Prognostic Impact Research Articles

Integrative pan-cancer analysis reveals a common architecture of dysregulated transcriptional networks characterized by loss of enhancer methylation

Aberrant DNA methylation contributes to gene expression deregulation in cancer. However, these alterations’ precise regulatory role and clinical implications are still not fully understood. In this study, we performed expression-methylation Quantitative Trait Loci (emQTL) analysis to identify deregulated cancer-driving transcriptional networks linked to CpG demethylation pan-cancer. By analyzing 33 cancer types from The Cancer Genome Atlas, we identified and confirmed significant correlations between CpG methylation and gene expression (emQTL) in cis and trans, both across and within cancer types. Bipartite network analysis of the emQTL revealed groups of CpGs and genes related to important biological processes involved in carcinogenesis including proliferation, metabolism and hormone-signaling. These bipartite communities were characterized by loss of enhancer methylation in specific transcription factor binding regions (TFBRs) and the CpGs were topologically linked to upregulated genes through chromatin loops. Penalized Cox regression analysis showed a significant prognostic impact of the pan-cancer emQTL in many cancer types. Taken together, our integrative pan-cancer analysis reveals a common architecture where hallmark cancer-driving functions are affected by the loss of enhancer methylation and may be epigenetically regulated.

Analysis of immune status and prognostic model incorporating lactic acid metabolism-associated genes.

Cancer development is intricately linked with metabolic dysregulation, including lactic acid metabolism, which plays a pivotal role in tumor progression and immune evasion. However, its specific implications in gastric adenocarcinoma (STAD) remain unclear. This study introduces a novel methodology to evaluate lactic acid metabolism comprehensively in STAD, aiming to elucidate its prognostic significance and impact on immunotherapy efficacy. Targeted therapies directed at key lactic acid metabolism genes (LMGs) identified within the tumor microenvironment (TME) hold promise for personalized treatment strategies. Lactic acid metabolism patterns were assessed in 415 STAD patients using a panel of 21 LMGs. Cox regression and Lasso regression analyses were employed to develop a predictive risk model based on differentially expressed genes (DEGs). Validation of the model was conducted using independent cohorts from the GEO and TCGA databases, as well as additional datasets focused on immunotherapy responses. Further investigations into TME dynamics of lactic acid metabolism included functional assays targeting SLC16A3, a pivotal gene identified through our analyses. Patients were stratified into distinct risk groups based on their lactic acid metabolism profiles. Low-risk patients exhibited attenuated lactic acid metabolism, correlating with favorable clinical outcomes characterized by prolonged survival and enhanced responsiveness to immunotherapy. Notably, tumor cells within the TME demonstrated heightened levels of active lactic acid metabolism, particularly impacting tumor-infiltrating lymphocytes such as CD8 + T cells and regulatory T cells. Mechanistically, SLC16A3 emerged as a critical regulator promoting STAD cell proliferation, invasion, and migration while modulating the metabolic landscape. This study underscores the prognostic value of a lactic acid metabolism-based model in STAD, providing insights into its potential as a predictive biomarker for patient stratification and therapeutic targeting. The findings highlight SLC16A3 as a promising candidate for therapeutic intervention aimed at modulating lactic acid metabolism in the TME, thereby advancing personalized treatment strategies in gastric cancer management.

Risk factors and prognostic impact of new decompensated events in hospitalized patients with decompensated cirrhosis.

Decompensated cirrhosis (DC) is prone to recurrent episodes of decompensation following the initial event. This study aimed to identify the risk factors for subsequent decompensation and assess their impact on the outcomes of patients hospitalized for DC. Patients with DC were divided into two groups based on the occurrence of new decompensated events during hospitalization. Logistic regression analysis was employed to identify risk factors for new decompensation. The Cox proportional hazards model was used to evaluate the relationship between new decompensation and short-term mortality risk in these patients. The study cohort consisted of 339 patients with DC, with a median age of 57 years. During hospitalization, 83 patients (24.5%) experienced new decompensated events, with bacterial infections (BIs) being the most common (n = 46, 13.6%). Multivariate analysis revealed that the Model for End-Stage Liver Disease (MELD) score at admission (OR = 1.06, 95% CI: 1.02-1.11, P = 0.005) was the sole risk factor for new decompensation during hospitalization. Patients who experienced new decompensation had significantly higher 28-day (28.9% vs. 7.0%, P < 0.001) and 90-day (33.7% vs. 15.2%, P < 0.001) transplant-free mortality compared to those who did not. After adjusting for white cell count, C-reactive protein, and MELD score, new decompensation during hospitalization was identified as an independent risk factor for 28-day and 90-day mortality (HR = 2.63, 95% CI: 1.42-4.87, P = 0.002 and HR = 1.73, 95% CI: 1.04-2.88, P = 0.033, respectively). Patients with high MELD scores are susceptible to new decompensation during hospitalization, and the occurrence of new decompensation adversely affects short-term mortality in patients with DC.

