Survival Curves Of Patients Research Articles

Preoperative CT-based morphological heterogeneity for predicting survival in patients with colorectal cancer liver metastases after surgical resection: a retrospective study

ObjectiveTo explore the value of preoperative CT-based morphological heterogeneity (MH) for predicting local tumor disease-free survival (LTDFS) and progression-free survival (PFS) in patients with colorectal cancer liver metastases (CRLM).MethodsThe latest CT data of 102 CRLM patients were retrospectively analyzed. The morphological score of each liver metastasis was obtained, and the morphological heterogeneity difference (MHD) was calculated. The receiver operating characteristic (ROC) curve was drawn, and the cutoff value was found. The Kaplan-Meier method was used to draw survival curves of patients with or without MH. The Cox regression analysis was used to build the model with MH and clinical characteristics for predicting PFS.ResultsIn 78 patients without MH, median PFS was 9.0 months (95% CI:6.5–11.5), while in 24 patients with MH, median PFS was 6.0 months (95% CI:4.0-8.1), indicating that MH significantly affected PFS (p = 0.001). MH affected PFS in both the chemotherapy group and the chemotherapy combined with targeted therapy group (p = 0.005, p = 0.043). MH, preoperative carcinoembryonic antigen (CEA) and chemotherapy after surgery were independent predictors for postoperative PFS in patients with CRLM.ConclusionPreoperative CT-based MH had good efficacy for predicting LTDFS and PFS of CRLM patients after surgical resection, regardless of preoperative treatment. MH is one of the independent predictors of PFS.

Prognostic and predictive factors in patients with metastatic gastric cancer treated with immune checkpoint inhibitors

Introduction. Microsatellite instability, PD-L1 CPS expression, high tumor mutational burden (TMB), and the presence of Epstein-Barr virus are the main tumor predictors of the response to immunotherapy in patients with metastatic gastric cancer (mGC). However, selecting patients for immunotherapy in mGC seems challenging due the lack of an optimal cut-off for PD-L1 CPS expression in microsatellite-stable gastric adenocarcinomas, significant benefit from anti-PD-L1 inhibitors in late-line treatment, and inaccessibility of Epstein-Barr virus and TMB determination in real clinical practice.Aim. The aim of our study is to determine prognostic and predictive biomarkers of patients, who received ICIs for mGC.Materials and methods. Our study included patients with mGC treated with anti-PD1 antibodies between 2018 and 2023 in five oncology centers in Moscow. Variables with p <0.05 obtained from a univariate analysis, were selected to perform multivariate analysis. According to the number of prognostic factors, patients were stratified into two groups with favorable and unfavorable prognosis. The optimal cut-off of the neutrophil-lymphocyte ratio (NLR) to predict of the efficacy of immunotherapy was determined using ROC analysis. The Kaplan–Meier method was performed to analyze survival curves of patients according to prognostic groups and NLR levels and the log-rank-test was used to compare the differences. Statistics was performed using the IBM SPSS v. 22 and PRISM 10.Results. Between January 1, 2018 and February 28, 2023, 122 patients with mGC who received ICIs were included. NLR was analyzed in 71 (58 %) patients out of 122. The median NLR was 2.36 (0.41–10.00). The cut-off of NLR for predicting mortality was 1.8 (AUC 0.81, p <0.001). The median of PFS and OS in patients with high NLR (NLR ≥1.8) were 2 and 4 months, respectively; mOS and mPFS in the low NLR group were not achieved (p <0.001). Eight factors were statistically significant in univariate analysis of patients with MSS: ECOG status (0–1 and 2–3), signet-ring cell histology, primary tumor, the number of organs with metastases (1–2 and 3 or more), ascites, pain, the line of immunotherapy (I–II and III–IV) and N LR level. Multivariate analyses revealed the presence of ascites (p = 0.001), immunotherapy administration in III– IV lines (p = 0.02), and NLR≥1.8 (p = 0.004) were independent prognostic factors for OS. Each factor was assigned with a score from 1 to 2, depending on its significance: presence of ascites – 2 points, high NLR – 2 points, III–IV line of immunotherapy – 1 point. Patients were stratified into two prognostic groups according to the number of prognostic factors – the group with favorable prognosis (0–2 points, n = 20) and unfavorable prognosis (3–5 points, n = 22). The mOS of patients with favorable and unfavorable prognosis was 6 months and 3 months, respectively (p = 0.048).Conclusion. Ascites, NLR level of ≥1.8 and administration of ICIs in late setting are associated with low efficacy of immunotherapy in patients with MSS mGC. Further research should be planned including more patients and those who did not receive ICIs to determine the prognostic significance of our model.

