Prognostic Factors For Survival Research Articles

Abstract A157: Age-related disparities in survival following colorectal cancer diagnosis in an underserved community in Georgia

Abstract Background: Significantly higher colorectal cancer (CRC) mortality exists in Augusta-Richmond County of Georgia, an area with a large proportion of underserved African Americans. Although age is one of the most important prognostic factors in cancer survival, age disparities in survival following CRC diagnosis have been understudied within geographic areas of Georgia. Thus, we examined overall survival (OS) rates following CRC diagnosis between 18-49, 50-59, 60-69, and 70+ age groups. We also determined whether age-specific differences were associated with OS and examined factors contributing to OS across these four age groups in a cancer center population in Augusta-Richmond County. Methods: A retrospective cohort analysis was performed using 2012-2022 data from the Georgia Cancer Center cancer registry linked with electronic medical records and billing data. OS following CRC diagnosis was the outcome of interest; those who survived until 2023 were censored. Cox proportional hazard regression was used to examine the mentioned associations in different age groups adjusted for sociodemographic characteristics (gender, race, marital status, insurance, county-level poverty), health-related factors (body mass index, smoking status, alcohol use, chronic disease conditions, family history of CRC/cancer), tumor characteristics (tumor grade, stage at diagnosis, primary site), and diagnosis year. Results: Among 839 CRC patients, OS rates were lowest among patients aged 70+ years (52.8%) followed by 60-69 (61.2%), 18-49 (63.7%), and 50-59 (65.2%) years (p <0.001). In the adjusted analysis, CRC patients aged 70+ years had a 2.1-fold increased risk of death due to all causes compared to those aged 18-49 years (HR, 2.1; 95% CI, 1.2-3.7). Regardless of age groups, CRC patients with a late stage at diagnosis were associated with increased risk of all causes of death by 2.0-5.7 times (18-49 year: HR, 4.9; 95% CI,2.7-8.8; 50-59 year: HR, 5.7; 95% CI,3.6-9.0; 60-69 year: HR, 5.3; 95% CI, 3.5-8.0; 70+ year: HR,2.0; 95% CI,1.3-3.0). Among patients aged 60-69 years, those living in poverty areas had an increased risk of all causes of death by 1.8-times (HR, 1.8; 95% CI, 1.2-2.7). However, having private insurance (HR, 0.3; 95% CI,0.2-0.5) was associated with lower risk of mortality by 69% for 50- 59 age group. Conclusion: Patients aged 70+ years reported lower OS rates. Late stage at diagnosis was strongly associated with increased risk of death regardless of age; significantly greater risk was observed at 50-59 age group followed by 60-69, 18-49, and 70+ age groups. In particular, poverty had an negative impact on the risk of death following CRC diagnosis for the 60-69 age group. The high mortality among patients aged 50 and older emphasizes the need for developing strategies for increasing the screening uptake and starting at earlier ages, particularly among the most vulnerable populations. Equally important are strategies to improve access to screening and treatment resources for patients with limited access to healthcare. Citation Format: Meng-Han Tsai, Jorge Cortes, Marlo Vernon, Elinita Pollard, Steven S. Coughlin, Yanbin Dong, Kenneth J. Vega. Age-related disparities in survival following colorectal cancer diagnosis in an underserved community in Georgia [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A157.

The impact of histological subtype on postoperative recurrence pattern and timing in locally advanced esophagogastric junction cancer

PurposeThe differences in tumor behavior between adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the esophagogastric junction (EGJ) have yet to be well investigated. The purpose of this study was to gain insights that can contribute to tailored treatments and follow-up strategies by analyzing the correlation between histological subtypes and oncological outcomes.MethodsA retrospective analysis was used to determine the characteristics of the histological subtypes of EGJ cancer by comparing the appearance of postoperative recurrence. A total of 102 consecutive patients with pathological stage IIA to IVA EGJ cancer, who underwent R0 surgery in our department from 2004 to 2020, were enrolled. The recurrence pattern, timing, survival, and potential prognostic factors were compared.ResultsAfter a median follow-up time of 70.1 months, the AC group demonstrated comparable lymph node failure-free survival (P = 0.291) and significantly worse non-lymphogenous recurrence-free survival (P = 0.035) than did the SCC group. A significantly longer period from surgery to recurrence was also observed in the AC group (P = 0.029). Multivariate analysis indicated that histological subtype (P = 0.015, 95% CI 1.24–7.28) was significantly correlated with the incidence of non-lymphogenous recurrence.ConclusionsThe pattern and timing of postoperative recurrence were significantly different between the histological subtypes of EGJ cancer. Compared with EGJ SCC, EGJ AC may have a greater tendency toward non-lymphogenous progression and a greater propensity for longer surgery-to-recurrence periods.