Prognostic impact of adipose tissue loss at 1month after surgery in patients with gastric cancer.

The postoperative impact of short-term changes in skeletal muscle loss (SML) and adipose tissue loss (ATL) on treatment outcomes is unclear in patients with gastric cancer (GC). We investigate the role of SML and ATL at 1month after surgery in determining postoperative survival and recurrence rates in patients with GC. We analyzed 540 patients with GC and assessed their skeletal muscle mass, visceral fat mass, and subcutaneous fat mass using computed tomography scans preoperatively and 1month postoperatively. Patients were categorized into high and low groups based on their levels of SML, visceral ATL (v-ATL), and subcutaneous ATL (s-ATL). Additionally, they were classified into three groups (high ATL, intermediate ATL, and low ATL) based on their v-ATL and s-ATL measurements. Patients with higher v-ATL and s-ATL had lower overall survival (OS) and recurrence-free survival (RFS) rates. High ATL was an independent prognostic factor for decreased OS (hazard ratio [HR] 2.27; 95% confidence interval [CI] 1.16-4.42; and P=0.02) and RFS (HR 2.51; 95% CI 1.34-4.71; and P=0.004) rates. A reduction in adipose tissue volume shortly after surgery (1month) could potentially indicate an increased risk of recurrence and mortality in patients with GC.

Association Between Wound Healing and the Japanese Below-the-Knee Chronic Total Occlusion Score in Patients With Chronic Limb-Threatening Ischemia After Endovascular Therapy.

In the current study, we hypothesized that the Japanese below-the-knee chronic total occlusion score could be used to stratify the lesion difficulty of endovascular therapy for below-the-knee chronic total occlusion through angiographic evaluation. We thus aimed to evaluate the prognostic impact of the Japanese below-the-knee chronic total occlusion score in patients with chronic limb-threatening ischemia after successful endovascular therapy for below-the-knee chronic total occlusion. This was a retrospective, single-center observational study. We enrolled 139 consecutive patients with chronic limb-threatening ischemia (149 limbs), who underwent successful endovascular therapy for chronic total occlusion between February 2008 and December 2017. The Japanese below-the-knee chronic total occlusion score was assessed based on the definition of the target arterial path. The evaluation items were the rate of amputation-free survival and wound healing at 1 year, and the association between wound healing at 1 year and the Japanese below-the-knee chronic total occlusion score. The rates of amputation-free survival and wound healing at 1 year were 88.0 and 56.4%, respectively. Multivariate Cox proportional hazard analysis identified direct flow to the wound (hazard ratio: 2.34, 95% confidence interval: 1.28-4.66; p<0.01); Wound, Ischemia, and foot Infection stages 1-3 (hazard ratio: 2.81, 95% confidence interval: 1.63-5.18; p<0.01); and a Japanese below-the-knee chronic total occlusion score ≤1 (hazard ratio: 1.70, 95% confidence interval: 1.02-2.98; p=0.04) to be predictors of wound healing. A Japanese below-the-knee chronic total occlusion score ≤1, direct flow to the wound, and Wound, Ischemia, and foot Infection stages 1-3 were found to be associated with wound healing after successful endovascular therapy for below-the-knee chronic total occlusion in patients with chronic limb-threatening ischemia. This study was conducted to evaluate the prognostic impact of the Japanese below-the-knee chronic total occlusion (J-BTK CTO) score in patients with chronic limb-threatening ischemia (CLTI) after successful endovascular treatment (EVT). The results showed that the J-BTK CTO score not only evaluates the difficulty of EVT but also can predict limb prognosis. Using the J-BTK CTO score, it seems possible to predict the limb prognosis and make it useful in clinical practice.

Prognostic impact of the newly revised IASLC proposed grading system for invasive lung adenocarcinoma: a systematic review and meta-analysis.

This study aimed to evaluate the prognostic value of the newly revised International Association for the Study of Lung Cancer (IASLC) grading system (2020) on the 5-year overall survival (OS) and recurrence-free survival (RFS) in patients with lung adenocarcinoma (LADC). Clinical studies that investigated the prognostic value of revised IASLC staging system in patients with LADC were retrieved from the PubMed, Web of Science, ScienceDirect, and Cochrane Library databases. This study was conducted in accordance to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and checklists. Based on inclusion and exclusion criteria, we included 12 studies for analysis. The grade of LADC was assessed by revised IASLC system, which included three grades. Compared to Grade 3 LADC, grade 1 (total [95% CI]: 1.38 [1.19, 1.60]) and grade 2 (total [95% CI]: 1.29 [1.15, 1.44]) LADC had higher 5-year OS rates. Similarly, Grade 1 (total [95% CI]: 1.76 [1.42, 2.18]) and Grade 2 (total [95% CI]: 1.51 [1.28, 1.77]) had higher 5-year RFS rates Grade 3 LADC. However, 5-year OS and RFS had no significant difference between Grade 1 and Grade 2 patients. This systematic review and meta-analysis provides evidence that the newly revised IASLC grading system is significantly associated with the prognosis of patients with LADC, where Grade 3 indicated unfavorable prognosis.