Study on survival analysis and influencing factors of pneumoconiosis patients in Guangzhou

Objective: To analyze the survival of pneumoconiosis patients in Guangzhou from 1958 to 2018, explore the factors affecting the survival of pneumoconiosis, and provide scientific basis for formulating the guidelines and policies for treatment and assistance of pneumoconiosis. Methods: From July 2019 to January 2020, 1194 cases of occupational pneumoconiosis patients diagnosed by institutions qualified for pneumoconiosis diagnosis in Guangzhou from June 1, 1958 to December 31, 2018 were studied. Excluding 258 patients who lacked survival data, 936 patients were included in the pneumoconiosis survival analysis. Life table method was used to estimate the survival rate, Kaplan-Meier method was used to draw the survival curve, log-rank test was used to compare the groups, and Cox proportional risk regression model was used to analyze the influencing factors of survival. Results: The 10, 20 and 30 years cumulative survival rates of pneumoconiosis patients in Guangzhou were 62.8%, 35.2% and 15.4%, respectively. The median survival time was 19.4 years. log-rank test showed that there were statistically significant differences in the survival curves of pneumoconiosis patients between group without tuberculosis and group with tuberculosis (P<0.001), and there were statistically significant differences among different stages and categories of pneumoconiosis (P<0.001). Age of exposure to dust (HR=1.03, 95%CI: 1.01-1.05), age of diagnosis (HR=1.02, 95%CI: 1.00-1.04), combined pulmonary tuberculosis (HR=1.46, 95%CI: 1.18-1.81), stage of pneumoconiosis (stage Ⅲ vs. stage Ⅰ, HR=2.26, 95%CI: 1.47-3.48) and categories of pneumoconiosis (fibrogenic mineral dust pneumoconiosis and metallogenic pneumoconiosis, HR=2.45, 95% CI: 1.61-3.74; non-fibrogenic mineral pneumoconiosis and metallogenic pneumoconiosis, HR=2.67, 95% CI: 1.47-4.87; mixed pneumoconiosis and metallogenic pneumoconiosis, HR=2.25, 95%CI: 1.11-4.56) were the factors affecting the survival time of pneumoconiosis patients (P<0.05) . Conclusion: Pulmonary tuberculosis may increase the risk of death in patients with pneumoconiosis. Mineral dust pneumoconiosis, mixed pneumoconiosis and stage Ⅲ pneumoconiosis may also have higher risk of death.

Development of a web-based tool for estimating individualized survival curves in glioblastoma using clinical, mRNA, and tumor microenvironment features with fusion techniques.

Glioblastoma (GBM), one of the most common brain tumors, is known for its low survival rates and poor treatment responses. This study aims to create a robust predictive model that integrates multiple feature types, including clinical data, RNA expression, and tumor microenvironment data, using fusion techniques to enhance model performance. We obtained data from the SEER database to assess the impact of nine demographic and clinical features on the survival of 58,495 GBM patients and built predictive machine learning models. Additionally, mRNA expression data from 600 GBM patients from TCGA, CGGA, and GEO were analyzed. We used Cox regression and LASSO to create a gene signature, which was compared against 13 published signatures for accuracy. Twenty-one machine learning models were applied to predict survival at multiple time points. Finally, we integrated multiple feature types using fusion techniques and developed a Shiny app to provide survival predictions for GBM patients. Using the SEER database, we constructed machine learning models based on nine clinical variables: age, gender, marital status, race, tumor site, laterality, surgery, chemotherapy, and radiation therapy. The best-performing model achieved AUC values of 0.775, 0.728, 0.692, and 0.683 for predicting survival at 6, 12, 18, and 24months in the testing cohort. In the merged TCGA, CGGA, and GEO cohorts, we identified 11 genes to develop predictive models. These 11 genes outperformed 13 other published gene signatures in predicting the prognosis of GBM. When incorporating mRNA features, tumor microenvironment features, and clinical variables into the fusion models, the AUC values for predicting survival at 6, 12, 18, and 24months were 0.641, 0.624, 0.655, and 0.637, respectively. A user-friendly tool for predicting the survival curve of individual GBM patients is available at https://zzubioinfo.shinyapps.io/mlGBM/ . Our study provides a web-based tool that includes two modules: one for predicting survival curves using only clinical variables, and another that integrates multiple feature types for more comprehensive predictions.

Abstract P387: Survival trajectories of the patients with malignant hypertension in the Rice Diet Program

Malignant hypertension (MH), severe arterial hypertension accompanied by retinal hemorrhage (Class III), papilledema (Class IV), or both was untreatable in 1942. Walter Kempner treated MH patients with a very low sodium (~200 mg/day), protein (~5% of calories), and fat (~5% of calories) diet with success in some patients. The scope and efficacy of this “Rice” Diet (RD) was not clear. We analyzed data from 563 non-diabetic MH patients treated from 1942-1988. The cohort, mostly male (69.4%) with a median age 51 years and median BMI 24.01 provided several interesting findings. First, the number of MH patients increased until the early 1950s, but then declined sharply by 1955, before effective pharmacotherapy was available. This sudden MH “disappearance” seems real, but is unexplained by therapy or other known events. Second, 341 MH patients showed that median survival more that doubled with RD treatment compared to untreated MH patients described by Keith-Wagner-Barker (KWB) in 1939. Third, the RD-diet survival benefit began after ~90-100 days into treatment. During the first ~90-100 RD days, survival closely tracks that of untreated MH patients described by KWB; thereafter, survival curves diverged substantially (e.g., calculated half-time survival for Class IV increased from 163.5 to 815.5 days, Figure ). Fourth, serial retinal photographs of 359 MH patients, showed that of 343 with initial hemorrhage, 36 of 177 patients surviving at 1 year (20%) still had hemorrhage; of 146 with initial papilledema, only 1 of 76 patients surviving at 1 year (1%) still had papilledema. Fifth, survival curves of MH patients with only hemorrhage or only papilledema were similar; however, survival was markedly shorter in those with both hemorrhage and papilledema, implying that the deleterious effects of vascular and neuropathic changes are independent of one another and additive. Remaining questions concern: why did MH “suddenly” disappear; how does RD impact vaculopathy; what factors impact survival trajectories.

