Kaplan-Meier Log Rank Research Articles

Impact of atrial fibrillation on mortality and non-fatal clinical outcomes in 28 492 patients who had undergone open-heart aortic versus mitral valve surgery: a statewide population-linkage study

Abstract Background Postoperative atrial fibrillation (AF) is common after cardiac surgery and has been associated with increased mortality and morbidity. Few studies have defined the impact of AF status (New-AF versus Prior-AF) on clinical outcomes during long-term follow-up and compared AF-related clinical outcomes between patients who had undergone isolated aortic valve surgery (AVSx) or mitral valve surgery (MVSx). Purpose This study aims to examine the impact of AF status on clinical outcomes in patients who had undergone AVSx versus MVSx using a statewide-population administrative database. Methods Patients who had open-heart cardiac valve surgery (1 January 2003 to 31 March 2021) identified from the Admitted-Patient-Data-Collection database in an Australian state, were stratified by AF status (No-AF vs New-AF vs Prior-AF during index admission for valve surgery) and followed up to 31 March 2022. A linkage look-back to year-2001 was performed to identify prior-AF history. Kaplan-Meier and multivariable Cox regression were performed to assess the impact of AF status on all-cause mortality. Fine-Gray competing risk analysis to account for the competing death events was used to assess non-fatal clinical outcomes. Results The overall cohort comprised 28 492 patients (median age 71.6yrs [interquartile range (IQR) 62.7–78.3yrs; 65.6% males): AVSx, n=18949; MVSx, n=9543 (Table 1). During a median follow-up of 6.6yrs (3.42–10.5yrs), Prior-AF and New-AF patients had significantly higher all-cause mortality (AVSx – Prior-AF: 1771 (57.9%) vs New-AF: 2854 (41.5%) vs No-AF: 2961 (32.8%); MVSx – Prior-AF: 1126 (41.0%) vs New-AF: 1034 (29.8%) vs No-AF: 747 (22.4%) (both Kaplan-Meier logrank P<0.001). After adjusting for differences in baseline characteristics and admission year-groups, in the AVSx subgroup, both new-AF and prior-AF were independently associated with all-cause mortality (aHR=1.16, 95%CI=1.10–1.22; aHR=1.69, 95%CI=1.59–1.79 respectively, both P<0.001) compared to no-AF patients. In the MVSx subgroup, only prior-AF was associated with increased risk of all-cause mortality (aHR=1.47, 95% CI=1.33–1.61, P<0.001). Competing risk analyses showed higher rehospitalisation rates for AF and congestive cardiac failure for new-AF and prior-AF groups compared to No-AF patients after both AVSx and MVSx, whereas the rehospitalisation rate for ischemic stroke was only significantly higher in the AVSx new-AF and prior-AF subgroups (all p < 0.05) (Table 2). Conclusions Patients undergoing open-heart aortic or mitral valve surgery are at risk of significant adverse clinical outcomes including death, heart failure and ischaemic stroke, with the target valve and baseline AF status having a differential impact on clinical outcomes. Drivers behind these high rates of adverse outcomes should be explored further and strategies should be developed and tailored accordingly to different surgical patient groups to improve their prognosis.

Transcription Factor Forkhead Box Protein 3 (FOXP3) as a Prognostic Indicator for Postoperative Outcomes in Patients with Breast Cancer: Establishment of a Prognostic Nomogram.

The current investigation is to assess FOXP3 expression in breast cancer patients and evaluate the predictive significance of FOXP3. A cohort of 313 cases between January 2015 and November 2015 were enrolled this research. Immunohistochemistry (IHC) assay was utilized to detect the expression levels of FOXP3 in primary breast carcinoma specimens. These patients were separated into two groups by semiquantitative scoring approach. Chi-square test and Fisher's exact test were conducted to investigate the correlations between FOXP3 expression in tumors and clinicopathological variables. Kaplan-Meier method and Log rank test were utilized to generate survival curves for disease-free survival (DFS) and overall survival (OS). The independent factors were examined using Cox regression analysis. Nomogram models were created for assessing DFS and OS rates. Depending on the levels of FOXP3 expression in tumors, these patients were categorized into two groups: low FOXP3 expression (174 cases) and high FOXP3 expression (139 cases). The patients exhibiting low levels of FOXP3 expression in tumors demonstrated a longer survival duration contrasted with those with high expression (DFS: 88.75 vs 65.87 months, χ2=36.1100, P<0.0001; OS: 89.70 vs 78.37 months, χ2=32.4900, P<0.0001). Multivariate analysis revealed that FOXP3 was a significant prognostic factor [DFS: hazard ratio (HR): 2.822, 95% CI: 1.595-4.992, P<0.0001; OS: HR: 3.232, 95% CI: 1.812-5.763, P<0.0001]. The good predictive clinical utility of FOXP3-based nomograms within the threshold probability range for different survival rates was demonstrated by calibration curve and decision curve analyses. FOXP3 expression serves as a crucial prognostic indicator in breast cancer patients, and may aid preoperative evaluation in clinical practice.

Distant metastasis patterns among lung cancer subtypes and impact of primary tumor resection on survival in metastatic lung cancer using SEER database.