Prognostic significance and risk factors of mediastinal lymph node metastasis in esophagogastric junction cancer: a single-center, retrospective study.

Although the optimal extent of lymph node dissection in esophagogastric junction cancer (EGJC) has been reported, the efficacy of mediastinal lymph node dissection remains unclear. We aimed to identify risk factors for mediastinal lymph node metastasis and its prognostic impact in patients with EGJC. A total of 100 consecutive patients who underwent curative surgery for EGJC were eligible. We examined the rates of metastasis, prognosis, and therapeutic value index at each mediastinal lymph node station. In addition, multivariate analyses were performed to identify risk factors for mediastinal lymph node metastasis. The rates of upper, middle, and lower mediastinal lymph node metastases were 12.0%, 20.7%, and 13.2%, respectively. The 5-year overall survival rate was lower in patients with mediastinal lymph node metastasis than in those without mediastinal lymph node metastasis (11.1% vs. 59.2%, p < 0.01). The therapeutic value index was 0 in patients with upper/middle mediastinal lymph node metastasis, and mediastinal lymph node metastasis was an independent prognostic factor (hazard ratio 6.59, 95% confidence interval [CI] 2.48-17.9, p < 0.01). Additionally, the length of esophageal invasion and the presence of hiatal hernia were independent predictors of mediastinal lymph node metastasis (odds ratio 8.21, 95%CI 1.44-46.8, p = 0.02 and odds ratio 7.13, 95%CI 1.22-41.8, p = 0.03). No survival benefit of mediastinal lymph node dissection was observed. Intensive multidisciplinary treatment could be considered in patients with predicted mediastinal lymph node metastasis, such as those with longer esophageal invasion and those with hiatal hernia.

Comprehensive analysis of radiologic cancer-free (rCF) status through various treatment approaches in advanced-stage hepatocellular carcinoma

Introduction In the realm of oncology, the pinnacle of therapeutic success is achieving a state where the patient is entirely free of cancer, i.e. ‘cancer-free’. This benchmark should not only apply to early-stage malignancies but should also be the standard aim for advanced-stage diseases, including hepatocellular carcinoma (HCC). However, there is a glaring gap in the research landscape concerning the understanding of what cancer-free status truly means for advanced-stage HCC. Our study sheds light on the profound implications of reaching a cancer-free by radiological assessments in patients with advanced-stage HCC. Methods We established a database tracking the full clinical course of all patients with HCC (from 2003–2022). We identified the initial instances of macrovascular invasion or extrahepatic spread. We defined radiologic cancer-free (rCF) as cases in which no recurrence was observed for at least 2 months following curative treatment or complete response to systemic therapies. The frequency of achieving rCF status was investigated, categorised by patients’ background. Results We identified 795 patients with advanced-stage HCC. The rCF rate was 8.7%. Patients who achieved rCF status had significantly better prognoses compared to those who did not (p &lt; 0.001). In the decision tree analysis, the number of tumors ≥8 was the strongest factor making it difficult to achieve rCF status. Analysis of stage progression patterns revealed varying background characteristics at the time of advanced-stage diagnosis, with discrepancies in rCF rates. Conclusions Despite the low rate of achieving rCF status, the prognostic impact was significant. Patients with certain tumor characteristics had a higher likelihood of achieving rCF status. The distribution of tumor conditions varies based on the pattern of progression, which affects the likelihood of achieving a rCF status.

GATA6 amplification is associated with improved survival in TP53-mutated unresectable pancreatic cancer

Abstract Objectives: GATA6 expression has been recently recognized as a favorable prognostic marker of pancreatic cancer whereas TP53 is recognized as a poor prognostic marker. We evaluated treatment outcomes by genetic alterations in TP53 and GATA6 to determine the prognostic and predictive impact of co-alterations. Methods A single institution retrospective analysis was performed on patients diagnosed with PDAC between 2014 to 2023. TP53 genotype and GATA6 amplification status were included in an analysis of overall survival (OS) and progression free survival (PFS). Previously published patient-derived organoids were used to investigate correlation between genetic status and drug sensitivity. Results Patients with TP53 mutations had worse OS compared to the wild type TP53 population. In general, patients with GATA6 amplification had better OS and a trend towards better PFS than the non-amplified population. Among patients with a TP53 mutation, patients with GATA6 co-alteration had longer OS compared to those who were not GATA6 amplified. In contrast, among patients who were TP53 wild type, the presence or absence of a GATA6 amplification did not impact OS or PFS. GATA6 genotype was not associated chemotherapy drug response in an organoid pharmacotyping model. Conclusions We found that GATA6 amplification appeared to attenuate poor prognosis observed in TP53-mutant patients regardless of the type of standard chemotherapy received, suggesting the GATA6 amplification is a prognostic biomarker but not a predictive biomarker of standard-of-care chemotherapy.