Prognostic Factors That Affect Mortality Patients with Acinetobacter baumannii Bloodstream Infection.

To evaluate the clinical features of patients with Acinetobacter baumannii bloodstream infection (BSI). Totally 200 inpatients with Acinetobacter baumannii BSI were included, clinical features of Acinetobacter baumannii BSI inpatients between 90-day survival and 90-day mortality groups, between 30-day survival and 30-day mortality groups, between patients infected with multidrug-resistant (MDR group) and sensitive Acinetobacter baumannii (sensitive group) were analyzed. The prognostic factors of 90-day mortality were analyzed by univariate logistic regression and multivariate logistic regression. The survival curve in bloodstream infectious patients with multidrug-resistant (MDR group) and sensitive Acinetobacter baumannii (sensitive group) was analyzed by Kaplan-Meier analysis. The 90-day mortality patients had significantly higher carbapenem-resistant bacterial infection and critical care unit (ICU) admission. The 90-day and 30-day mortality groups showed higher C-reactive protein (CRP) and serum creatinine (Scr) levels and lower red blood cells (RBC) and albumin (ALB) levels than their survival counterparts, respectively. Critical surgery, ICU admission and delayed antibiotic treatment were independently prognostic risk predictors for 90-day mortality in Acinetobacter baumannii BSI patients, while critical surgery and diabetes were independently prognostic risk predictors for 90-day mortality in carbapenem-resistant Acinetobacter baumannii BSI patients. Compared with sensitive group, MDR group showed significantly longer ICU and whole hospital stay, lower levels of lymphocytes, RBC, hemoglobin, lactate dehydrogenase and ALB, higher frequency of infection originating from the skin and skin structure. Moreover, patients in the MDR group had a significantly worse overall survival than the sensitive group. We identified the prognostic factors of Acinetobacter baumannii BSI and carbapenem-resistant Acinetobacter baumannii BSI patients. Critical surgery, ICU admission, delayed antibiotic treatment or diabetes were significantly associated with the mortality of those patients. Moreover, aggressive measures to control MDR Acinetobacter baumannii could lead to improved outcomes.

Long-Term Survival in Patients With Advanced Melanoma

Long-term survival data from clinical trials show that survival curves of patients with advanced melanoma treated with immune checkpoint inhibitors (ICIs) gradually reach a plateau, suggesting that patients have a chance of achieving long-term survival. To investigate long-term survival in patients with advanced melanoma treated with ICIs outside clinical trials. Cohort study using prospectively collected data from the nationwide Dutch Melanoma Treatment Registry, including patients in the Netherlands with advanced melanoma treated with first-line ICIs from 2012 to 2019. Data were analyzed from January to September 2023. Patients were treated with first-line ipilimumab-nivolumab, antibodies that target programmed cell death (anti-PD-1), or ipilimumab. Progression-free survival (PFS) and melanoma-specific survival were analyzed, and a Cox proportional hazards model was used to investigate factors associated with PFS after reaching partial response (PR) or complete response (CR). A total of 2490 patients treated with first-line ICIs were included (median [IQR] age, 65.0 [55.3-73.0] years; 1561 male patients [62.7%]). Most patients had an Eastern Cooperative Oncology Group Performance Status of 1 or lower (2202 patients [88.5%]) and normal lactate dehydrogenase levels (1715 patients [68.9%]). PFS for all patients was 23.4% (95% CI, 21.7%-25.2%) after 3 years and 19.7% (95% CI, 18.0%-21.4%) after 5 years. Overall survival for all patients was 44.0% (95% CI, 42.1%-46.1%) after 3 years and 35.9% (95% CI, 33.9%-38.0%) after 5 years. Patients with metastases in 3 or more organ sites had a significantly higher hazard of progression after reaching PR or CR (adjusted hazard ratio, 1.37; 95% CI, 1.11-1.69). This cohort study of patients with advanced melanoma treated with ICIs in clinical practice showed that their survival reached a plateau, comparable with patients participating in clinical trials. These findings can be used in daily clinical practice to guide long-term surveillance strategies and inform both physicians and patients regarding long-term treatment outcomes.

Up-regulation of LPCAT1 is correlated with poor prognosis and promotes tumor progression in glioblastoma.