This research aimed to systematically uncover the metastatic characteristics and survival rates of lung cancer subtypes and to evaluate the impact of surgery at the primary tumor site on cancer-specific survival in DM lung cancer. We used the Surveillance, Epidemiology, and End Results (SEER) database (2010-2019) to identify primary lung cancers with DM at presentation (M1). Kaplan-Meier (KM) survival curves were generated and compared utilizing log-rank tests. Cox regression methods were employed to determine hazard ratios (HR) and 95% confidence intervals related to CSS factors. Inverse probability of treatment weighting (IPTW) was applied to reduce bias. We analyzed 77,827 M1 lung cancer cases, with 41.22% having DM at presentation. Bone metastasis was most common in ADC, ASC, SCC, LCC; brain in LCNEC; liver in SCLC. Lung was common in TC + AC and SCC. Long-term survival was best in TC + AC and worst in SCLC (p < 0.001). Male gender, age < 50, primary tumor site (main bronchus, lower lobe), large tumor diameter, ADC/SCLC/SCC pathology, and regional lymph node involvement were significant risk factors for multiorgan metastasis. Age ≥ 50, male, large tumor diameter, positive lymph nodes, and multiorgan metastases were associated with lower CSS. In contrast, radiotherapy, chemotherapy, systemic therapy, and surgery were associated with higher CSS rates. Primary tumor resection improved survival in lung cancer patients (excluding small cell lung cancer, SCLC) with single organ metastases (KM log rank p < 0.001, HR = 0.6165; 95% CI (0.5468-0.6951)), especially in brain (p < 0.001, HR = 0.6467; 95% CI (0.5505-0.7596)) and bone (p = 0.182, HR = 0.6289; p < 0.01), but not in liver or intrapulmonary metastases after IPTW. Significant differences in DM patterns and corresponding survival rates exist among lung cancer subtypes. Primary tumor resection improves survival in lung cancer patients (excluding small cell lung cancer, SCLC) with single organ metastases, with better outcomes in patients with brain and bone metastases, while no significant benefit was seen in patients with liver and intrapulmonary metastases.

Abstract P429: Stronger Association of Angiotensinogen with Mortality than Renin or Lactate in Critical Illness

Introduction: Sepsis and septic shock remain global healthcare issues associated with high mortality rates affecting millions every year despite best care efforts. Activation of the renin-angiotensin-system (RAS) is an early event in sepsis, and renin levels may more strongly associate with mortality than serum lactate, a widely accepted index of patient status. We postulated that reduced levels of Angiotensinogen (AGT) may reflect a dysfunctional RAS driven by high renin levels but an attenuated expression of Ang II to adequately support tissue perfusion and blood pressure. This study compared the association with mortality of AGT to serum lactate and active renin in a subset of the VICTAS (Vitamin C, Thiamine, and Steroids in Sepsis) cohort (N=103) at baseline (day 0) prior to treatment. Methods: Serum levels of intact AGT and active renin protein were quantified by separate ELISAs. Biomarker discrimination for all-cause 30-day mortality was compared by receiver operating characteristic (ROC) curves generated by logistic regression models adjusted for age, sex, sequential organ failure assessment (SOFA) score, systolic blood pressure, and in-hospital vasopressor support. Association of serum AGT, renin, and lactate with mortality was assessed by Kaplan-Meier curves with log rank test and hazard ratios derived from Cox regression. Results: Median [interquartile range] serum levels for AGT were: 114 [78.2-205.4] nM; renin: 4.9 [2.2-13.6] pM; and lactate: 2.6 [1.7-3.8] mM. ROC curves revealed better discrimination of AGT for mortality than either active renin or lactate. The area under the curve (AUC) of AGT (0.82, 95% CI: 0.70, 0.93) was greater than lactate (AUC=0.68, 95% CI: 0.57, 0.80; p=0.022). Kaplan-Meier curves and log rank test also revealed that AGT levels below 114 nM associated with reduced survival. Renin levels greater than 4.9 pM were also associated with patient mortality albeit less than that for AGT while higher lactate levels (&gt;2.6 mM) were not associated with mortality in this cohort. Conclusion: AGT levels more strongly associated with 30-day mortality than renin or lactate in the VICTAS cohort. Reduced AGT may reflect increased consumption by high renin coupled with reduced expression by the liver ultimately impairing Ang II-AT 1 R tone in critically ill patients. The prospective assessment of circulating AGT may facilitate more precise therapeutic approaches treatment to restore a dysfunctional RAS and improve overall mortality in sepsis.

Recurrent thrombosis and patency of the arteriovenous access in patients receiving hemodialysis.

