Multivariate Cox Regression Analysis Research Articles

Abstract 4139177: Five-Year Clinical Outcomes of Balloon-Expandable versus Self-Expanding Transcatheter Aortic Valve Replacement in Patients with Small Aortic Annulus

Introduction: Self-expanding transcatheter aortic valves (SEV) have reportedly better hemodynamic outcomes, and similar clinical outcomes compared to balloon-expanding valves (BEV) at 1 year in patients with a small aortic annulus based on results from the SMART trial. Head-to-head comparison of long-term clinical outcomes, however, is lacking. Objectives: To compare the long-term (5 years) echocardiographic and cardiovascular outcomes in BEV versus SEV in patients with small aortic annulus undergoing transcatheter aortic valve replacement (TAVR). Methodology: The RESOLVE registry included consecutive patients who underwent TAVR and survived up to 30 days at Cedars-Sinai Medical Center with either BEV or SEV from 2015 to 2020, with clinical variables obtained from the STS/TVT registry. CT core lab analysis identified patients with a small aortic annulus (<430 mm 2 ), who were systematically followed up with clinical exams and echocardiography until December 2023. The primary outcome was a composite of all-cause mortality, stroke or transient ischemic attack, or heart failure hospitalization at 5 years. Results: Out of 1392 patients, a total of 423 met criteria for small aortic annulus (345 BEV, 78 SEV), with a median follow-up of 5 years (4-6 years). There were no significant differences in baseline sociodemographic and clinical characteristics between the BEV and SEV groups. (Figure 1) The post-TAVR invasive aortic valve mean gradient were similar in both groups [Median (IQR): BEV:3(1-5.8), SEV: 3.4(0.4-6.6), p 0.58], while echocardiographic gradients were higher in BEV group [Median (IQR): BEV:12 (9-15), SEV:8(6-11), p<0.001)].There was no significant difference in primary outcome at 5 years in Cox multivariable regression analysis (HR:1.21, 95% CI 0.81-1.82, p 0.33) (Figure 2). There were no significant differences in other clinical endpoints at 5 years, although patients with SEV had lower echocardiographic gradients and higher indexed effective orifice area. (Figure 2-3) Conclusion: Post-TAVR invasive aortic valve gradients were similar between BEV and SEV, despite higher echocardiographic transaortic gradients in BEV patients. We found no significant difference in 5-year clinical outcomes between patients who received TAVR with BEV or SEV.

Abstract 4137900: Differences in Echocardiographic Findings Between Epicardial Vasospastic Angina Phenotypes Affect Response to Medical Therapy

Background: The phenotype of epicardial vasospasm is classified as focal or diffuse. However, its echocardiographic characteristics are unknown. Furthermore, patients with diffuse vasospasms have poorer responses to medical therapy than patients with focal spasms because of more extensive areas of endothelial dysfunction. We hypothesized that there are differences in echocardiographic findings between the patients with diffuse and focal vasospasm, which might affect response to medical therapy. Methods: The present study was a single-center retrospective cohort study that included 77 consecutive patients diagnosed with vasospastic angina (VSA) undergoing coronary spasm provocation test using acetylcholine from 2014 to 2024. The patients with a history of cardiomyopathy and significant obstructive coronary artery disease were excluded. Diffuse VSA was defined as vasospasm in 2≧ adjacent coronary segments, and focal VSA was defined as vasospasm in one isolated coronary segment. Patients were divided into diffuse VSA group (n=45) and focal VSA group (n=32). Left ventricular function was assessed using 2D speckle tracking echocardiography. After the diagnosis of VSA and the administration of medical treatment for VSA, an emergency room (ER) visit with a chest pain attack was recorded as the event of poor response to medical therapy. Results: There was no significant difference in the follow-up period and baseline characteristics (Table). LVEF was similar between the two groups (63.1±5.8% vs. 62.9±7.6%, p =0.87). In contrast, the left ventricular global longitudinal strain (LV-GLS) was significantly lower in the diffuse VSA group than in the focal VSA group (17.4±2.8% vs. 20.2±2.4% p <0.001). There is no difference in medical therapy for VSA (Table). Observation of ER visits with a chest was more frequent in the diffuse VSA group [diffuse VSA group (20/45, 44.4%) vs. focal VSA group (3/29, 9.3%), p <0.001]. Kaplan-Meier curves showed that the diffuse VSA group had a higher cumulative rate of ER visits with a chest pain attack (Log-rank p <0.001). On multivariable Cox regression analysis, diffuse VSA (HR=4.2, 95% CI: 1.10-16.06, p =0.030) and low LV-GLS (HR =1.16, 95%CI: 1.01-1.34, p =0.031) were an independent risk factor for poor response to medical therapy. Conclusion: Patients with diffuse VSA had lower LV-GLS than patients with focal VSA. Moreover, diffuse VSA and lower LV-GLS were associated with poor response to medical therapy after diagnosis of VSA.