Glioblastoma (GBM) is a cancer with high malignancy because of its rapid proliferation and high metastatic ability. LPCAT1 is reported to play a tumor-promoting role in multiple cancers, but its precise molecular mechanism in GBM remains to be further explored. We aim to explore the biological role of LPCAT1 in GBM. In this study, the expression of LPCAT1 and its correlation with clinicopathological characteristics of GBM patients were analyzed based on The Cancer Genome Atlas (TCGA) dataset. Kaplan-Meier approach was adopted for plotting survival curves for patients showing different expression levels of LPCAT1. Meanwhile, LPCAT1 expression within 50 GBM tumor tissues and 30 non-tumor clinical samples was analyzed by qRT-PCR and western blot assays, respectively. Later, LPCAT1's effect on GBM tumorigenesis was analyzed in vivo and in vitro by CCK8, EdU proliferation, clone forming, scratch, TUNEL assays, and subcutaneous xenograft experiments. As a result, LPCAT1 expression elevated within GBM tumor tissues and cells. Overexpression of LPCAT1 enhanced GBM cell growth, invasion and migration, while accelerating cell cycle progression. LPCAT1 silencing significantly inhibited cell motility and proliferation in vivo and in vitro, and arrested U251 cells at G0/G1 phase. Moreover, LPCAT1 might play a role in GBM progression by activating the p-AKT-MYC signaling pathway. LPCAT1 activated AKT, which were synchronously up-regulated MYC to accelerate cancer progression. Knockdown of LPCAT1 induced the opposite changes to repress the viability and motility of GBM cells. LPCAT1 contributed to the progression of GBM by participating in the p-AKT-MYC axis.

Development of a Cancer-associated Fibroblast Signature for Evaluating Immunotherapy Response and Prognosis of Hepatocellular Carcinoma.

Alcohol abuse, non-alcoholic fatty liver disease (NAFLD), and hepatitis B and C are the main pathogenic factors of hepatocellular carcinoma (HCC). Though the current understanding of risk factors for HCC has been improved, patients with this type of cancer are normally diagnosed at advanced stages, posing significant challenges to effective treatment. This study analyzed the HCC datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database (GSE14520 and GSE116174). Stromal and immune cell infiltration in the tumor microenvironment (TME) was quantified by the ESTIMATE algorithm. To identify gene modules associated with cancer-associated fibroblasts (CAFs), weighted gene co-expression network analysis (WGCNA) was performed to develop gene co-expression networks. A CAF prognosis score (CAFPS) model was established based on the prognostic CAF genes screened by univariate and multivariate Cox regression analyses. To determine the role of the genes in the vital module in HCC, we conducted Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Finally, the relationship between CAFPS and drug sensitivity was analyzed using Genomic Data for Cancer Drug Sensitivity (GDSC). In this study, we found significant differences in immune scores, stromal scores, CAFs scores, and CD4/8 T-cell scores between normal samples and samples with different TNM staging. In particular, the proportion of CAFs was higher than all other cells in normal samples. Gene modules related to CAFs were identified by developing a gene co-expression network using WGCNA analysis. The lightyellow and greenyellow modules showed the highest correlation with CAF scores. Univariate COX analysis identified 12 genes related to HCC prognosis from a total of 191 genes in the two modules. The Kaplan-Meier (KM) survival analysis revealed that a high expression of these genes was associated with a lower survival chance. Based on the 12 genes obtained by univariate COX analysis, multivariate COX analysis was performed to construct a risk score model for the characteristics of CAFs (CAFPS). The KM survival curves of patients in the high CAFPS and low CAFPS groups showed that patients in the low CAFPS group had better survival. CAFs played a crucial role in the pathogenesis and treatment response of HCC. Targeting the CAFs milieu may provide therapeutic benefits, highlighting the importance of CAFS in developing a personalized treatment for HCC patients. Further studies are required to verify the current findings and explore their implications in clinical settings.

Previous arthroscopy does not decrease survivorship or functional outcomes for unicompartmental knee arthroplasty patients.

Arthroscopic procedures for osteoarthritis (OA), in particular arthroscopic meniscectomy, have poorer long-term clinical outcomes compared to those managed non-operatively. In addition, previous arthroscopy is associated with worse outcomes following subsequent total knee arthroplasty (TKA), however there is limited data on the impact on subsequent unicompartmental knee arthroplasty (UKA) outcomes. The aim of the study is to investigate whether patients who had arthroscopy prior to UKA have differences in survivorship or functional outcomes compared to those with no prior arthroscopy. All patients who received either a primary medial or lateral UKA at four large tertiary hospitals were included (n = 2,272). Patient data (age, sex, ethnicity, body mass index (BMI), American Society of Anesthesiologists (ASA) status and surgical data) was recorded following systematic review of all clinical notes and radiographs. Differences between survival curves were analysed using log-rank curves. Differences between categorical data was compared using Fisher's exact or Chi-squared tests, and differences between continuous variables were compared using t-tests. There was no difference between the survival curves for UKA patients with previous arthroscopy compared to those with no previous arthroscopy (10 years: 91% UKA with previous arthroscopy vs. 92% no previous arthroscopy; 15 years: 78% previous arthroscopy vs. 86% no previous arthroscopy; p = 0.50). Oxford Knee Score (OKS) was comparable between patients who had previous arthroscopy and those who had no previous arthroscopy at 6 months (38.8 vs. 39.3, p = 0.45), 5 years (42.0 vs. 40.4, p = 0.11) and 10 years (40.8 vs. 40.2, p = 0.71). In this large patient cohort with comprehensive review of clinical data and outcomes, we found that prior arthroscopy did not affect survivorship or functional outcomes of UKA patients.

HnRNP Q/SYNCRIP interacts with LIN28B and modulates the LIN28B/let-7 axis in human hepatoma cells.