Thrombosis of the vascular access in patients with end-stage renal disease requiring hemodialysis are common and require timely interventional procedures to restore patency. The aim of the current study was to identify factors having a significant effect on patency rates after access thrombosis. Our hypothesis was the length of time between the initial clotting of the access and the subsequent percutaneous declotting impacts the patency rates of the vascular access. In this retrospective cohort study, patients with a clotted arteriovenous access between Jan 1, 2011, and Jan 1, 2016, were included. Demographics, access history, and associated details of the access procedure were reviewed from the electronic medical record. Statistical analysis was done using t-test and chi-square or fisher exact tests to compare arteriovenous fistulae (AVF) and arteriovenous grafts (AVG). Primary patency, defined as the time from index procedure to endpoint, was analyzed using the Kaplan-Meier method and log rank test. There were 883 percutaneous declotting procedures reviewed. About 351 procedures were performed in patients with an AVF and 532 with an AVG. The mean time from thrombosis to declotting was 1.71 ± 2.29 days. The overall median primary patency for both AVF and AVG was 43 days with no difference in patency between patients with AVF (39 days) versus AVG (42 days; p = 0.385). The time period from access thrombosis to declotting did not affect patency rates for either AVG or AVF (p = 0.385). On multivariable analysis, prior intervention (HR: 1.32, 95% CI: 1.14-1.53, p < 0.001) and cardiovascular disease (HR: 1.19, 95% CI: 1.03-1.37, p = 0.016) were independently associated with access patency. Time from thrombosis to declotting did not affect patency rates however once there was a thrombotic event, recurrent thrombosis requiring intervention was common with patency significantly decreased. Future prospective studies to validate our results and study pathogenic mechanisms of recurrent thrombosis are warranted.

Patients With Dysplasia Achieve Similar Outcomes and Survivorship to Nondysplastic Patients 10 Years After Hip Arthroscopy for Femoroacetabular Impingement

To determine the long-term outcomes of hip arthroscopy (HA) for femoroacetabular impingement (FAI) in the presence of concomitant lateral rim dysplasia compared with a matched control group. Patients undergoing HA between January 2009 and October 2013 with minimum 10-year follow-up were reviewed. The inclusion criteria consisted of patients undergoing HA for FAI with evidence of lateral rim dysplasia (lateral-center edge angle [LCEA] < 25°). Patients with lateral rim dysplasia were matched to patients with an LCEA greater than 30° based on sex, Tönnis grade, and age. Outcomes included survival (avoidance of total hip replacement [THR]), repeated HA, and patient-reported outcomes (PROs). Survivorship was assessed using a Kaplan-Meier curve and log rank test, whereas revision rates between groups were assessed using χ2 analysis. Between- and within-group analyses of PROs were conducted using the Mann-Whitney U test and Wilcoxon signed rank test, respectively. The proportion of cases achieving the patient acceptable symptom state was compared between groups using χ2 analysis. This study comprised 46 dysplasia cases and 90 control cases. There was no statistically significant difference between groups in baseline metrics apart from the LCEA (P < .001), Sharp angle (P < .001), and Tönnis angle (P < .001). By 10 years postoperatively, 9% of dysplasia cases and 4% of control cases underwent conversion to THR. There was no statistically significant difference between groups in survival or revision rates. Both groups reported improvements in PROs, and there was no difference between PRO scores at either time point. Excluding cases that underwent THR, 84% and 83% of dysplasia and control cases, respectively, achieved the patient acceptable symptom state. HA for symptomatic FAI is a successful treatment in cases in which dysplasia is present. Low complication rates, comparable outcomes to cases without lateral rim dysplasia, and a high survivorship rate of 91% at minimum 10-year follow-up are observed. Increasing Tönnis angle preoperatively may increase the risk of THR conversion. Level IV, retrospective cohort study.

Prognostic Role of Pre-Treatment Body Composition Parameters in Patients Undergoing First-Line Immunotherapy for Metastatic Renal Cell Carcinoma.

We investigated the relationship between body mass index (BMI), radiological body composition, and survival outcomes in patients with metastatic renal cell carcinoma (mRCC) underwent first-line immune checkpoint inhibitor (ICI)-based therapy. Analyzing data from 102 patients treated between November 2019 and March 2023, pre-treatment computed tomography (CT) scans assessed fat and muscle areas. BMI and body composition indices were examined, including skeletal muscle index, subcutaneous fat index (SFI), visceral fat index, and total fat index. Kaplan-Meier curves and Log rank tests compared progression-free survival (PFS) and overall survival (OS), while multivariable Cox proportional regression analysis was performed to identify the variables significantly associated with survival outcomes. 54 patients (52.9%) experienced disease progression, and 26 (25.5%) died during a median follow-up of 17.4 months. High SFI was significantly associated with improved OS (p = 0.018) but not PFS (p = 0.090). Multivariable analysis confirmed the positive impact of high SFI on OS (adjusted HR: 0.37, p = 0.029) and suggested a trend towards improved PFS (adjusted HR: 0.61, p = 0.088). Notably, in the ipilimumab + nivolumab subgroup, high SFI significantly correlated with both PFS and OS (p = 0.047 and p = 0.012, respectively). High SFI predicts favorable OS in patients with mRCC receiving first-line ICI-based therapy, especially patients treated with ipilimumab + nivolumab displayed a significant association between high SFI and favorable PFS and OS.

Is laparoscopic approach as treatment of large gastric GIST acceptable?