Prognostic significance of collagen content in solitary fibrous tumors of the central nervous system

PurposeWe aimed to explore the prognostic significance of collagen content in solitary fibrous tumors (SFTs) of the central nervous system (CNS) and preliminarily investigate its relationship with magnetic resonance imaging (MRI) features of SFTs.MethodsCollagen content was identified using Masson’s trichrome staining, and quantitatively assessed. Radiomic methods were applied to extract quantitative MRI features of SFTs, which were then analyzed in relation to collagen content.ResultsThe collagen content in CNS SFTs was categorized into high- and low-content groups, with a cutoff value of 6%. Survival analysis indicated a positive correlation between collagen content and overall survival (OS). In multivariate Cox regression analysis, incorporating factors such as mitosis, necrosis, Ki67, and collagen content and other indicators, collagen content emerged as an independent prognostic factor. Collagen content demonstrated a negative correlation with tumor histological phenotype, Ki67, WHO grade, mitosis, necrosis, and brain invasion. Additionally, the signal intensity of SFTs on T2-weighted imaging (T2WI) decreased with increasing collagen content. Radiomics analysis identified 1,702 features from each patient’s region of interest, with 12 features showing significant differences between the high and low collagen content groups. Among the quantitative parameters and radiomic models, the combined T1- and T2WI models exhibited the highest diagnostic performance.ConclusionThese findings suggest that collagen content is an independent prognostic risk factor for OS. Furthermore, combined radiomic models based on T1-and T2WI sequences may offer a more comprehensive, objective, and accurate assessment of collagen content in CNS SFTs.

Abstract 4112652: Impact of metabolic overweight/obesity phenotypes on clinical outcomes of patients with resectable non-small cell lung cancer in an Asian population

Background: Metabolic syndrome and obesity are known to increase the incidence of lung cancer. We investigated the association between metabolic health and overweight/obesity phenotypes and clinical outcomes in patients with resectable non-small cell lung cancer (NSCLC). Methods: This large retrospective cohort study included adult patients who underwent curative upfront surgery for their stage IA-IIIB NSCLC at a tertiary university hospital from January 2010 to December 2020. They were classified into four phenotypes based on the combination of metabolic health status and body mass index categories: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight/obesity (MHO), metabolically unhealthy overweight/obesity (MUO). The primary outcomes were disease recurrence and death. Results: Of the 1,513 patients (342 with MHNW, 585 with MUNW, 122 with MHO, and 464 with MUO), patients with the phenotype of MHO were less likely to experience recurrence (MHO [13.1%] vs. MHNW [16.1%] vs. MUNW [22.9%] vs. MUO [19.2%], p = 0.018) and death (MHO [15.6%] vs. MHNW [24.6%] vs. MHUW [31.3%] vs. MUO [24.8%], p < 0.001) compared to those with other 3 phenotypes. Similar results were observed in Kaplan-Meier curves for the primary outcomes according to the four phenotypes (all log-rank P < 0.05). In multivariate Cox regression analyses, both MHO and MUO phenotypes did not increase the risk of recurrence compared to the MHNW phenotype and were associated with improved survival (MHO: adjusted hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.36-0.98, p = 0.040; MUO: adjusted HR 0.76, 95% CI 0.60-0.96, p = 0.022). Conclusions: After curative resection for NSCLC, regardless of metabolic health, patients with overweight/obesity were not at an increased risk of recurrence and paradoxically, had favorable overall survival.

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<0.001) and estimated right atrial pressure by echocardiography (eRAP) (HR 4.22, 95%CI 1.42-12.5, p<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 < 0.08 had a significantly poorer prognosis (log-rank p<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.

Predictive and prognostic factors in patients with Anaplastic Lymphoma Kinase: rearranged early-stage lung adenocarcinoma.

This study aimed to evaluate the predictive and prognostic factors in clinical stage I, ALK-rearranged lung adenocarcinoma following radical surgery. Additionally, it sought to compare these factors with an external cohort of ALK wild-type patients. A multicentric, retrospective, case control analysis was conducted on patients with clinical T1-2 N0 ALK-rearranged lung adenocarcinoma who underwent anatomical resection and radical lymphadenectomy. Data were collected from five high-volume oncological centers. An external cohort of ALK wild type patients was also analyzed for comparison. Survival analyses were performed using the Kaplan-Meier method, and multivariable Cox regression analysis was used to identify prognostic factors. From January 2016 to December 2022, 63 patients with ALK-rearranged lung adenocarcinoma were included. High-grade tumors (G3) significantly associated with upstaging (OR = 3.904, p = 0.04). DFS and OS were significantly improved in upstaged patients receiving adjuvant treatment (HR = 0.18, p = 0.0042; HR = 0.24, p = 0.0004, respectively). The solid or micropapillary histological subtypes were independently associated with worse DFS (HR = 3.41, p = 0.022). Comparison with 435 ALK WT patients showed worse DFS in the ALK-rearranged group (HR = 2.09, p = 0.0003). ALK-rearranged patients had higher rates of nodal upstaging, systemic, and brain recurrences. Clinical T1-2 N0 ALK-rearranged lung adenocarcinoma is an aggressive disease with a specific tropism for lymph nodes and the brain. High-grade tumors are predictive of nodal upstaging. Adjuvant treatment significantly improves DFS and OS in upstaged patients, highlighting the need for personalized preoperative staging and post-surgical management in this cohort.