Prognostic impact of the metabolic syndrome and its components in acute type a aortic dissection after surgery: a retrospective study.

This study aimed to explore whether metabolic syndrome (MetS) and its components are associated with poor outcomes in patients with acute type A aortic dissection (ATAAD) after surgery. This study included 353 patients who had undergone surgery. Demographic and clinical characteristics of the patients were collected. Subgroup, mixed-model regression, score systems, and receiver operating characteristic curve (ROC) analyses were performed. Overall, 353 inpatients were assigned to the poor outcome group (n = 69) and control group (n = 284) with or without MetS. Compared to the control group, the incidence of MetS was higher in the poor outcome group. Poor outcomes were present in 0%, 4.4%, 12.3%, 47.6%, 71.4%, and 100% of the six groups who met the diagnostic criteria for MetS 0, 1, 2, 3, 4, and 5 times, respectively. For multivariable logistic regression, Body mass index (BMI) quartiles remained risk factors for poor outcomes after adjustment for other risk factors. After adjusting for potential confounding factors, the MetS was found to be an independent risk factor in several models. Assigning a score of one for each component, the AUC was 0.877 (95%CI: 0.823-0.923) in all patients, 0.864 (95%CI: 0.7945-0.935) in MetS, and 0.700 (95%CI: 0.567-0.833) in non-MetS by receiver operating characteristic. MetS, especially BMI, confer a greater risk of poor outcomes in ATAAD after surgery during the 3-year follow-up.

Inflammatory markers correlate with lymphocytes infiltrating and predict immunotherapy prognosis for esophageal cancer.

Aim: To investigate the prognostic value of inflammatory markers in esophageal squamous cell carcinoma (ESCC) patients treated with immune checkpoint inhibitors (ICIs).Materials & methods: The infiltration of CD3+ and CD8+ T cells in tissue microarraysfrom 180 patients who underwent radical esophagectomy was detected using immunohistochemistry. A separate cohort of 351 patients with metastatic/recurrent or unresectable ESCC treated with ICIs was enrolled for further investigation. The overall survivaldifference among groups was assessed using Kaplan-Meier analysis. Cox proportional hazards models were employed to investigate the prognostic impact of the inflammatory markers, along with other factors.Results: Decreased inflammation was found to be associated with increased CD3+ and CD8+ T-cell infiltration and a better prognosis. Then, the value of inflammatory markers in predicting survival in 351 ESCC patients receiving immunotherapy was validated. Ultimately, the systemic immune-inflammation index was identified as an independent prognostic factor for overall survival. Additionally, the patients with no distant organ metastasis, or treated by first-line immunotherapy combined with concurrent chemoradiotherapy can considerably prolong survival.Conclusion: Inflammation is associated with the level of tumor infiltrating lymphocytes and that the systemic immune-inflammation index is an effective prognostic predictor for ESCC patients treated with ICIs.

Abstract 4132909: Hemodynamic Indices of Right Ventricular Function Differentially Predict Adverse Clinical Outcomes in Heart Failure with Preserved vs Reduced Ejection Fraction

Background: While the critical role of right ventricular dysfunction (RVD) in heart failure (HF) is increasingly recognized, the prevalence and prognostic impact of RVD across HF subtypes is poorly understood. Research Questions/Aims: We aimed to characterize differences in hemodynamic indices of RV function among patients with HF with preserved vs reduced ejection fraction (HFpEF, EF≥50% vs HFrEF, EF&lt;50%) and to examine associations of RVD with longitudinal clinical outcomes by HF subtype. Methods: We identified patients with prevalent HF undergoing clinically indicated right heart catheterization at Massachusetts General Hospital (2005-2016). We examined three RV hemodynamic indices: right atrial to wedge pressure ratio (RA/PCWP), RV stroke work index (RVSWI), and pulmonary artery pulsatility index (PAPi). We used multivariable linear regression to assess differences in RV indices in HFpEF vs HFrEF. We then used Cox models to examine the association of each index with HF hospitalizations (HFH), major adverse cardiac events (MACE), and death, stratified by HF subtype. Models were adjusted for age, sex, BMI, hypertension, diabetes, lung disease, sleep apnea, and prior MI. Results: Of 2,062 patients (age 66 years, 33% women), 1,242 (60%) had HFrEF and 820 (40%) had HFpEF. RVD (RVSWI &lt;450 mm Hg*ml/m 2 ) was present in 27% of HFrEF vs 21% of HFpEF patients. Those with HFpEF had higher RA/PCWP (β 0.12, SE 0.05, p=0.012) and RVSWI (β 0.22, SE 0.05, p&lt;0.001) relative to HFrEF. Over 4.1 median years follow-up, 915 HFH, 1,066 MACE, and 1,116 death events occurred. Among those with HFrEF, lower PAPi was associated with greater risk of HFH (HR 0.84 (0.77, 0.92); p&lt;0.001) and MACE (HR 0.88 (0.81, 0.96); p=0.003), and higher RVSWI was associated with greater risk of death (HR 1.17, (1.07, 1.27); p&lt;0.001, Figure ). In contrast, in those with HFpEF, only higher RA/PCWP was associated with greater risk of death (HR 1.11 (1.00, 1.23); p=0.042). Conclusion: RVD occurs frequently in both HFrEF and HFpEF, and hemodynamic measures of RV function are associated with greater risk of MACE, death, and HFH. Importantly, the prognostic value of RV indices varied by HF subtype, highlighting key differences in the role of RVD in HFrEF vs HFpEF.