The RNA-binding protein LIN28B represses the biogenesis of the tumor suppressor let-7. The LIN28B/let-7 axis regulates cell differentiation and is associated with various cancers. The RNA-binding protein Q (hnRNP Q) or SYNCRIP (Synaptotagmin Binding Cytoplasmic RNA Interacting Protein) has been implicated in mRNA splicing, mRNA transport, translation, and miRNAs biogenesis as well as metabolism in cancer. To determine whether hnRNP Q plays a role in the LIN28B/let-7 axis, we tested for interactions between hnRNP Q and LIN28B. We demonstrated that hnRNP Q interacts with LIN28B in an RNA-dependent manner. Knockdown of hnRNP Q caused reduced expression of a well-known let-7 target TRIM71, an E3 ubiquitin ligase that belongs to the RBCC/TRIM family, and also LIN28B, whose mRNA itself is down-regulated by let-7. In addition, hnRNP Q knockdown increased let-7 family miRNA levels and reduced the activity of luciferase reporters fused with the TRIM71 3'UTR or a synthetic 3'UTR carrying 8X let-7 complementary sites. Finally, depletion of hnRNP Q inhibited the proliferation of a hepatocellular carcinoma cell line, Huh7. This observation is consistent with the survival curve for liver cancer patients from the TCGA database, which indicates that high expression of hnRNP Q is a prognostic marker for a poor outcome in individuals afflicted with hepatocellular carcinoma. Together, our findings suggest that hnRNP Q interacts with LIN28B and modulates the LIN28B/let-7 axis in hepatocellular carcinoma.

Automated digital oncologic data review for breast cancer research: AI-enabled mCODE and field-of-interest extraction framework.

e12647 Background: Enhancing outcomes in cancer care and research can be optimally achieved by accelerating data extraction from unstructured electronic health resources. Understanding the association between treatment response markers and long-term outcomes is crucial for refining cancer therapeutic approaches and improving patient prognosis. In this study, we explore the association of oncologic outcomes with pathologic complete response (pCR) in high-risk early-stage breast cancer treated with neoadjuvant chemotherapy (NACT) using automated oncologic data extraction framework. Methods: Patients with primary stage I-III breast cancer who received NACT followed by mastectomy, with or without immediate breast reconstruction from January 2010 to August 2023 were retrospectively analyzed. We extracted pCR results and data on clinical and pathological stage, tumor subtype, grade, and treatment regimens and factors affecting postoperative complications from electronic medical records based on the AI enabled-mCODE (Minimal Common Oncology Data Elements) and fields of interest extraction framework. Employing mixed-effects Cox models, we explored the association between pCR and event-free survival (EFS), distant recurrence free Survival (DRFS) and overall survival (OS). Survival curves of patients were estimated using Kaplan-Meier method. Multivariate analysis was performed to evaluate the predictive factors for pCR. Results: Overall, 2725 patients were analyzed. The median age was 50.6 years. The median follow-up was 67 months. pCR was achieved in 31.0%. Hazard ratio for pCR vs. non-pCR were 0.34 for EFS (95% CI, 0.25-0.45), 0.32 for DRFS (95% CI, 0.23-0.43), 0.21 for OS (95% CI, 0.13-0.34), varying from 0.13 to 0.56 for EFS, 0.12 to 0.48 for DRFS and 0.07 to 0.40 for OS. The presence of pCR remained prognostic for event-free survival in multivariate models adjusted for age, tumor size, and nodal status at baseline. Conclusions: This study confirms that patients achieving pCR after NACT have better long-term survival outcomes that patients who do not. Oncologic data extraction from unstructured electronic medical records using AI-enabled extraction framework can be expected to enhance robust cancer research and generate valuable insights from real-world practice settings for tailored therapeutic decision-making. [Table: see text]

MELD3.0 is superior to MELDNa and MELD for prediction of mortality in patients with cirrhosis: An external validation in a multi-ethnic population.

The model for end-stage liver disease (MELD) was updated to MELDNa and recently to MELD3.0 to predict survival of cirrhotic patients. We validated the prognostic performance of MELD3.0 and compared with MELDNa and MELD amongst cirrhotic inpatients. Demographical, clinical, biochemical, and survival data of cirrhotic inpatients in Singapore General Hospital (SGH) from 01 January 2018 to 31 December 2018, were studied retrospectively. Patients were followed up from first admission in 2018 until death or until 01 April 2023. Area under the receiver operating characteristic curves (AUROC) were computed for the discriminative effects of MELD3.0, MELDNa, and MELD to predict 30-, 90-, and 365-day mortalities. AUROC was compared with DeLong's test. The cutoff MELD3.0 score for patients at high risk of 30-day mortality was determined using Youden's Index. Survival curves of patients with MELD3.0 score above and below the cutoff were estimated with Kaplan-Meier method and compared with log-rank analysis. Totally 862 patients were included (median age 71.0 years [interquartile range, IQR: 64.0-79.0], 65.4% males, 75.8% Chinese). Proportion of patients with Child-Turcotte-Pugh classes A/B/C were 55.5%/35.5%/9.0%. Median MELD3.0/MELDNa/MELD scores were 12.2 (IQR: 8.7-18.3)/11.0 (IQR: 8.0-17.5)/10.3 (IQR: 7.8-15.0). Median time of follow-up was 51.9 months (IQR: 8.5-59.6). The proportion of 30-/90-/365-day mortalities was 5.7%/13.2%/26.9%. AUROC of MELD3.0/MELDNa/MELD in predicting 30-, 90-, and 365-day mortalities, respectively, were 0.823/0.793/0.783, 0.754/0.724/0.707, 0.682/0.654/0.644 (P < 0.05). Optimal cutoff to predict 30-day mortality was MELD3.0 > 19 (sensitivity = 67.4%, specificity = 82.4%). Patients with MELD3.0 > 19, compared with patients with MELD3.0 ≤ 19, had shorter median time to death (98.0 days [IQR: 28.8-398.0] vs 390.0 days [IQR: 134.3-927.5]), and higher proportion of 30-day mortality (68.8% vs 43.0%) (P < 0.001). MELD3.0 performs better than MELDNa and MELD in predicting mortality in cirrhotic inpatients. MELD3.0 > 19 predicts higher 30-day mortality.