Laparoscopic surgery is widely used for small gastric gastrointestinal stromal tumors (GISTs) (≤ 5cm) but remains a controversial approach for larger gastric GISTs (> 5cm). This study aims to compare short- and long-term outcomes of laparoscopic resection in comparison with open resection for gastric GISTs measuring over 5cm. All patients receiving surgery for gastric GIST > 5cm between 2000 and 2021 in a single tertiary hospital were included. Data were collected from prospectively maintained records. Kaplan-Meier method and log rank test were used to compare survival outcomes. Among 108 included patients, 59 patients had minimally invasive (MI) surgery (54.6%) whereas 49 patients had open surgery (46.4%). The rate of overall postoperative morbidity was 14.8% and the median length was significantly shorter in the MI group [4 (range 2-30) vs. 7 (range 4-33) days; P = 0.007]. The overall R0 resection rate was 98.2% and the rate of tumor rupture was 13%, not different between the two groups. Recurrence occurred in 24% of the whole population without any difference between groups (20.3% vs. 28.7%, p = 0.31). Minimally invasive surgery was not found as a negative prognostic disease-free survival factor. Laparoscopic surgery could be a safe and feasible alternative to open surgery in large gastric GIST, bringing the benefits of minimally invasive surgery without compromising oncologic results.

Clinicopathological analysis of gastric adenocarcinoma with elevated serum alpha-fetoprotein and enteroblastic differentiation

Objective: To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED). Methods: The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis. Results: Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177-GNAS, AIM1-FGFR3, and EPHA6-ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis (P＜0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone (P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone (P＜0.05). Conclusions: Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.

Surgery Prolongs Five-Year Survival for Nonmetastatic Colon Neuroendocrine Tumors

Abstract Background: While treatment guidelines for colon neuroendocrine tumors recommend surgical intervention when feasible, evidence in the literature is limited for patients with nonmetastatic tumors. Objectives: This study assessed the efficacy of surgery in terms of five year survival for patients with nonmetastatic colon neuroendocrine tumors. Design: This was a retrospective cohort study. Patient and Methods: This study used the National Cancer Database (NCDB) which compiles data from 1500 + facilities accredited to the Commission on Cancer. Data from patients with histologically confirmed colon neuroendocrine tumors from 2007 to 2018 were collected. Other inclusion criteria were age more than 18 years, nonmetastatic, nonpalliative care, known surgery status/type, and chemotherapy status. The five year survival rates were assessed using Kaplan–Meier curves and multivariate adjusted Cox proportional hazards regression to analyze the efficacy of surgery for these tumors. In addition, sensitivity analyses were performed to determine the associations in patients with well differentiated and early stage (stage 1) tumors. Main Outcome Measure: The main outcome was five year overall survival. Sample Size: A total of 3,340 patients met the inclusion criteria from the NCDB. Results: The majority of patients received some form of surgery (95.8%), while fewer patients (4.3%) received nonsurgical treatment. Overall, patients were on average 61.5 ± 13.3 years old, female (54.3%), and majority white (77.7%). Five year survival rates were 65.5% for the no surgery group and 79.5% for the surgery group [Kaplan–Meier log rank, P &lt; .0001]. Moreover, multivariate proportional hazards regression showed prolonged five year survival after surgery [adjusted hazards ratio (aHR) (95% confidence interval): 0.39 (0.28–0.54)]. In addition, all sensitivity analyses revealed prolonged survival of patients who underwent surgery. Conclusion: To our knowledge, this is the first study to assess survival for nonmetastatic colon neuroendocrine tumors using a national database. Limitations: This study was limited by retrospective review, potential selection bias from a registry, and missing data. Conflicts of Interest: None.

Effect of Preoperative Serum Lactate Dehydrogenase-to-Albumin Ratio on the Survival of Oral Cancer: A Retrospective Study.

Several studies have investigated the relationship between serum lactate dehydrogenase-to-albumin ratio (LAR) and the prognosis of cancers. However, no studies have explored the association between serum LAR and the survival of oral cancer (OC). This study was aimed to determine the association of serum LAR with the overall survival (OS) of OC. One hundred and ninety patients with OC were included in this study between January 2018 and December 2019. Log rank test and Kaplan-Meier method were used to compare the survival rate of OC between the low LAR group and the high LAR group. The association between serum LAR and the survival of OC patients was determined via univariate and multivariate Cox regression analyses. Kaplan-Meier analysis and Log rank test indicated that the OS rate in low LAR group was significantly higher than that in high LAR group (P < 0.05). Univariate cox analysis showed that TNM III-IV stage, serum LDH > 162 U/L, and serum LAR > 3.79 were significantly associated with the OS of OC patients. Multivariate Cox analysis suggested that the TNM III-IV stage (HR, 2.317; 95% CI, 1.423-3.774, P = 0.001) and serum LAR > 3.79 (HR, 5.138; 95% CI, 2.245-11.756, P = 0.000) were independently related with poor OS of OC patients. High serum LAR (>3.79) is an independent predictor of adverse prognosis in OC patients. LAR could be used as a promising marker for predicting the OS of OC patients.

Nutritional Indices Predict All Cause Mortality in Patients with Multi-/Rifampicin-Drug Resistant Tuberculosis.

Multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) with high mortality remains a public health crisis and health security threat. This study aimed to explore the predictive value of nutritional indices for all-cause mortality (ACM) in MDR/RR-TB patients. We retrospectively recruited MDR/RR-TB patients between January 2015 and December 2021, randomly assigning them to training and validation cohorts. Patients were divided into high nutritional risk groups (HNRGs) and low nutritional risk groups (LNRGs) based on the optimal cut-off value obtained from receiver operating characteristic (ROC) analyses of the hemoglobin-albumin-lymphocyte-platelet (HALP) score, prognostic nutritional index (PNI), and controlling nutritional status (CONUT) score. In the training cohort, Kaplan-Meier survival curves and Log rank tests were used to compare overall survival (OS) between the groups. Cox risk proportion regression analyses were used to explore the risk factors of ACM in patients with MDR/RR-TB. The predictive performance of ACM was assessed using area under the curve (AUC), sensitivity and specificity of ROC analyses. A total of 524 MDR/RR-TB patients, with 255 in the training cohort and 269 in the validation cohort, were included. Survival analyses in the training cohort revealed significantly lower OS in the HNRGs compared to the LNRGs. After adjusting for covariates, multivariate analysis identified low HALP score, low PNI and high CONUT score were independent risk factors for ACM in MDR/RR-TB patients. ROC analyses demonstrated good predictive performance for ACM with AUCs of 0.765, 0.783, 0.807, and 0.811 for HALP score, PNI, CONUT score, and their combination, respectively. Similar results were observed in the validation set. HALP score, PNI, and CONUT scores could effectively predict ACM in patients with MDR/RR-TB. Hence, routine screening for malnutrition should be given more attention in clinical practice to identify MDR/RR-TB patients at higher risk of mortality and provide them with nutritional support to reduce mortality.

Survival analysis of adult visceral leishmaniasis patients admitted to Metema Hospital, Metema, Ethiopia: a hospital-based cross-sectional study.

Visceral leishmaniasis (VL) is a neglected tropical disease that mostly affects the working class and impoverished segments of society, having a significant negative effect on the economic development of the affected nation. While anti-leishmanial medications lower mortality among VL patients, patients may still die or require more time to recover while receiving treatment. In this regard, there are limited studies in Ethiopia. This study aims to determine the time to recovery and its associated predictors among adult VL patients at Metema Hospital, Metema, Ethiopia. A hospital-based cross-sectional study was employed and the data were collected from patient's charts from September 2017 to September 2021. Data were entered and analysed using EpiData version 3.1, Stata version 14.2 and R version 3.4.0 statistical software. Kaplan-Meier survival curves and logrank tests were used to compare the survival time. The Cox proportional hazards model assumption and model fitness were checked and used to identify statistical association predictors in VL patients. The Cox proportional hazards model was fitted. The overall medium recovery time was 7d (minimum 4, maximum 14). The variables of nasal bleeding (adjusted hazard ratio [aHR] 0.44 [95% confidence interval {CI} 0.19 to 0.89]), no comorbidity (aHR 2.29 [95% CI 1.27 to 4.11]), relapse of VL (aHR 0.33 [95% CI 0.15 to 0.75]), low parasite load (aHR 2.58 [95% CI 1.48 to 4.51]) and ambulatory (aHR 3.26 [95% CI 2.45 to 6.53]) were significantly associated with time to recovery in VL patients. Patients with comorbidities, nasal bleeding, relapse of VL, bedridden and high parasite load should be treated and monitored carefully to recover quickly from their illness.

Biologic and prognostic significance of HER2-low and ER-low expressions in de novo metastatic breast cancer.

e13170 Background: It is unclear whether ER-low-positive (ER-low) and HER2-low-positive (HER2-low) biomarkers, as new biological subtypes, have different biological and clinicopathological characteristics in de novo metastatic breast cancer (dnMBC). Per ASCO/CAP guidelines, tumors were defined as HER2-low-positive (HER2-low) if they had an HER2 immunohistochemical (IHC) score of 1+ or 2+ with negative in situ hybridization assay and HER2-0 if they had an HER2 IHC score of 0; ER-low refers to the tumor IHC staining of 1%-10%, if the staining is less than 1%, it is defined as ER-0. This study aimed to investigate whether ER-low and HER2-low expressions is associated with clinicopathologic characteristics and prognosis among patients with de novo metastatic breast cancer. The study was approved by the Ethics Committee of Hebei Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine (2017-AF29-058). Methods: Using hospital-based database, we identified patients with dnMBC diagnosed between 2010 and 2017, retrospectively collecting demographic data, tumor characteristics, treatment types, histopathological report and survival data. According to ASCO/CAP guideline recommendations, patient-specific histopathological results were classified, and IHC-based breast cancer markers, mainly including ER-low and HER2-low, were evaluated and analyzed. Median survival time (MST) was estimated by Kaplan-Meier method and log rank test. Univariable and multivariable analyses were performed using the Cox proportional hazard model to identify statistically significant prognostic factors. All statistical analyses were performed using Stata 18.0. Results: A total of 518 patients (median age of 53 years) were included in this study, including 194 patients with HER2-low, 201 patients with HER2-low, 36 patients with ER-low, and 179 patients with ER-0. Expression of HER2-low was significantly more common among ER-positive tumors (excluding the ER-low) compared with HER2-0 tumors (71.1% vs. 62.2%; P &lt; .001). The MST in the HER2-low cohort was longer than that in the HER2-0 cohort (40 vs. 30 months; HR,0.65; 95% CI, 0.52-0.82, p=.0001); while the MST of ER-low cohort was slightly longer than that of the ER-0 cohort (27 vs. 20 months; HR,0.75; 95% CI, 0.51-1.11, p=.231), but there was no statistical difference. Notably, in the metastasis pattern cohort, HER2-low showed a significantly higher MST compared with HER2-0 (P&lt;.001), with a MST of up to 68 months for bone-only metastases. There was no significant difference in MST between ER-low and ER-0 regardless of whether patients received endocrine therapy (P=.135). Conclusions: In the present study, for dnMBC patients, ER-low expression has similar biological and clinical outcome characteristics as ER-0. However, unlike HER2-0, HER2-low expression may predict a survival benefit in bone-only metastases.