Abstract 4130072: Prognostic Impact of Renal Microcirculatory Dysfunction in Heart Failure Assessed by the Advanced Doppler technique, Superb Microvascular Imaging

Aims: The significance of cardio-renal interactions in heart failure (HF) prognosis has become increasingly evident, yet there are no established methods to assess them. To address this issue, we propose a novel approach using Superb Microvascular Imaging (SMI), an ultrasound method that that enables detailed visualization of microvascular flow, to assess renal microcirculation. Methods: We retrospectively analyzed 78 patients who underwent renal ultrasonography using SMI from October 2020 to May 2023. We measured changes over time of Vascular Index (VI), which quantifies the blood flow signal area in the region of interest on the SMI image (Figure 1). Key measurements included Maximum VI (Max.VI), Minimum VI (Min.VI), and the cyclic variation of VI, calculated as the intrarenal perfusion index (IRPI) = (Max.VI - Min.VI) / Max.VI within one cardiac cycle. The primary endpoint of this study was a composite event (CE), defined as a composite of all-cause death and unplanned hospitalization for worsening HF. Results: During a mean follow-up period of 1.6±0.8 years, 13 of 78 patients (17%) experienced a CE. Compared with patients without CE, those with CE had significantly lower Max.VI (0.28±0.15 vs 0.46±0.18, p=0.002) and Min.VI (0.10±0.12 vs 0.22±0.14, p=0.007), and IRPI was significantly higher in the event group (0.68±0.19 vs 0.55±0.17, p=0.018). In univariable Cox regression analyses, Max.VI (HR 0.35, 95%CI 0.17-0.71, p=0.004), Min.VI (HR 0.28, 95%CI 0.10-0.75, p=0.012), IRPI (HR 1.97, 95%CI 1.11-3.51, p=0.021), creatinine (Cr) (HR 1.67, 95%CI 1.26-2.21, p&lt;0.001) and estimated right atrial pressure by echocardiography (eRAP) (HR 4.22, 95%CI 1.42-12.5, p&lt;0.001) were significantly associated with CE. In multivariable Cox regression analyses, Min.VI remained significantly associated with CE in the model adjusted for Cr (HR 0.35, 95%CI: 0.13-0.92, p=0.033), and in the model adjusted for eRAP (HR 0.11, 95%CI: 0.11-0.82, p=0.019). ROC curve analysis showed that, although not statistically significant, the predictive power of Min.VI was superior to that of Cr and eRAP (Figure 2). Stratifying patients by a Min.VI cut-off value of 0.08, determined through ROC analysis, showed that those with Min.VI &lt; 0.08 had a significantly poorer prognosis (log-rank p&lt;0.001) (Figure 3). Conclusion: The use of Superb Microvascular Imaging to assess renal circulation provides new insights into the prognosis of HF and allows risk stratification beyond conventional markers.

Abstract 4141475: Prognostic Impact of Acute Kidney Injury Following Repair of Stanford Type A Aortic Dissection: A Systematic Review and Meta-Analysis