RNF213 p.Arg4810Lys Variant Is Associated with Higher Stenosis Progression in Asymptomatic Intracranial Artery Stenosis.

Intracranial artery stenosis (ICAS) is a significant contributor to ischemic stroke, with the RNF213 p.Arg4810Lys variant identified as a related genetic factor. We explored the clinical outcomes of the RNF213 genotype in patients with asymptomatic ICAS. Between November 2011 and March 2019, 139 patients with asymptomatic ICAS were enrolled in this study. Genotyping for RNF213 p.Arg4810Lys was performed using Sanger sequencing. A comprehensive analysis was conducted to compare the RNF213 genotype with background characteristics and clinical outcomes such as ipsilateral ischemic cerebrovascular events and stenosis progression. RNF213 p.Arg4810Lys was found in 25% of cases, revealing distinct clinical features between carriers and non-carriers. The incidence of ipsilateral ischemic cerebrovascular events was 4.3% (6/139 cases), and stenosis progression was observed in 13% (18/139 cases) during a mean follow-up period of 58months. Stenosis progression rates were notably higher in the RNF213 variant group (25.7%; 9/35 cases) than in the RNF213 wild-type group (8.7%; 9/104 cases). Cumulative stenosis progression rate was significantly higher in the RNF213 variant group than in the RNF213 wild-type group (log-rank test, P = 0.0004). Multivariate Cox regression analysis indicated a significant association between the RNF213 p.Arg4810Lys variant and an increased risk of stenosis progression (P = 0.03, odds ratio 3.2; 95% confidence interval, 1.1-9.0). The RNF213 p.Arg4810Lys variant exhibits clinical disparities in asymptomatic ICAS and is notably linked to a heightened risk of stenosis progression. These results suggest a distinct difference in the vascular stenosis mechanism associated with this variant, warranting further investigation into its clinical implications and potential mechanistic insights.

Abstract Su1205: The Effect of Targeted Temperature Management on Five-Year Mortality in Comatose Out-of-Hospital Cardiac Arrest Survivors: A Real-World Experience

Background: Hypothermia-Induced Targeted Temperature Management (TTM) is a neuroprotective treatment after the return of spontaneous circulation (ROSC) in comatose survivors of out-of-hospital cardiac arrest (OHCA). However, its effectiveness in all patient subpopulations is debated. While short-term survival has been well studied, the impact of TTM on long-term survival is still unknown. Methods: In a prospective cohort study, 98 comatose survivors of non-traumatic OHCA were recruited from four tertiary-level hospitals in Buffalo, Western New York and followed up for five years. Patients with active cancer, infection, cardiac pathology or surgery in three-month prior to presentation, were excluded. Cardiac arrest characteristics, demographics, comorbidities, and therapeutic interventions were recorded. According to TTM protocols, a target body temperature of 33°C was reached and maintained for 24 hours using either an intravascular cooling catheter or a surface cooling system. This was followed by gradual controlled rewarming over 12-24 hours to normothermia. Factors associated with the receipt of TTM were determined. The effect of TTM on five-year survival was studied using cox-regression analysis. Results: Among comatose patients with mean age of 60.1±14.9 years, 49% received TTM. Females were significantly less likely to receive TTM (35.1% vs 59.3%, p=0.021). In TTM group, the time to ROSC was significantly longer: median [IQR] 14.5 mins (5-19.7) vs 20 mins (12-27), p=0.018. TTM group was more likely to have a history of coronary artery disease (CAD) (12.5% vs 35.4%, p=0.009). Overall, 5-year mortality did not differ significantly between TTM vs. non-TTM: 72.9% vs 66.0%, (HR: 1.134, 95% CI: 0.705-1.826, p=0.603) in univariate and multivariate Cox-regression analysis (Table 1). Conclusion: While females are less likely to receive TTM treatment, TTM is more likely to be used in patients with a longer time to ROSC and a history of CAD. The overall five-year survival remains high in both treatment groups in all eligible patients, as well as in shockable and non-shockable rhythm groups studied separately. Larger cohort studies are needed to determine the patients who may benefit most from TTM.