Discovery of GJC1 as a prognostic biomarker in glioma cells: insights into its cell-cycle relationship and differential expression in non-neuronal cells

BackgroundGliomas, originating from the most common non-neuronal cells in the brain (glial cells), are the most common brain tumors and are associated with high mortality and poor prognosis. Glioma cells exhibit a tendency to disrupt normal cell-cycle regulation, leading to abnormal proliferation and malignant growth. This study investigated the predictive potential of GJC1 in gliomas and explored its relationship with the cell cycle.MethodsRetrospective analysis of RNA-seq and single-cell sequencing data was conducted using the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. The differential expression of GJC1 in gliomas with various pathological features and in different non-neuronal cell groups was analyzed. Functional data were examined using gene set variation analysis (GSVA). Furthermore, CellMiner was used to evaluate the relationship between GJC1 expression and predicted treatment response across these databases.ResultsGJC1 expression was enriched in high-grade gliomas and 1p/19q non-codeletion gliomas. GJC1 enrichment was observed in classical and mesenchymal subtypes within the TCGA glioma subtype group. In single-cell subgroup analysis, GJC1 expression was higher in glioma tissues compared to other non-neuronal cells. Additionally, the TCGA classical subtype of glioma cells exhibited more GJC1 expression than the other subgroups. GJC1 emerged as an independent prognostic factor for overall survival in glioma. GSVA unveiled potential mechanisms by which GJC1 may impact cell-cycle regulation in glioma. Finally, a significant correlation was observed between GJC1 expression and the sensitivity of multiple anti-cancer drugs.ConclusionThese findings confirmed GJC1 as a novel biomarker and provided insights into the differential gene expression in non-neuronal cells and the impact of the cell cycle on gliomas. Consequently, GJC1 may be used to predict glioma prognosis and has potential therapeutic value.

Expression and functional analyses of TERF2 in esophageal carcinoma

BackgroundEsophageal cancer (ESCA) is a prevalent malignancy with a high incidence of morbidity and mortality, particularly in Asia. Telomeric Repeat-binding Factor 2 (TERF2) is a crucial component of the telomere-binding protein complex that maintains telomere stability. Aberrant TERF2 expression has been implicated in tumorigenesis, however, its specific role in ESCA remains largely unexplored. MethodsThe expression levels of TERF2 were assessed in esophageal squamous cell carcinoma (ESCC) samples using RT-PCR, IHC, and Western blotting (WB). Serum tumor marker concentrations were determined via electrochemiluminescence immunoassay (ECLIA) and chemiluminescent microparticle immunoassay (CMIA). Bioinformatics analyses were employed to elucidate TERF2's function in EC. The impact of TERF2 on ESCC cell proliferation was evaluated through cell counting kit-8 (CCK8) assays and flow cytometry. ResultsTERF2 protein and mRNA expression were elevated in ESCC tissues and correlated with age, sex, cancer stage, tumor grade, lymph node metastasis (LNM), and tumor histology. Univariate Cox regression analysis indicated TERF2 was an independent prognostic factor for overall survival (OS). TERF2 mRNA levels were associated with serum levels of carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and tissue polypeptide antigen (TPA) in patients with ESCC. Immune infiltration and chemokine profiles were linked to TERF2 expression in ESCA. TERF2 is involved in regulating ESCC cell proliferation may through the DDR/P53 signaling way. ConclusionsTERF2 is overexpressed in ESCA and contributes to ESCC cell proliferation may via DDR/TP53 signaling pathway. These results suggest that TERF2 may serve as a potential target for developing treatments and diagnostic biomarker for ESCA.

Effect of Biliary Drainage on the Prognosis of Patients with Hepatocellular Carcinoma and Bile Duct Invasion.