Sarcopenia is a possible risk factor for amputation after peripheral arterial interventions.

Sarcopenia has been demonstrated to be related to unfavorable clinical outcomes in patients with vascular diseases. The purpose of this study is to evaluate the relationship between sarcopenia and clinical results in patients with peripheral arterial disease who underwent endovascular therapy (EVT). This single-center retrospective study involved patients with PAD who underwent peripheral EVT at Ankara City Hospital, between January 2018 and December 2021. Two groups of patients were created: sarcopenic and non-sarcopenic patients according to computed tomography angiography muscle measurements. Primary outcome measures were major and minor amputation and survival. Mortality, amputation, and clinical characteristics were compared between the two patient groups. Hazard ratios (HRs) for amputation were calculated for each risk factor via univariate and multivariate analyses. Secondary outcomes included length of hospital stay and post-procedural complications. The mean follow-up period was 29.9 ± 9months for all patients. A total number of 100 patients (mean age 63.5 ± 9.2years) were involved in the study cohort. A significant association was identified between mortality and sarcopenia (p < .001). The mortality rate in the group with sarcopenia was significantly higher than the other group; 65.7% (23 patients) versus (20%, 13 patients) (p < .001). The major amputation rate in the group with sarcopenia was 57.1%, the major amputation rate in the group without sarcopenia was calculated as 15.4%, revealing that the major amputation rate was detected to be significantly higher in the sarcopenia group (p < .001). Multivariate regression analyses showed that only sarcopenia (HR, 0.52; 95% CI, 0.21-1.27; p = 0.15) was independently associated with major amputation in patients with PAD after EVT. Kaplan-Meier analysis revealed a statistically significant difference between the survival curves of sarcopenia and non-sarcopenia patients (p < .001). Sarcopenia seems to be a possible risk factor associated with amputation in patients with PAD who undergo EVT. The results of this study imply that sarcopenia is a possible risk factor for overall survival in patients with PAD.

Establishment of artificial intelligence model for precise histological subtyping of lung adenocarcinoma and its application to quantitative and spatial analysis.

The histological subtype of lung adenocarcinoma is a major prognostic factor. We developed a new artificial intelligence model to classify lung adenocarcinoma images into seven histological subtypes and adopted the model for whole-slide images to investigate the relationship between the distribution of histological subtypes and clinicopathological factors. Using histological subtype images, which are typical for pathologists, we trained and validated an artificial intelligence model. Then, the model was applied to whole-slide images of resected lung adenocarcinoma specimens from 147 cases. The model achieved an accuracy of 99.7% in training sets and 90.4% in validation sets consisting of typical tiles of histological subtyping for pathologists. When the model was applied to whole-slide images, the predominant subtype according to the artificial intelligence model classification matched that determined by pathologists in 75.5% of cases. The predominant subtype and tumor grade (using the WHO fourth and fifth classifications) determined by the artificial intelligence model resulted in similar recurrence-free survival curves to those determined by pathologists. Furthermore, we stratified the recurrence-free survival curves for patients with different proportions of high-grade components (solid, micropapillary and cribriform) according to the physical distribution of the high-grade component. The results suggested that tumors with centrally located high-grade components had a higher malignant potential (P<0.001 for 5-20% high-grade component). The new artificial intelligence model for histological subtyping of lung adenocarcinoma achieved high accuracy, and subtype quantification and subtype distribution analyses could be achieved. Artificial intelligence model therefore has potential for clinical application for both quantification and spatial analysis.