Background: Acute Kidney Injury (AKI) is a multifactorial complication following repair of Stanford Type A aortic dissection (TAAD) with an alarmingly high incidence, varying from 20 to 77%. Postoperative AKI following life-threatening disease tends to be much more complex. However, the exact role of postprocedural AKI in the prognosis of patients undergoing TAAD repair has not been elucidated. Aims: This meta-analysis aimed to evaluate the prognostic significance of postprocedural AKI in patients undergoing TAAD repair. Methods: A literature search was conducted using PubMed, EMBASE, and SCOPUS databases. The primary endpoint was 30-day mortality with several secondary endpoints. Risk ratios (RR) with 95% confidence intervals (CIs) were pooled using Review Manager software. Statistical significance was set at p &lt;0.05. Random-effects meta-analyses were performed for all outcomes. Results: Our analysis included 21 studies comprising 10396 patients. Patients with AKI exhibited a significantly higher risk of 30-day mortality (RR=3.98; 95% CI: 3.04-5.22; p&lt;0.00001; I 2 =57%), stroke (RR= 2.05; 95% CI: 1.68-2.50; p&lt;0.00001; I 2 =32%), dialysis requirement (RR= 32.9; 95% CI: 10.39-104.24; p&lt;0.00001; I 2 =90%) (Figure 1), cardiovascular complications (RR= 2.85; 95% CI: 1.65-4.92; p&lt;0.0002; I 2 =85%), sepsis (RR= 4.92; 95% CI: 2.62-9.24; p&lt;0.00001; I 2 =64%), and re-exploration for bleeding (RR=2.46; 95%CI: 1.79-3.39; p&lt;0.00001; I 2 =58%) compared to those without AKI (Figure 2). Conclusion: Patients with AKI demonstrated a significantly increased risk of mortality, stroke, need for dialysis, sepsis, postoperative cardiovascular complications, and re-exploration for bleeding. Further prospective studies are required to better understand the prevention strategies and long-term effects on prognosis of AKI post-repair for TAAD.

Abstract 4127891: Value of Left Ventricular and Left Atrial Strains in Loeffler Endocarditis and Hypereosinophilic Syndrome

Background: Hypereosinophilic syndrome (HES) is a rare disease that causes organ damage and thrombosis due to sustained eosinophilia of the blood or tissues. Loeffler endocarditis (LE) is defined as cardiac involvement in the setting of HES. There are limited data on the diagnostic and prognostic impact of strain imaging on LE. Methods: A single-center retrospective cohort study was performed. Patients with eosinophilia between January 2000 and January 2023 were identified. We included patients who met the current diagnostic criteria for HES and underwent echocardiography prior to treatment. LE was defined as the presence of eosinophils in the myocardium by an endomyocardial biopsy, endocardial thickening, or left ventricular thrombus due to HES. We evaluated the composite events defined as CV death and stroke at diagnosis and during follow-up. Results: Of 1,664 patients with eosinophilia, 34 patients with HES were included (10 with LE and 24 without LE). In the entire cohort, the mean age was 57 ± 16 years and 41% were male. The median follow-up duration was 85 months (25th -75th percentile: 41-145 months). The composite events occurred in 6 patients. Left ventricular ejection fraction (LVEF) was similar in both groups (60% vs. 61%, p = 0.691). Patients with LE had significantly lower left ventricular global longitudinal strain (LV-GLS) (-9.7% vs. -15.5%, p = 0.001), left atrial (LA) reservoir strain (21.0% vs. 32.1%, p = 0.021) and LA conduit strain (-9.7% vs. -19.2%, p &lt;0.001), compared to patients without LE. There were no significant differences in LA booster strain (-11.3% vs. -12.8%, p = 0.606) and right ventricular free wall strain (-17.5% vs. -23.4%, p = 0.083). All LE patients and half of non-LE patients had LV-GLS worse than -16 %. There was a significant difference in the compsoite events for patients with LV-GLS worse than -16% (28.6% vs. 0.0%, p = 0.049). Conclusions: LE was associated with significantly worse LV-GLS and left atrial strain compared to patients without LE. Worse LV-GLS was associated with a higher frequency of the composite events.

Abstract 4136085: The Prognostic Impact of Thrombocytopenia at 6 months after Transcatheter Aortic Valve Replacement: A Retrospective Multicenter Study

Background: Transient thrombocytopenia after transcatheter aortic valve replacement (TAVR) is a common phenomenon. Thrombocytopenia after TAVR during the perioperative period has been reported to impact prognosis. However, the impact of thrombocytopenia in the mid-term post-TAVR period is currently unknown. Methods: A retrospective observational study was conducted on 1405 patients who underwent TAVR from May 2016 to February 2023 at four institutions. Of these, 850 patients were analyzed. Patients who underwent dialysis (67), converted to an open chest surgery (8), had a Valve-in-Valve procedure (30), underwent a direct aortic approach (16), had a malignant tumor (66), and patients whose platelet levels could not be measured at 6 months after TAVR due to death or dropout were excluded from the analysis. The clinical follow-up occurred at 1, 6, and 12 months after the procedure. Laboratory testing was conducted before TAVR, during the perioperative period, 1 month post-procedure, and 6 months later. The decrease in platelet count (DPC) 6 months after TAVR was calculated by the following formula: [(Baseline platelet – 6 months platelet)/baseline platelet *100]. A receiver operating characteristics curve was plotted for all-cause mortality at 1 year and DPC at 6 months. The calculated cutoff value for the DPC at 6 months (28.68%) was utilized to classify and compare the two groups. Multivariate logistic regression models were also used to examine the association between the DPC at 6 months and all-cause mortality at 1 year. Adjusted for propensity score matching, the DPC was compared at 6 months in self-expandable and balloon-expandable prosthetic valves. Result: Of the 850 eligible patients (age: 85.5 ± 4.9 years), 31 (3.4%) died between 6 months and 1 year after TAVR. The DPC at 6 months after TAVR was 11.9 ± 22.5%. Multivariate logistic regression analysis including the DPC at 6 months, age, gender, and STS score showed that the DPC at 6 months was independently associated with all-cause mortality at 1 year (odds ratio: 1.03, 95% confidence interval: 1.005-1.046, p=0.01). After adjustment for propensity score matching, the balloon-expandable prosthetic valve had a higher rate of thrombocytopenia at 6 months (15.0% vs. 9.6%, p=0.04). Conclusion: The DPC at 6 months after TAVR may predict all-cause mortality at 1 year.