Abstract 4117640: Thirty-Year Prevalence and Prognosis of the Cardiovascular-Kidney-Metabolic Syndrome in U.S. Females and Males

Background: The American Heart Association recently published guidelines on how to clinically identify and categorize individuals with cardiovascular-kidney-metabolic (CKM) syndrome. The extent to which CKM syndrome prevalence and prognosis differ by sex remain unknown. This study aimed to examine the impact of sex on trends in prevalence over 30 years and long-term prognosis of the CKM syndrome in the US. Methods: We analyzed nationally representative NHANES 1988-2018 data collected from 33,868 US adults (age ≥20 years) who were under surveillance for all-cause mortality through December 31, 2019. We examined sex-specific prevalence of CKM syndrome, and sex-specific CKM associations with all-cause mortality. Results: Of the 33,868 adults studied, the mean±SD age was 48.4±18.3 years with 52% female and 56% non-White. Overall prevalence of CKM syndrome increased steadily from 1988 to 2018 in both sexes, with a larger temporal rise in prevalent Stage 3 CKM seen for males (from 18.9% to 22.4%) compared to females (from 13.9% to 15.2%) ( Figure 1 ). Over a median follow-up of 13.3 years, there were 8745 deaths. In multivariable cox-regression analysis, worsening CKM severity was associated with all-cause mortality (P<0.001 for both sexes), with greater magnitudes of risk seen in females (HR=1.24 to 3.33) compared to males (HR=0.85 to 2.60) across all stages (LRT χ 2 =19.0, P interaction <0.001); results were similar for cardiovascular mortality (LRT χ 2 =22.3, P interaction <0.001) ( Table 1 ). Conclusions: Females, compared with males, exhibited a lower prevalence of CKM stage 3 but experienced excess mortality risk across the spectrum of multi-system CKM dysfunction. These findings underscore the importance of identifying mechanisms underlying joint cardiovascular, renal, and metabolic systems pathophysiology to close a potentially widening sex disparities gap in multi-organ disease risk.

A prognostic nomogram for patients with III-IV nasopharyngeal carcinoma based on dynamic changes in the inflammatory and nutrition index.

The purpose of the study was to explore the value of dynamic changes in inflammatory and nutritional index after comprehensive treatment in patients with stage III-IVA nasopharyngeal carcinoma (NPC). A prognostic model was also established and validated for progression-free survival (PFS) of patients. We retrospectively selected 279 NPC patients with stage III-IVA. Their general clinical data and hematological index were collected and then calculated the changes during treatment. X-tile software was used to determine the optimal cut-off value. COX regression, Lasso method, and Boruta method were used to variable selection and model establishment. Using the bootstrap internal validation method, concordance index (C-index), calibration plot, and Kaplan-Meier curves were used to evaluate the model. To test the prognostic value of the model, we have also evaluated the performance of the nomogram against a conventional tumor metastasis staging system (TNM). Multivariable COX regression analysis demonstrated that clinical staging, delta lymphocyte, delta monocyte, delta albumin, delta platelet-to-lymphocyte ratio and delta systemic immune inflammation index were related to the PFS of NPC patients. The C-index of the model was 0.712, and the calibration curve indicated that the model had good consistency. The C-index of the TNM staging system was 0.597, which was considerably lower compared to our model (P = 0.015). We demonstrated the predictive value of dynamic changes in inflammatory and nutritional indices for the prognosis of NPC by successfully establishing and validating a prognostic model for predicting 1- and 3-year PFS after comprehensive treatment in patients with stage III-IVA NPC.

Abstract 4135327: Long-term Bleeding Events after Percutaneous Coronary Intervention in Patients with Malignancy with and without Anticoagulant Therapy

Background: With the aging population, the prevalence of malignancies in patients undergoing percutaneous coronary intervention (PCI) is increasing. Active malignancy is increasingly recognized as a significant contributor to high bleeding risks. In cases where anticoagulant (AC) therapy is required, it becomes crucial to determine which is the optimal choice for cancer patients, direct oral anticoagulants (DOACs) or warfarin. The aim of this study was to investigate long-term bleeding events in patients with malignancy undergoing PCI. Methods: CLIDAS (Clinical Deep Data Accumulation System) is a multicenter database with 7 tertiary medical hospitals in Japan. This retrospective analysis using CLIDAS database included 6838 patients who underwent PCI during April 2014 and March 2020 and also who have completed 3-year follow-up were divided into two groups; No malignancy group (n=6155) and malignancy group (n=683). Malignancy was defined as patients with treatment history of malignancy. Furthermore, these patients were categorized into six groups based on the presence of malignancy and the type of AC therapy; 1) No malignancy without AC (n=5369), 2) No malignancy with DOAC (n=294), 3) No malignancy with warfarin (n=492), 4) Malignancy without AC (n=586), 5) Malignancy with DOAC (n=44), and 6) Malignancy with warfarin (n=53). The primary outcome was the incidence of bleeding events, defined according to the Global Use of Streptokinase and t-PA for Occluded Coronary Arteries classification of moderate and severe bleeding. Results: During the 3-year follow-up period, 260 (3.8%) patients experienced major bleeding events after PCI. Among these patients, 180 (3.4%) were in group 1, 9 (3.1%) in group 2, 33 (6.7%) in group 3, 27 (4.6%) in group 4, 2 (4.5%) in group 5, and 9 (17.0%) in group 6. Multivariate Cox regression analysis showed that patients in the malignancy group had a significantly higher rate of bleeding events (HR, 1.50; 95% CI, 1.03-2.18). Furthermore, only the malignancy with warfarin group showed a significantly higher rate of bleeding events compared to the no malignancy without AC group (HR, 4.03; 95% CI, 1.94-8.37). Conclusions: Patients with malignancies receiving warfarin were associated with a higher risk of bleeding events. DOACs may be a safer alternative to warfarin in reducing bleeding risk in this population.