Bile duct invasion (BDI) is rarely observed in patients with advanced hepatocellular carcinoma (HCC), leading to hyperbilirubinemia. However, the efficacy of pretreatment biliary drainage for HCC patients with BDI and obstructive jaundice is currently unclear. Thus, the aim of this study was to assess the effect of biliary drainage on the prognosis of these patients. We retrospectively enrolled a total of 200 HCC patients with BDI from multicenter cohorts. Patients without obstructive jaundice (n=99) and those who did not undergo HCC treatment (n=37) were excluded from further analysis. Finally, 64 patients with obstructive jaundice (43 subjected to drainage and 21 not subjected to drainage) were included. Propensity score matching was then conducted. The biliary drainage group showed longer overall survival (median 10.13 months vs 4.43 months, p=0.004) and progression-free survival durations (median 7.00 months vs 1.97 months, p<0.001) than the non-drainage group. Multivariate analysis showed that biliary drainage was a significantly favorable prognostic factor for overall survival (hazard ratio, 0.42; p=0.006) and progression-free survival (hazard ratio, 0.30; p<0.001). Furthermore, in the evaluation of first response after HCC treatment, biliary drainage was beneficial (p=0.005). Remarkably, the durations of overall survival (p=0.032) and progression-free survival (p=0.004) were similar after propensity score matching. Biliary drainage is an independent favorable prognostic factor for HCC patients with BDI and obstructive jaundice. Therefore, biliary drainage should be contemplated in the treatment of advanced HCC with BDI to improve survival outcomes.

Comparisons of clinical characteristics, treatments, and outcomes among different pathological subtypes of chondrosarcoma in the spine.

Spinal chondrosarcoma exhibits higher invasiveness and a worse prognosis compared to chondrosarcoma in the extremities. The prognosis and therapeutic plan vary greatly among different pathological subtypes of chondrosarcoma. This study aimed to analyze the differences in clinical characteristics, molecular features, therapeutic effects, and prognostic factors among the subtypes of chondrosarcoma in the spine. A retrospective review was conducted on 205 patients with spinal chondrosarcoma. The clinical features and immunohistochemical (IHC) markers were compared among the pathological subtypes of chondrosarcoma grade 1, grade 2, grade 3, mesenchymal chondrosarcoma (MCS), dedifferentiated chondrosarcoma (DCS), and clear cell chondrosarcoma (CCCS). Chondrosarcoma grade 1/2/3 are collectively referred to as conventional chondrosarcoma (CCS) for multivariate survival analysis. Univariate and multivariate analyses were performed to investigate independent prognostic factors for overall survival (OS) and recurrence-free survival (RFS) in patients with spinal chondrosarcoma. Furthermore, independent prognostic factors for OS and RFS were identified in CCS and MCS. MCS patients were younger than the other subtypes. Patients with chondrosarcoma grade 1/2 had better OS than those with chondrosarcoma grade 3, MCS and DCS, while only chondrosarcoma grade 1 patients showed better RFS than chondrosarcoma grade 2/3, MCS and DCS patients. Ki-67 index was higher in chondrosarcoma grade 3, MCS and DCS than chondrosarcoma grade 1/2. The comparison of IHC markers further highlighted the overexpression of P53/MDM2 in MCS and DCS. Gross total resection, including en-bloc and piecemeal resection, significantly improved OS and RFS for CCS patients, while only en-bloc resection significantly improved the prognosis of MCS patients. Chemotherapy appeared to be important for the OS of MCS patients. P53/MDM2 pathway was upregulated in MCS and DCS compared to chondrosarcoma grade 1/2. Radical tumor resection is crucial for the treatment of spinal chondrosarcoma, while MCS patients require further comprehensive treatments perioperatively.

METTL3-Mediated m6A Modification of FMRP Drives Hepatocellular Carcinoma Progression and Indicates Poor Prognosis.

Accumulating studies reveal that m6A RNA methylation plays a critical role in cancer pathogenesis and progression. METTL3 as a m6A methyltransferase acts as an oncogene in multiple malignancies including hepatocellular carcinoma (HCC). However, the role and underlying mechanism by which METTL3 contributes to HCC remain unclear. The association of METTL3 expression with clinicopathological characteristics and prognosis in patients with HCC was assessed by reverse transcription polymerase chain reaction, Western blot, and public TCGA dataset. MTT, colony formation, Transwell assays, and xenograft tumor models were executed to reveal the role of METTL3 in HCC. m6A dot blot, RNA immunoprecipitation (RIP), m6A methylated RIP, and Western blot assays were used to uncover the regulatory mechanism of METTL3 in HCC cells. We found that METTL3 was dramatically upregulated in HCC tissue samples and acted as an independent prognostic factor for poor survival and tumor recurrence in patients with HCC. Silencing of METTL3 repressed cell growth and invasion in vitro and invivo, but restored expression of METTL3 boosted these effects. Mechanistical investigations revealed that METTL3 could directly interact with FMRP and harbor a positive correlation with FMRP expression. Knockdown of METTL3 reduced FMRP m6A levels as well as its mRNA and protein expression. FMRP overexpression drove cell colony formation and cell invasion and abolished METTL3 knockdown-induced antitumor effects and AKT/mTORC1 signaling inactivation. Elevated expression of FMRP could act as an independent prognostic factor for poor survival and tumor recurrence in patients with HCC. Our findings demonstrate that METTL3-mediated m6A modification of FMRP promotes growth and invasion of HCC cells and may provide a promising therapeutic target for HCC.