DISP-16. EXPLORING SEX-BASED DIFFERENCES IN RESPONSE TO IMMUNOTHERAPY IN GLIOBLASTOMA: A RETROSPECTIVE REVIEW

Abstract BACKGROUND The prognostic implication of sex is unclear in glioblastoma. A recent preclinical study suggested that T-cell exhaustion in males confers improved response to anti-PD1 therapy (PMID: 37378557). We conducted a retrospective study of patients with newly diagnosed (nGBM) and recurrent (rGBM) glioblastoma enrolled on immunotherapy trials at Dana-Farber Cancer Institute from 2014 to 2022 to determine whether sex influences the response to immunotherapy. METHODS Clinical, molecular, and radiographic data were collected, and their association with progression-free survival (PFS) and overall survival (OS) was evaluated using log-rank. RESULTS We evaluated 299 subjects with nGBM (172 male, 127 female) and 539 with rGBM (329 male, 210 female). In the nGBM cohort, median PFS for males vs females was 9.1 [7.2, 13.8] months vs 8.8 [6.5, 10.1] months (p=0.59) among subjects on immunotherapy trials (N=106), and 6.9 [6.1, 8.0] vs 6.5 [5.8, 8.1] months (p=0.44) in those on non-immunotherapy trials (N=193). Median OS was 18.6 [15.4, 24.0] in males vs 18.8 [15.9, 23.1] months in females (p=0.85) in immunotherapy trials and 15.6 [14.7, 17.3] vs 15.3 [13.1, 16.9] months (p=0.77) in non-immunotherapy trials. There was also no statistically significant difference in OS and PFS between sexes in the rGBM cohort: median PFS was 3.6 [3.0, 4.1] months in males vs 4.1 [3.8, 5.2] months in females and median OS was 8.4 [7.4, 9.6] vs 9.6 [8.2, 12.1] months in immunotherapy trials (N=254); median PFS was 1.8 [1.7, 2.1] vs 1.9 [1.8, 2.4] months and median OS was 8.6 [7.5, 9.6] vs 8.5 [7.3, 9.6] months in non-immunotherapy trials (N=285). CONCLUSION Sex did not have a prognostic impact on survival outcomes, regardless of the treatment modality. The impact of other clinical variables such as corticosteroid use, performance status, lymphocyte counts, and tumor burden will be reported.

NIMG-70. COMPARISON OF VOLUMETRIC AND CROSS-SECTIONAL MEASUREMENTS IN DIFFUSE MIDLINE GLIOMAS: RETHINKING RESPONSE ASSESSMENT

Abstract BACKGROUND The Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria, which are based on bidimensional or cross-sectional product (CP) measurements of tumor size, are the standard for assessing treatment response in diffuse midline glioma (DMG). This study aims to investigate the correlation between CP and volumetric measurements in progressive disease (PD) and compare their prognostic impact in pediatric patients with DMG. METHODS We retrospectively reviewed clinical and imaging data from 27 subjects with newly diagnosed DMG, encompassing 16 subjects from the PNOC003 and PNOC007 clinical trials and 11 subjects from the Children’s Hospital of Philadelphia. Tumors were segmented using a pretrained pediatric-specific autosegmentation model followed by manual revisions. Tumor volume and CP measurements were automatically derived from the outlined tumor. Cox regression analysis was used to compare the performance of CP and volumetric measurements in predicting overall survival (OS). The correlation between CP and volumetric thresholds for PD was assessed by linear regression. Comparison of survival of patients classified as PD versus non-PD by CP and volumetric measurements at 7 months post-baseline scan was performed using log-rank analysis. RESULTS Cox regression analysis demonstrated that volumetric measurements were significantly associated with OS (p=0.04), whereas CP measurements were not a significant predictor (p=0.07). An approximate 55% increase in segmented volume corresponded to a 25% increase in CP, which is the definition of PD according to RAPNO criteria (R2 = 0.71). At 7 months, volumetric classification of PD more accurately predicted survival than the CP method (p=0.06 for volumetric vs 0.14 for CP). CONCLUSION Our study showed that volumetric measurements are better predictors of survival compared to bidimensional measurements. We are extending this analysis to a larger sample size, examining survival at additional time points, and incorporating other factors influencing OS, such as treatment approaches.