Abstract 4145842: The Incidence, Predictors and Impact of 30-day Readmission of Takotsubo Cardiomyopathy Hospitalization: A Retrospective Nationwide Analysis

Objective: This study aimed to describe the recent readmission and mortality rates of unplanned 30-day all cause readmission after takotsubo cardiomyopathy hospitalization. Methods: We conducted an analysis of the 2020 Nationwide Readmission Database. Using the ICD-10 code, we identified hospitalizations for takotsubo cardiomyopathy. We excluded hospitalizations for age<18years and planned or elective readmissions. To compare baseline characteristics between readmissions and index hospitalizations, Pearson χ2 tests were employed. We utilized multivariate Cox regression analyses to identify independent predictors of readmissions. Results: A total of 7554 patients were hospitalized for index admission for takotsubo cardiomyopathy, and 633 of them were readmitted. The 30-day all-cause readmission rate was 8.5% while specific takotsubo readmission rate was 0.4%. The mortality rate in the index admission was 1.9% and 5.5% in readmitted patients. The mean age of index admission was 67.6years vs 70.7 years in readmission, about 89.0% were female in index admission vs 85.0% in readmission cohorts. The most common reasons for readmission were hypertensive heart disease with heart failure, hypertensive heart disease and chronic kidney disease with heart failure, takotsubo syndrome, sepsis, NSTEMI, COPD exacerbation, acute kidney failure, pneumonia, atrial fibrillation. Readmissions had more acute kidney injury (20.6% vs 11.3%, p-value <0.001) and atrial fibrillation (23.0% vs 13.0%, p <0.001) compared to the index admission, however the index admission had more ventricular tachycardia (4.6% versus 1.8%, p=0.02) compared to readmission cohorts. Readmission had longer length of hospital stay (4.9 days vs 3.7 days, p< 0.001), but less mean total hospital charge of (US$51039 vs US$60617, P =0.008). Older age, acute renal failure, pulmonary disease, coronary dissection, longer length of hospital stays and transfer to rehabilitation facility after discharge were identified as statistically significant predictors of readmissions. Conclusion: About one in twelve patients hospitalized with takotsubo cardiomyopathy were readmitted within 30days. Readmissions had a higher mortality rate; acute renal failure, pulmonary disease, coronary dissection were notable reasons for readmission. Understanding the predictors for readmission highlighted in this study would enable clinicians implement preventive strategies to improve the rate of takotsubo cardiomyopathy readmission

NCOG-11. FACTORS PREDICTING SPEECH AND GAIT RECOVERY IN CHILDREN WITH POST-OPERATIVE POSTERIOR FOSSA SYNDROME (PFS)

Abstract Posterior fossa syndrome/cerebellar mutism syndrome is a surgical complication of posterior fossa tumor resection, especially midline tumors. Initially thought to involve complete mutism, PFS is now recognized as a complex syndrome involving loss of language (complete [PFS1] and incomplete [PFS2]). Additional symptoms include apraxia, movement disorder, motor and coordination deficits, and emotional lability. The aim of this study was to identify factors that influence delayed speech and independent gait recovery in children with PFS. We prospectively studied 73 children ≥3 years of age with medulloblastoma who developed PFS (SJMB12, NCT01878617). Enrolled children received standardized neurologic examinations and serial imaging before, during and up to five years after completion of therapy. Neurological examinations included scale for assessment and rating of ataxia (SARA), CTCAE grading of neurologic deficits, and severity of injury to the superior cerebellar peduncles (SCP) on post-operative MRI. Median time to speech recovery was 1.4 months (range 0.3-14.3); 81% had return of speech at 3 months and 97% at 12 months. On multivariable Cox regression analysis, complete mutism (HR 0.17, p<0.0001) and inability to sit (HR 0.40, p=0.001) were associated with delayed speech return. Independent ambulation was regained by 80.8% at a median of 2.3 (range 0.3-71.3) months. 70% had a return of ambulation at 12 months and 77% at 24 months. On multivariable Cox regression analysis, complete mutism (HR 0.32, p=0.016), inability to sit (HR 0.30, p=0.002), SARA score (HR 0.94, p=0.002), and right SCP injury (HR 0.47, p=0.014) were significantly associated with delayed return of ambulation. Presence of mutism, inability to sit unassisted, higher SARA score, and right SCP injury at the time of PFS diagnosis are associated with time to recovery of speech/language and ambulation. Our findings have prognostic implications for families and to help identify children in need of more intensive interventions.

