConclusionsCirrhosis hospitalizations decreased in 2020 compared with pre‐pandemic years but were associated with higher all‐cause mortality rates particularly in the peak months of the COVID‐19 pandemic. In‐hospital COVID‐19 mortality was higher among Native Americans, patients with decompensated cirrhosis, chronic illnesses, and those from lower socioeconomic groups.