Impact of rituximab maintenance on survival of patients with mantle cell lymphoma: A north Indian tertiary care center experience.

e19047 Background: Mantle cell lymphoma (MCL) is an aggressive variant of non-Hodgkin lymphoma. Indian data is scarce owing to its rarity in south-east Asia. Till now, studies have not shown overall survival benefit with rituximab maintenance (RM). Our study aims to assess if RM improves overall survival of MCL patients. Methods: We retrospectively analysed clinicopathological data of 90 transplant-ineligible MCL patients treated between January’2013-December’2023 at Institute Rotary Cancer Hospital - All India Institute of Medical Sciences, New Delhi, India. Rituximab-based induction chemotherapy was used in all patients as per institutional protocol. RM was used in twenty-eight (31.0%) patients due to financial constraints. Primary outcome was overall survival (OS). Secondary outcomes were event free survival (EFS) and factors affecting OS, EFS. OS was defined as time from treatment initiation to demise from any cause or last follow-up. EFS was defined as time from treatment initiation to disease progression or relapse or demise from any cause. Response was assessed by modified Cheson’s lymphoma response evaluation criteria. STATA 13.0 was used to assess survival by Kaplan-Meier analysis and log rank test. Factors affecting survival were assessed by multivariate analysis (Cox proportional hazards model) and expressed as adjusted hazard ratio (aHR). p value &lt; 0.05 defined statistical significance. Results: Median age was sixty years; male-female ratio 3:1. Thirty-five (39.0%) had one or more co-morbidities, 79(88.0%) generalised lymphadenopathy, 72(80.0%) extra-nodal involvement, 49(54.0%) B symptoms, 84(93.0%) advanced stage (III/IV), 49(54.0%) high risk MCL international prognostic index (MIPI). Clinical and tumor characteristics, response rates after initial induction were similar in both maintenance and non-maintenance groups. Overall, 52(58.0%) patients were alive with median follow-up of 63.0 months (inter-quartile range 37.0-90.0 months). Median OS was 37.5 months in non-maintenance group and did not reach in maintenance group. Estimated 1.0-, 2.0, 3.0-year OS were 100.0%, 91.0%, 81.0% vs 75.0%, 63.0%, 55.0% respectively in maintenance vs non-maintenance group. RM was significantly associated with better OS [aHR (95% confidence interval): 0.31 (0.13-0.75), p=0.01]. Advanced stage, Eastern Co-operative Oncology Group performance status (ECOG PS) ≥2 at presentation were also significant factors for poor OS. Median EFS was significantly lower in non-maintenance group [14.0 vs 42.5 months; aHR (95% confidence interval): 0.34 (0.18-0.64), p=0.001]. Advanced stage, anemia, high risk MIPI at presentation were also significant factors for poor EFS. Conclusions: This was the first study from south-east Asia demonstrating impact of rituximab maintenance in MCL. Rituximab maintenance significantly improved OS and EFS of MCL patients.

Racial differences in genomic profiles and clinical outcomes of patients with colorectal carcinoma: A single institution retrospective study.

e15582 Background: In the era of precision oncology, there is an immediate need to study the heterogeneity of molecular biology and clinical outcomes in racially diverse colorectal cancer (CRC) patients. Black patients are known to have poorer outcomes compared to their white counterparts. Understanding differences in patients’ molecular and genomic profiles may help explain these racial disparities. Methods: Demographic and clinical outcome data was abstracted from medical records of colorectal cancer patients who were diagnosed between 2008 and 2021 at The University of South Alabama. Tumor only next generation sequencing (NGS) of DNA (592 or WES) and RNA (WTS) was performed at Caris Life Sciences (Phoenix, AZ). Overall survival (OS) was defined as time from diagnosis to death or last contact. Descriptive analyses were performed using t-test and chi-square test, survival analyses were performed using Kaplan-Meier method and Log rank test (GraphPad Prism version 10.1.1). Results: 66 patients with CRC were included, 73% were white and 27% were black. The median age for white patients was 60.5 years and for black patients was 55.5 years (p = 0.049). In the white population, 52.1% of the patients were male and 47.9% were female. In the black population, 33.3% were male and 66.7% were female. The most common sites of malignancy for white patients were rectum (32.6%) and sigmoid (26.1%), whereas for black patients the most common sites were sigmoid (27.8%) and cecum (22.2%). Overall, the most common mutations were TP53 (68.2%), APC (65.2%), KRAS (47%), SMAD4 (16.7%), and FBXW7 (13.6%). The prevalence rates of TP53 (77.8 vs 64.6%), APC (72.2 vs 62.5%), KRAS (66.7 vs 39.6%), and SMAD4 (27.8 vs 14.6%) trended higher in black patients, with KRAS being statistically significant (p = 0.049). FBXW7 trended higher in white patients (14.6 vs 11.1%). Eleven (23%) white patients had a variant of uncertain significance in the ATM gene, which was not observed in black patients. More white patients had stage IV disease compared to black patients (69% vs 50%). No statistically significant difference in OS was found between races (HR 0.68, 95% CI of 0.35 to 1.3, p = 0.2). However, white patients had a median OS of 1334 days compared to 927 days for black patients. Conclusions: White and black CRC patients have unique molecular tumor profiles that may better explain the differences in survival. Our results warrant larger studies with racially and ethnically diverse patient populations to explore these racial disparities and close the gap in colorectal cancer care.