Improved overall survival in patients developing endocrine toxicity during treatment with nivolumab for advanced non-small cell lung cancer in a prospective study

PurposeImmune checkpoint inhibitors (ICPIs) disrupting PD-1/PD-L1 axis have revolutionized the management of advanced non-small cell lung cancer (NSCLC). Some studies identified the development of endocrine toxicity as predictor of better survival in cancer patients treated with ICPIs. The aim of study was to evaluate survival and new onset of immune-related endocrine adverse events (irAEs) in patients treated with nivolumab for advanced NSCLC.MethodsIn a prospective study, 73 patients with previously treated advanced NSCLC received nivolumab in monotherapy. Blood samples were collected at each cycle to monitor thyroid autoimmunity, thyroid, adrenal and somatotroph axes, while thyroid morphology was evaluated by ultrasonography.ResultsAn impaired thyroid function was recorded in 23.4% of patients (n = 15). Eight patients developed asymptomatic transient thyrotoxicosis (ATT) evolving to hypothyroidism in 50% of cases. In addition, seven patients developed overt hypothyroidism without ATT and with negative autoantibodies. Patients who developed hypothyroidism proved to have better overall survival (OS) as compared with non-developers at both univariate (p = 0.021) and multivariate analyses (p = 0.023). The survival curve of patients with reduced IGF-I at baseline, or displaying its reduction during the follow-up, showed significantly reduced median survival compared to patients with normal/high IGF-I levels (p = 0.031).ConclusionsThyroid function abnormalities are the major irAEs in patients treated with nivolumab, and hypothyroidism onset is associated with prolonged survival. Our findings indicate that the development of hypothyroidism is a positive predictive biomarker of nivolumab antitumor efficacy in patients with NSCLC. Low IGF-I levels could represent a negative prognostic factor during nivolumab therapy.

The effectiveness of treatment depending on an adherence to dispensary observation and antiretroviral therapy in patients with HIV infection

Aim. Determination of the causes of deaths and analysis of the survival of people living with HIV, depending on an adherence to dispensary observation and treatment. Materials and methods. The analysis of socio-demographic characteristics and clinical and laboratory data of 284 adult HIV patients observed in 1999–2011 at the Lomonosov Interdistrict Hospital named after I. N. Yudchenko was carried out. Patients who followed the prescribed monitoring regimen (at least 2 times a doctor’s visit during the year) were considered committed to dispensary supervision. Patients who observed the regularity and continuity of monitoring and receiving antiretroviral therapy (ART) were considered committed to treatment. Among the patients included in the study, 115 people were committed to treatment or follow-up and 169 patients were non-committed. Objective (biological) indicators of adherence and effectiveness of treatmentwere the number of CD4 lymphocytes and the level of HIV viral load. Based on the method of comparing survival curves, factors related to the life expectancy of HIV patients were assessed, taking into account the gender of patients, their adherence to monitoring and treatment, indicators of HIV viral load and the number of CD4 lymphocytes and the outcome of the disease from the moment of registration at the dispensary and over the next 120 months (after 3 months, 6 months, 1.5 years, 2 years, 5, 7 and 10 years). Results and discussion. Significant differences were found in the survival curves of patients who received and did not receive ART (117.9 and 91.4 months, p&lt;0.005) and patients who were committed and non-committed to therapy (116.9 and 83.8 months, p&lt;0.005). Regardless of adherence to outpatient follow-up and therapy, the survival time of women compared to men for the entire follow-up period was longer (105.0 and 92.4 months, respectively, p&lt;0.005). Among those committed to treatment, 21% of patients died due to concomitant somatic pathology, 5% from injuries incompatible with life. In the group of those committedto follow–up, the causes of deaths in 12% were various somatic pathology, brain lymphoma — in 1% and injuries incompatible with life — in 3% of cases. The highest mortality rates were recorded among patients who were not exposed to ART (71%) and the routine of follow-up (52%). Almost half of these patients (49%) died from secondary HIV infections, of which 85% of cases were posthumously diagnosed with tuberculosis, mainly the pulmonary form of the disease. The second most common cause of death was violent death, including drug poisoning. Conclusion. Regular dispensary observation, timely initiation of ART and adherence to therapy make it possible to control the disease, prevent the development of opportunistic pathology, and improve the quality and life expectancy of patients with HIV infection. Despite the increased availability of ART and strategies for active involvement and retention of patients in dispensary care, issues of patient adherence to therapy remain key in the management of HIV patients.

A preliminary study of optimal treatment response rates in patients undergoing hepatic arterial infusion chemotherapy combined with molecular targeting and immunotherapy.

This study aimed to examine the effectiveness of the best response rate (BRR) as a surrogate for overall survival (OS), using the modified Response Evaluation Criteria in Solid Tumors (mRECIST), in patients with unresectable hepatocellular carcinoma (HCC) undergoing hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) combined with molecular targeting and immunotherapy. This study enrolled 111 consecutive patients who had complete imaging data. The median age of patients was 58 years (IQR 50.5-65.0). Among the patients, those with Barcelona Clinic Liver Cancer (BCLC) stage A, BCLC stage B, and BCLC stage C comprised 6.4%, 19.1%, and 73.6%, respectively. The optimal threshold of BRR can be determined using restricted cubic splines (RCS) and the rank sum statistics of maximum selection. Survival curves of patients in the high rating and low rating groups were plotted. We then used the change-in-estimate (CIE) method to filter out confounders and the inverse probability of treatment weighting (IPTW) to balance confounders between the two groups to assess the robustness of the results. The median frequency of the combination treatment regimens administered in the overall population was 3 times (IQR 2.0-3.0). The optimal BRR truncation value calculated was -0.2. Based on this value, 77 patients were categorized as the low rating group and 34 as the high rating group. The differences in the OS between the high and low rating groups were statistically significant (7 months [95%CI 6.0-14.0] vs. 30 months [95%CI 30.0-]; p< 0.001). Using the absolute 10% cut-off value, the CIE method was used to screen out the following confounding factors affecting prognosis: successful conversion surgery, baseline tumor size, BCLC stage, serum total bilirubin level, number of interventional treatments, alpha-fetoprotein level, presence of inferior vena cava tumor thrombus, and partial thrombin activation time. The survival curve was then plotted again using IPTW for confounding factors, and it was found that the low rating group continued to have better OS than the high rating group. Finally, the relationship between BRR and baseline factors was analyzed, and inferior vena cava tumor thrombus and baseline tumor size correlated significantly with BRR. BRR can be used as a surrogate endpoint for OS in unresectable HCC patients undergoing FOLFOX-HAIC in combination with molecular targeting and immunotherapy. Thus, by calculating the BRR, the prognosis of HCC patients after combination therapy can be predicted. Inferior vena cava tumor thrombus and baseline tumor size were closely associated with the BRR.