Features and prognostic significance of soluble TIM-3 and its ligands Gal-9 and CEACAM1 levels in the diagnostic bone marrows of adult acute myeloid leukemia patients.

Prognostic significance of soluble immune checkpoint molecule TIM-3 and its ligands in the plasma has been illustrated in various solid tumors, but such study in newly diagnosed acute myeloid leukemia (AML) remains absent. Soluble TIM-3, Gal-9 and CEACAM1 levels in the bone marrow plasma samples collected from 90 adult AML patients at diagnosis and 12 healthy donors were measured by enzyme-linked immunosorbent assays (ELISA), and 16 AML patients were simultaneously tested cell membrane TIM-3 expression by multi-color flow cytometry. AML patients had significantly elevated soluble TIM-3 levels and similar soluble Gal-9 and CEACAM1 levels compared with healthy donors (p = 0.0003, 0.26 and 0.96). In the whole cohort, high soluble TIM-3 level was the sole independent adverse prognostic factor for relapse-free survival (RFS) (p = 0.0060), and it together with adverse ELN genetic risk were independent poor prognostic factors for event-free survival (EFS) (p = 0.0030 and 0.0040); High soluble CEACAM1 level were significantly related to lower RFS (p = 0.028). In addition, high soluble Gal-9 level had significant association with lower RFS in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the first complete remission (p = 0.037). Furthermore, soluble TIM-3 level tended to have positive correlation with the percentage of non-blast myeloid TIM-3+ cells in nucleated cells in AML (r = 0.48, p = 0.073). Therefore, the high soluble TIM-3 level in the diagnostic BM plasma predicted poor outcome in adult AML patients, and high sGal-9 level was associated with relapse after allo-HSCT.

Prognostic impact of interstitial lung disease on pulmonary high-grade neuroendocrine carcinoma

Pulmonary high-grade neuroendocrine carcinomas (HGNECs) have poor prognoses and require multimodal treatment, and interstitial lung disease (ILD) restricts sufficient treatment of patients with lung cancer. We aimed to clarify ILD’s prognostic impact on pulmonary HGNEC, which has previously gone unreported. We retrospectively analyzed 53 patients with HGNEC who underwent resections at our department between 2006 and 2021 and evaluated the clinicopathological prognostic features, including ILD. The patients’ mean age was 70 years; 46 (87%) were male, and all were smokers. Large-cell neuroendocrine and small-cell lung carcinomas were diagnosed in 36 (68%) and 17 (32%) patients, respectively. The pathological stages were stage I, II, and III in 31 (58%), 11 (21%), and 11 (21%) patients, respectively. Nine patients (17%) had ILD, which was a significant overall survival prognostic factor in a multivariate Cox proportional hazards regression analysis (p = 0.048), along with lymph node metastasis (p = 0.004) and non-administration of platinum-based adjuvant chemotherapy (p = 0.003). The 5 year survival rate of the ILD patients was 0%, significantly worse than that of patients without ILD (58.7%; p = 0.003). Patients with HGNEC and ILD had a poor prognosis owing to adjuvant therapy’s limited availability for recurrence and the development of acute exacerbations associated with ILD.