Personalized MRD Assessment in Peri-surgical ctDNA for Prognostic Prediction in Hepatocellular Carcinoma.

Detecting residual disease is a critical clinical requirement in the peri-surgical management of patients with resectable hepatocellular carcinoma (HCC). Previous studies focused on specific genomic regions exhibiting limited sensitivity and failed to meet the minimal residual disease (MRD) testing threshold. We introduce a next-generation sequencing (NGS) based assay, informed by baseline samples, facilitating MRD detection in hepatectomized HCC patients and offering prognostic predictions. This study involved 88 HCC patients who underwent surgical resections January 2016 to May 2016 in Zhongshan Hospital Fudan University. Tumor and normal tissue samples were collected during surgery, while plasma samples were obtained both before surgery and up to seven days post-surgery. Using an NGS-based personalized circulating tumor DNA assay, we analyzed MRD in both pre-surgical and post-surgical blood samples and the correlation with prognosis. With a median follow-up period of 80.7 months, our findings demonstrated significant correlations between pre-surgical ctDNA tumor fractions, post-surgical plasma MRD status, and both recurrence-free survival (RFS) and overall survival (OS). Post-surgical MRD status emerged as the most significant risk factor for cancer recurrence (HR=2.17, 95% CI: 1.09-4.30, p=0.027) compared to other clinical characteristics in multivariate Cox regression analysis. Notably, MRD status showed potential as a prognostic indicator among clinically low-recurrent-risk patients, such as those with BCLC stage 0-A, CNLC stage I-II. Evaluating personalized MRD provided crucial prognostic insights into RFS and OS. It efficiently identified patients at high risk of recurrence, even among those initially perceived as low-risk cases.

PSTAT3 Expression is Increased in Advanced Prostate Cancer in Post-Initiation of Androgen Deprivation Therapy.

The transcription factor Signal Transducer and Activator of Transcription 3 (STAT3) plays a role in carcinogenesis and is involved in processes, such as proliferation, differentiation, drug resistance and immunosuppression. STAT3 can be activated by phosphorylation of tyrosine at position 705 (pSTAT3Tyr705) or serine at 727 (pSTAT3Ser727). High expression levels of pSTAT3 are implicated in advanced stages of prostate cancer (PCa) and are known to interact with the androgen receptor signaling pathway. However, not much is known about how androgen deprivation therapy (ADT) in advanced disease affects pSTAT3 expression. The aim of this study was to determine the influence of ADT on pSTAT3 expression in PCa tissue. The study cohort came from a PCa tissue microarray resource containing prostate specimens from patients before and post-initiation of ADT. Tissue samples from 111 patients were immunostained for pSTAT3Tyr705 and pSTAT3Ser727. H-score was used to evaluate the intensity and the percentage of pSTAT3 expression in malignant epithelial and stromal compartments. Univariate and multivariable Cox regression analyses were used to assess pSTAT3Tyr705 and pSTAT3Ser727 as biomarkers of oncological outcome in patients undergoing ADT. Post-ADT PCa samples demonstrated increased nuclear and cytoplasmic levels of pSTAT3Ser727 in the stroma compared to pre-ADT samples, whereas pSTAT3Tyr705 expression was increased significantly in both stromal and malignant epithelial compartments except for stromal cytoplasm. High cytoplasmic pSTAT3Ser727 in stromal compartments correlated with reduced overall survival, shorter time to castration-resistant PCa development, and decreased metastasis-free survival. An increase in nuclear and cytoplasmic pSTAT3Ser727 expression within the stromal compartment of post-ADT samples corresponded to a shorter time to CRPC development, which was not observed for pSTAT3Tyr705. Multivariable survival analysis using Cox's regression identified that high cytoplasmic pSTAT3Ser727 expression in the stroma of post-ADT samples and pT3 or pT4-stage were associated with worse overall survival and 5-year metastasis-free survival (MFS). This study presents novel insights into the impact of ADT on the expression levels of pSTAT3Tyr705 and pSTAT3Ser727 in PCa. Cytoplasmic pSTAT3Ser727 status of cancer-associated stromal cells in post-ADT samples may serve as an independent prognostic marker for OS and 5-year MFS, identifying prostate cancer patients prone to developing resistance to ADT.