Survival after Stereotactic Radiosurgery in the Era of Targeted Therapy: Number of Metastases No Longer Matters.

Randomised control trial data support the use of stereotactic radiosurgery (SRS) in up to 4 brain metastases (BMs), with non-randomised prospective data complementing this for up to 10 BMs. There is debate in the neuro-oncology community as to the appropriateness of SRS in patients with >10 BMs. We present data from a large single-centre cohort, reporting survival in those with >10 BMs and in a >20 BMs subgroup. A total of 1181 patients receiving SRS for BMs were included. Data were collected prospectively from the time of SRS referral. Kaplan-Meier graphs and logrank tests were used to compare survival between groups. Multivariate analysis was performed using the Cox proportional hazards model to account for differences in group characteristics. Median survival with 1 BM (n = 379), 2-4 BMs (n = 438), 5-10 BMs (n = 236), and >10 BMs (n = 128) was 12.49, 10.22, 10.68, and 10.09 months, respectively. Using 2-4 BMs as the reference group, survival was not significantly different in those with >10 BMs in either our univariable (p = 0.6882) or multivariable analysis (p = 0.0564). In our subgroup analyses, median survival for those with >20 BMs was comparable to those with 2-4 BMs (10.09 vs. 10.22 months, p = 0.3558). This study contributes a large dataset to the existing literature on SRS for those with multi-metastases and supports growing evidence that those with >10 BMs should be considered for SRS.

Mesenchymal-epithelial transition factor amplification correlates with adverse pathological features and poor clinical outcome in colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer-related mortality worldwide. Mesenchymal-epithelial transition factor (MET) gene participates in multiple tumor biology and shows clinical potential for pharmacological manipulation in tumor treatment. MET amplification has been reported in CRC, but data are very limited. Investigating pathological values of MET in CRC may provide new therapeutic and genetic screening options in future clinical practice. To determine the pathological significance of MET amplification in CRC and to propose a feasible screening strategy. A number of 205 newly diagnosed CRC patients undergoing surgical resection without any preoperative therapy at Shenzhen Cancer Hospital of Chinese Academy of Medical Sciences were recruited. All patients were without RAS/RAF mutation or microsatellite instability-high. MET amplification and c-MET protein expression were analyzed using fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), respectively. Correlations between MET aberration and pathological features were detected using the chi-squared test. Progression free survival (PFS) during the two-year follow-up was detected using the Kaplan-Meier method and log rank test. The results of MET FISH and IHC were compared using one-way ANOVA. Polysomy-induced MET amplification was observed in 14.4% of cases, and focal MET amplification was not detected. Polysomy-induced MET amplification was associated with a higher frequency of lymph node metastasis (LNM) (P < 0.001) and higher tumor budding grade (P = 0.02). In the survival analysis, significant difference was detected between patients with amplified- and non-amplified MET in a two-year follow-up after the first diagnosis (P = 0.001). C-MET scores of 0, 1+, 2+, and 3+ were observed in 1.4%, 24.9%, 54.7%, and 19.0% of tumors, respectively. C-MET overexpression correlated with higher frequency of LNM (P = 0.002), but no significant difference of PFS was detected between patients with different protein levels. In terms of concordance between MET FISH and IHC results, MET copy number showed no difference in c-MET IHC 0/1+ (3.35 ± 0.18), 2+ (3.29 ± 0.11) and 3+ (3.58 ± 0.22) cohorts, and the MET-to-CEP7 ratio showed no difference in three groups (1.09 ± 0.02, 1.10 ± 0.01, and 1.09 ± 0.03). In CRC, focal MET amplification was a rare event. Polysomy-induced MET amplification correlated with adverse pathological characteristics and poor prognosis. IHC was a poor screening tool for MET amplification.