NIMG-10. THE ROLE OF FIBROBLAST ACTIVATION PROTEIN IN GLIOBLASTOMA AND GLIOSARCOMA – A COMPARISON OF TISSUE, 68GA-FAPI-46 POSITRON EMISSION TOMOGRAPHY AND SURVIVAL DATA

Abstract BACKGROUND Despite their unique histological features,gliosarcomas belong to the group of glioblastomas and are treated according to the same standards. Fibroblast-activation-protein(FAP) is a component of a tumor-specific subpopulation of fibroblasts that play a critical role in tumor growth and invasion.However,the prognostic impact of FAP in glioblastoma and gliosarcoma is unclear. METHODS In a retrospective analysis,patients diagnosed with glioblastoma without sarcomatous differentiation and gliosarcoma were enrolled.Histological examination was performed using immunohistochemical FAP-staining and quantitative analysis with a standardized FAP-score.In a subset of patients,FAPI46-PET has been performed.The SUV-values are planned to be correlated with FAP-expression in the tumor tissue.Data obtained from immunohistochemical analysis and SUV-values are planned to be brought into perspective with clinically relevant prognostic factors,including survival estimates. RESULTS We enrolled 61 patients,including 13 diagnosed with gliosarcoma.Our analysis revealed that gliosarcomas exhibit significantly higher FAP-expression (median FAP-score: 3) compared to glioblastomas without sarcomatous differentiation (median FAP-score: 0.5, p&amp;lt;0.0001),where FAP was predominantly observed in the perivascular space.In gliosarcomas,FAP was also expressed by neoplastic cells.Moreover,a significant relationship was established between the immunohistochemical FAP-scores and the SUVmean and SUVpeak values on PET,suggesting that the PET tracer uptake accurately reflects the tumor’s FAP-expression.However,the differential expression of FAP suggests its potential as both a diagnostic marker and a therapeutic target.This hypothesis is further supported by the application of 68Ga-FAPI-46-PET in a 66-year-old female patient with recurrent gliosarcoma,alongside immunohistochemical analysis of tumor tissue.Both methods identified elevated FAP-expression and uptake,underscoring the feasibility of FAP as a target for nuclear medicine therapies in brain tumors. CONCLUSIONS Our study establishes a significant correlation between SUVmean/SUVpeak in 68Ga-FAPI-46 PET scans and FAP-expression in glioblastoma.Gliosarcomas express significantly more FAP than other glioblastomas. These insights suggest FAP’s potential as a theranostic target.We plan to investigate the effectiveness of FAP-specific tracers in treating recurrent gliosarcoma,aiming to open new therapeutic avenues.

PATH-32. THE PROGNOSTIC IMPACT OF CDKN2A/B HETEROZYGOUS DELETIONS IN IDH-MUTANT GLIOMA

Abstract BACKGROUND Homozygous deletions of CDKN2A/B have been shown to be a prognosticator for an unfavorable prognosis in gliomas, but the role of heterozygous CDKN2A/B deletions remains less well understood. The aim of this study was to assess the prognostic impact of CDKN2A/B heterozygous deletions in IDH-mutant low-grade astrocytoma and oligodendroglioma. METHODS Tissue samples diagnosed as astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant, 1p/19q co-deleted CNS WHO grade 2 and 3 were collected from the archive of the Institute of Neuropathology in Heidelberg. DNA methylation analysis was performed on formalin-fixed paraffin-embedded (FFPE) samples. Evaluation of the CDKN2A/B locus was performed by visual inspection of copy-number plots derived from methylation-array data for each case. Heterozygous and homozygous losses were assessed in relation to whole chromosomal or larger segmental losses and gains in the chromosomal profile. Survival probabilities were assessed using the Kaplan–Meier method. RESULTS A total of 334 low-grade glioma cases were identified. Those cases included 173 astrocytomas and 161 oligodendrogliomas. Heterozygous deletions in CDKN2A/B (37/173 in astrocytomas, 15/161 in oligodendrogliomas) did not confer worse survival outcomes compared to CDKN2A/B wildtype cases in neither low grade astrocytoma (p= 0.2556) nor oligodendroglioma (p= 0.2760), regardless of CNS WHO grade, which was further validated on a subgroup of astrocytoma, IDH mutant CNS WHO 4 cases (p= 0.1680). CONCLUSION In summary, our study suggests that heterozygous CDKN2A/B deletions do not confer worse survival rates with respect to OS and PFS in astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant, 1p/19q co-deleted CNS WHO grade 2 and 3.