Prognostic difference between surgery and external radiation in patients with stage I liver cancer based on competitive risk model and conditional survival rate.

This study aimed to assess the difference in prognosis of patients with early-stage liver cancer after surgery or external radiation. Between 2010 and 2015, 2155 patients with AJCC 7th stage I liver cancer were enrolled in the SEER database. Among these, 1972 patients had undergone surgery and 183 had undergone external beam radiation. The main research endpoints were overall survival (OS) and disease-specific survival (DSS). The competitive risk model was used to calculate the risk ratio of liver cancer-specific deaths when there was a competitive risk. Propensity Score Matching (PSM) method using a 1:1 ratio was used to match confounders such as sex, age, and treatment method. Conditional survival was dynamically assessed for patient survival after surgery or external radiation. Multivariate analysis of the competitive risk model showed that age, disease diagnosis time, grade, and treatment [surgery and external beam radiation therapy (EBRT)] were independent prognostic factors for patients with hepatocellular carcinoma. Surgery had a higher survival improvement rate than that of EBRT. As the survival of patients with liver cancer increased, the survival curve of surgery declined more slowly than that of radiotherapy patients and stabilized around 3 years after surgery. The survival curve of radiotherapy patients significantly dropped within 4 years and then stabilized. Surgery was better than EBRT for patients with stage I liver cancer. Close follow-up was required for 3 years after surgery or 4 years after external radiation. This study can help clinicians make better informed clinical decisions.

Abstract 5205: Beyond boundaries: ADRB3, a novel prognostic marker in pediatric neuroblastoma

Abstract Introduction: Neuroblastoma (NB) is a pediatric tumor arising from immature nerve cells originating from neural crest cells. This malignancy is characterized by a remarkably early onset, with only 10% of cases occurring beyond 5 years of age. According to the INRG classification, ~50% of patients are classified as low risk (L1/L2). Despite advances in treatment, around 20% of these experienced a relapse within 5 years with a mere 10% survival rate. Methods: We investigated the role of the adrenoceptor beta-3 (ADRB3) as a prognostic factor for NB. The samples provided by IRCCS Meyer Children’s Hospital allowed us to measure cytofluorimetric level expression of ADRB3 in tissue biopsies from 43 NBs, in the circulating tumor cells (CTCs) and in the bone marrow cells (BMCs) at onset and at the end of treatment. Further, to study the role of ADRB3 in NB, we used CRISPR-Cas9 to knock down ADRB3 expression in mice model. Results: Results indicate that ADRB3 levels in biopsy at the onset are significantly higher (Wilcoxon test, p = 0.026) in patients with negative outcome than those who achieved complete remission. The R package survival was used to perform Survival curve analysis to further assess the impact of ADRB3 at the onset in biopsy tissues. Results confirmed a significant separation (p = 0.031) between survival curves of patients with high levels and those with low levels, reinforcing its importance as a prognostic factor. Moreover, the same results were found in survival curves (p = 0.038) in low-risk patients, corroborating the importance of ADRB3 levels to discriminate between unfavorable or favorable prognosis. Moreover, post-chemotherapeutic treatment analysis, in both residual CTCs and BMCs, indicated statistically differences in ADRB3 levels between fully recovered patients and deceased. Survival curves, stratified by ADRB3 levels in CTCs post-chemotherapy, a favorable prognosis for patients with low levels (p = 0.0001). Finally, the expression analysis showed that ADRB3 levels in NB cells led to increment of processes associated with the cellular migration and metastasization and in metabolism. Conclusion: Our findings suggest that ADRB3 is a significant prognostic factor for NB. Patients with high ADRB3 expression in biopsy at the onset and after the treatment have a higher risk of unfavorable outcome, even for low-risk patients. In conclusion, our results challenge current classification and prognostic paradigms, highlighting ADRB3's crucial role in NB, contributing to refine risk stratification and unveil a new potential target for liquid biopsy of detecting, analyzing and monitoring CTCs. Citation Format: Gianluca Mattei, Cristina Banella, Francesco Carrozzo, Amada Pasha, Annalisa Tondo, Claudio Favre, Maura Calvani. Beyond boundaries: ADRB3, a novel prognostic marker in pediatric neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5205.