Sex differences in prognosis of primary bone cancer: a propensity score-matched study

Abstract Objectives Sex differences in survival in primary bone cancer have not been fully explored. Hence, this study was conducted to investigate the impact of sex on survival outcomes in patients with primary bone cancer. Methods The Surveillance, Epidemiology, and End Results (SEER)-17 database was used to identify patients with primary bone cancer. One-to-one propensity score matching (PSM) was employed to balance baseline characteristics. Kaplan-Meier curves and log-rank tests were used to evaluate differences in cancer-specific survival (CSS) and overall survival (OS) between sexes. Multivariate Cox regression analysis was performed to verify the independent effect of sex on survival, and sensitivity analysis was performed to determine the robustness of the results. Results A total of 8,791 patients were included, with 4,928 males (56.1 %) and 3,863 females (43.9 %), and a median follow-up time of 38 months. After PSM, 3,812 males and 3,812 females were included in the study, with balanced baseline characteristics between the groups. Post-PSM, females show significantly better CSS (HR=0.88, 95 % CI, 0.81–0.96, p=0.004) and OS (HR=0.87, 95 % CI, 0.81–0.94, p<0.001) compared to males. In multivariable Cox regression, the female sex was identified as an independent protective factor for both CSS (HR=0.86, 95 % CI, 0.79–0.94, p<0.001) and OS (HR=0.83, 95 % CI, 0.77–0.89, p<0.001). Conclusions Based on the analysis of SEER data with a large sample size, this study revealed that female patients with primary bone cancer have significantly better survival compared to males.

EPID-32. ELEVATED SERUM IGE IS LINKED TO IMPROVED GLIOBLASTOMA SURVIVAL, PARTICULARLY AMONG FEMALES

Abstract Prior epidemiological research shows a correlation between serum immunoglobulin E (IgE) levels and decreased risk of glioma. However, the relationship between IgE and the prognosis of glioma remains poorly understood. This study seeks to investigate how factors such as sex, tumor subtype, and IgE class influence the association of serum IgE levels with both glioma risk and survival outcomes. METHODS- In this investigation, we conducted a case-control study utilizing participants enrolled in the UCSF Adult Glioma Study from 1997 to 2010. We measured serum IgE levels for total, respiratory, and food allergy in adults diagnosed with glioma (n=1,696), and controls (n=1,135) matched based on age, sex, and race/ethnicity. Logistic regression, adjusted for patient demographics, was employed to evaluate the correlation between IgE levels and glioma risk. Multivariable Cox regression, adjusted for patient-specific and tumor-specific factors, was utilized to compare survival outcomes between the elevated and normal IgE groups. RESULTS- Increased levels of total IgE were linked to a decreased risk of both IDH wildtype (OR=0.65, 95% CI: 0.54-0.78) and IDH mutant glioma (OR=0.65, 95% CI: 0.50-0.85). In multivariable Cox regression analysis, heightened respiratory IgE levels were associated with enhanced survival among individuals with IDH wildtype glioma (HR=0.78, 95% CI: 0.67-0.91). Notably, this improved survival was more pronounced in females (HR=0.71, 95% CI: 0.53-0.96) compared to males (HR=0.80, 95% CI: 0.66-0.97), resulting in median survival improvements of 6.2 months (P<.001) and 1.6 months (P=0.003), respectively. CONCLUSION- Increased levels of serum IgE were associated with reduced risk of glioma overall, and improved prognosis for IDH wildtype glioma, which was particularly strong in females. These findings hint at potential sexual dimorphism in the antitumor activity of IgE-mediated immune responses, suggest an important role for IgE assessment in glioblastoma clinical trial design, and provide justification for investigations into IgE-based therapeutics.

CNSC-16. ASSOCIATION BETWEEN RESTING-STATE-NETWORK FUNCTIONAL CONNECTIVITY AND SURVIVAL IN RECURRENT GLIOMAS DIAGNOSED USING FET PET