#2251 Long-term systolic blood pressure variability as an independent risk factor for cardiovascular events in kidney transplant recipients

Abstract Background and Aims Cardiovascular (CV) events represent the main cause of death in patients undergoing renal transplantation. Several studies have described the role of blood pressure variability (BPV) in predicting all-cause mortality and fatal and non-fatal CV events in the general population and in diabetic patients. Systolic blood pressure variability (SBPV) has recently been proposed as a predictor of clinical outcomes in patients with chronic kidney disease. However, evidence is still scarce about the prognostic role of BPV in the setting of renal transplantation. The aim of the study was to evaluate the role of long-term SBPV in the development of fatal and non-fatal CV events (myocardial infarction, unstable angina or revascularization, stroke and hospitalization for heart failure) in subjects undergoing kidney transplantation. Method We performed a single-center retrospective observational analysis in a cohort of 272 kidney transplant patients (mean age 64 ± 13 years, 66% men), with a transplant duration ≥12 months and with at least 6 blood pressure measurements at defined intervals (3 months ±15 days) over an assessment period of 18 months. BPV was expressed as standard deviation of ambulatory systolic blood pressure (SBP) and patients were accordingly classified in tertiles (low &amp;lt;9.3 mmHg, medium 9.3-13 mmHg, high &amp;gt;13 mmHg). The role of SBPV was analyzed by Kaplan-Meier (logrank) and its independent effect by Cox Regression. Results Over a mean follow-up of 58.7 ± 17.2 months, 27 subjects (9.9%) developed CV events. For each increase of 2.7 mmHg in SBP standard deviation, the risk for fatal or non-fatal CV events increased almost 3-folds (P = 0.02) and patients in the highest tertile of SBP standard deviation showed a 4-fold increased risk (P = 0.01) (Fig. 1). This relationship was maintained even after incremental adjustment for time-averaged pulse pressure, age, diabetes, prior CV event, and dialysis vintage (HR 3.2, 95% CI 1.1–10.0, p 0.04) (Table 1). Conclusion Long-term BPV represents an independent risk factor for CV events in kidney transplant patients. It is therefore essential to seek for stable long-term blood pressure levels in this population in order to minimize the residual CV risk.

Abstract PO2-15-09: Immune related cell fraction in peripheral blood and outcomes of advanced breast cancer patients treated with Eribulin

Abstract Background: Eribulin prolongs overall survival (OS) of patients with advanced breast cancer, and an ad-hoc analysis of the EMBRACE trial showed that baseline absolute lymphocyte count (ALC) was a predictor of OS prolongation. It has been suggested that eribulin improves the immune response to the tumor by improving the hypoxic environment through remodeling of local tumor vessels and reducing hypoxic stress, leading to OS prolongation. However, the details of the immune response mediated by eribulin remain to be fully elucidated. CD8+ cells attack cancer cells as cytotoxic T cells, while regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) suppress activated T cells that attack cancer cells. In this study, we focused on CD8+ cytotoxic T cells, Tregs, MDSCs, and CD4-CD25-FoxP3+ cells in peripheral blood, analyzed the changes of those immune cells before and after eribulin treatment, and examined the effects on the outcomes of breast cancer patients. Methods: Nineteen patients with advanced or recurrent breast cancer treated with eribulin from April 2021 to May 2023 at our hospital were included. Peripheral blood was collected before drug administration as the first treatment (pre-treatment) and before drug administration in the second course (post-treatment), and the cell fractions, including CD4+ cells, CD8+ cells, CD4+CD25+FoxP3+ Tregs, CD11b+CD14+CD33+ MDSCs, and CD4-CD25-FoxP3+ cells, were analyzed by flow cytometry. The cutoff value for ALC was set at 1000 and NLR at 3.0, and each cell fraction was set to its respective median. Kaplan-Meier plots and logrank tests for progression-free survival (PFS) or OS were applied. Results: CD4+ cells were significantly lower post-treatment compared to pre-treatment (p=0.0140). Further, Tregs were significantly lower post-treatment compared to pre-treatment (p=0.0258). There were no significant changes in the levels of CD8+ cells, MDSCs, and CD4-CD25-FoxP3+ cells between pre- and post-treatment. We examined the association between each cell fraction and ALC or NLR, and found that CD4-CD25-FoxP3+ cells were significantly higher in cases with high NLR (p=0.0110). Analysis of the association between each cell fraction and prognosis at pre-treatment revealed that the high CD8+ cell group had significantly better PFS and OS than the low CD8+ cell group (p=0.0129 and p=0.0077, respectively). Interestingly, the high CD4-CD25-FoxP3+ cell group had significantly worse PFS than the low CD4-CD25-FoxP3+ cell group (p=0.0026). Conclusion: In the current study, Tregs in the peripheral blood of breast cancer patients significantly decreased after eribulin treatment, suggesting that eribulin may improve the immune microenvironment by suppressing immunosuppressive cells in cancer, including Tregs. In addition, the CD4-CD25-FoxP3+ cell fraction may serve as a biomarker for eribulin therapy, and further studies are needed to elucidate the details, including analysis of the constituent cells within the fraction. Citation Format: Masayuki Nagahashi, Ayako Bun, Mamiko Kuroiwa, Miki Komatsu, Sayaka Urano, Yukie Fujimoto, Aoi Oshiro, Ayumu Mitsuyoshi, Haruka Kanaoka, Akira Hattori, Reiko Fukui, Tomoko Higuchi, Arisa Nishimukai, Keiko Murase, Yuichi Takatsuka, Yasuo Miyoshi. Immune related cell fraction in peripheral blood and outcomes of advanced breast cancer patients treated with Eribulin [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-15-09.