Abstract BACKGROUND Functional connectivity between glioma-infiltrated brain tissue and remote cortical regions has been linked to overall survival (OS) in patients with newly diagnosed glioblastoma. We studied the association of functional connectivity between tumor and resting-state networks and OS in patients with recurrent gliomas. PATIENTS AND METHODS The study included 82 patients (26-81 years; median ECOG performance score, 0) with recurrent gliomas (grade 4 glioblastoma, n=57; grade 3 and 4 astrocytoma, n=12; grade 2 and 3 oligodendroglioma, n=13) who had undergone first-line therapy. Diagnosis of recurrence was confirmed by amino acid PET using the tracer O-(2-[18F]-fluoroethyl)-L-tyrosine (FET). FET PET and resting-state functional MRI were simultaneously acquired on a 3T hybrid PET/MR scanner. We performed a seed-based dual regression analysis to determine the functional connectivity between metabolically active tumors and seven canonical resting state networks. RESULTS Average functional connectivity was highest in oligodendrogliomas (z-score, 6.9±1.9) and was inversely related to the tumor grade (p=0.031). Univariate Cox regression analysis revealed a significant (p<0.05) positive association between OS and tumor connectivity with the visual, somatomotor, and dorsal attention networks. Subsequent stepwise multivariate Cox regression analysis refined this association to the dorsal attention network alone (HR, 0.88; 95% CI, 0.80-0.97; p=0.007). Patients with the highest functional connectivity (z-score>8.3, n=21) had a median OS of 31.4 months, while those with the lowest functional connectivity (z-score<4.3, n=21) had 10.6 months. Functional connectivity between tumors and the dorsal attention network showed an independent association with OS (HR, 0.90; 95% CI, 0.81-0.99; p=0.033) in a multivariate model, including various prognostic factors. CONCLUSION Recurrent gliomas exhibit significant functional connectivity to most of the major known resting-state networks, highest in oligodendrogliomas. The data suggest that high functional connectivity between the tumor and the dorsal attention network is an independent prognostic factor for improved OS.

Analysis of METTL14 expression in pancreatic cancer and adjacent tissues and its prognostic value for patient outcomes.

This study aims to analyze the differential expression of METTL14 in pancreatic cancer (PC) tissues and adjacent normal tissues, and its correlation with clinical outcomes. According to the inclusion and exclusion criteria, a total of 80 patients diagnosed in our hospital from January 2021 to January 2023 were chosen as research subjects. RTQ-PCR has detected the mRNA level expression of METTL14 in cancer and para-cancerous tissues. Immunohistochemistry was used to detect the protein expression of METTL14 in cancer and para-cancerous tissues. To compare the relationship between METTL14 expression and clinicopathological parameters in different PC patients. Kaplan-Meier survival analysis of the relationship between METTL14 expression in PC tissues and patient survival prognosis. The Multifactor COX model evaluates factors affecting the prognosis of PC. The expression level of METTL14 mRNA in PC tissues was 5.51 ± 0.35 (kDa), and the positive rate of METTL14 protein expression in PC tissues of all patients was 73.75 (59/80). Tumor location (P = 0.012), tumor differentiation degree (P = 0.028), tumor AJCC stage (P = 0.000), and lymph node metastasis (P = 0.000) were significantly related to the positive rate of METTL14 protein expression in PC tissue. Follow-up results showed that among 80 patients, 63 died. The three-year survival rate of the METTL14 positive group was 13.56% (8/59), and the three-year survival rate of the negative group was 42.86% (9/21). The difference in the three-year survival rate between METTL14 positive and negative expression groups was statistically significant (P = 0.031). Multivariate COX regression analysis results showed that METTL14 was positive (OR 2.797, 95% CI 1.233-5.877), tumor AJCC stage II-III (OR 1.628, 95% CI 1.435-3.859) and lymph node metastasis (OR 1.733, 95% CI 1.122-2.372) were substantive risk factors for poor prognosis in patients with PC. METTL14 expression increases in PC tissue, which is related to tumor AJCC stage, tumor differentiation, and lymph node metastasis, and can be evaluated in the survival prognosis of patients with PC.

A nomogram model to predict recurrence of early-onset endometrial cancer after resection based on clinical parameters and immunohistochemical markers: a multi-institutional study

ObjectiveThis study aimed to investigate the prognosis value of the clinical parameters and immunohistochemical markers of patients with early-onset endometrial cancer (EC) and establish a nomogram to accurately predict recurrence-free survival (RFS) of early-onset EC after resection.MethodsA training dataset containing 458 patients and an independent testing dataset consisting of 170 patients were employed in this retrospective study. The independent risk factors related to RFS were confirmed using Cox regression models. A nomogram model was established to predict RFS at 3 and 5 years post-hysterectomy. The C-index, area under the curve (AUC) of the receiver operating characteristic (ROC) curve, and calibration curve were calculated to assess the predictive accuracy of the nomogram.ResultsIn all early-onset EC patients, more than half (368/628, 58.6%) were diagnosed in the age range of 45-49 years. Meanwhile, the recurrence rate of early-onset EC is approximately 10.8%. Multivariate Cox regression analyses showed that histological subtype, FIGO stage, myometrial invasion, lymphovascular space invasion (LVSI), P53 expression, and MMR status were independent prognostic factors related to RFS (all P < 0.05) and established the nomogram predicting 3- and 5-year RFS. The C-index and calibration curves of the nomogram demonstrated a close correlation between predicted and actual RFS. Patients were divided into high- and low-risk groups according to the model of RFS.ConclusionsCombining clinical parameters and immunohistochemical markers, we developed a robust nomogram to predict RFS after surgery for early-onset EC patients. This nomogram can predict prognosis well and guide treatment decisions.