Value of CDR1-AS as a predictive and prognostic biomarker for patients with breast cancer receiving neoadjuvant chemotherapy in a prospective Chinese cohort

BackgroundNeoadjuvant chemotherapy (NAC) is an effective treatment for locally advanced breast cancer (BC). However, there are no effective biomarkers for evaluating its efficacy. CDR1-AS, well known for its important role in tumorigenesis, is a famous circular RNA involved in the chemosensitivity of cancers other than BC. However, the predictive role of CDR1-AS in the efficacy and prognosis of NAC for BC has not been fully elucidated. We herein aimed to clarify this role.MethodsThe present study included patients treated with paclitaxel-cisplatin-based NAC. The expression of CDR1-AS was detected by real-time quantitative reverse transcription polymerase chain reaction testing. The predictive value of CDR1-AS expression was examined in pathological complete response (pCR) after NAC using logistic regression analysis. The relationship between CDR1-AS expression and survival was demonstrated using the Kaplan–Meier method, and tested by log-rank test and Cox proportional hazards regression model.ResultsThe present study enrolled 106 patients with BC. Multivariate logistic regression analysis revealed that CDR1-AS expression was an independent predictive factor for pCR (odds ratio [OR] = 0.244; 95% confidence interval [CI] 0.081–0.732; p = 0.012). Furthermore, pCR benefits with low CDR1-AS expression were observed across all subgroups. The Kaplan–Meier curves and log-rank test suggested that the CDR1-AS high-expression group showed significantly better disease-free survival (DFS; log-rank p = 0.022) and relapse-free survival (RFS; log-rank p = 0.012) than the CDR1-AS low-expression group. Multivariate analysis revealed that CDR1-AS expression was an independent prognostic factor for DFS (adjusted HR = 0.177; 95% CI 0.034–0.928, p = 0.041), RFS (adjusted HR = 0.061; 95% CI 0.006–0.643, p = 0.020), and distant disease-free survival (adjusted HR = 0.061; 95% CI 0.006–0.972, p = 0.047).ConclusionsCDR1-AS may be a potential novel predictive biomarker of pCR and survival benefit in patients with locally advanced BC receiving NAC. This may help identify specific chemosensitive individuals and build personalized treatment strategies.

Long-term oncological outcomes after radical prostatectomy in a non-university teaching hospital

The evaluation of oncological outcomes after radical prostatectomy (RP) is a major component of quality control in prostate cancer (PCa) centres. To evaluate the oncological outcomes after RP in a non-university teaching hospital and compare them with other high-volume PCa centres. This study included 1,161 patients after RP who were divided into two risk groups. Low-risk: localised PCa (pT2) and prostate-specific antigen (PSA)≤ 20 ng/ml, Gleason score (GS) 6-7b and pN0. High-risk: locally advanced PCa (≥pT3a) and/or PSA >20 ng/ml and/or GS≥ 8 and/or pN1. Risk groups and clinicopathological features were correlated to biochemical recurrence (BCR)-free survival, cancer-specific survival (CSS) und overall survival (OS). The 10-year BCR-free survival, CSS und OS were 68.4%, 47.0% and 100% in the low-risk group and 87.4%, 89.0% and 73.9% in the high-risk group, respectively; the outcomes between risk groups were statistically significant (p<0.05). A multivariate Cox regression analysis was performed. GS was the most significant prognostic factor for CSS (p=0.00001) und BCR-free survival (p=0.00036). Nodal involvement (pN1) was strongly associated with CSS (p=0.00004). Age was the most important factor for overall survival in the high-risk group (p=0.0011). RP could be a curative treatment option for advanced PCa in selected cases. GS is the most important prognostic factor. Good oncological outcomes can also be achieved in non-university teaching hospitals.

The incidence of acute exacerbation of idiopathic pulmonary fibrosis: a systematic review and meta-analysis

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with a high incidence of acute exacerbation and an increasing mortality rate. Currently, treatment methods and effects are limited. Therefore, we conducted a meta-analysis of the incidence of acute exacerbation in patients with IPF, hoping to provide reference for the prevention and management of IPF. We systematically searched the PubMed, Embase, Cochrane Library and Web of Science databases. From the creation of the database to the cohort study on April 3, 2023, we collected studies on the incidence of acute exacerbation of IPF patients, and used Stata software (version 16.0) for meta analysis. We used the Newcastle Ottawa Quality Assessment Scale (NOS) to assess the risk of bias for each study. We calculated the incidence of acute exacerbation in IPF patients and analyzed the risk factors for acute exacerbation in IPF patients and prognostic factors for overall survival from the initial IPF diagnosis. A total of ten cohort studies on the incidence of AE-IPF were included, including 11,855 IPF patients. The results showed that the incidence of acute exacerbation within one year was 9%; the incidence of acute exacerbation within 2 years is 13%; the incidence of acute exacerbation within 3 years is 19%; the incidence of acute exacerbation within 4 years is 11%. In addition, one study reported an acute exacerbation rate of 1.9% within 30 days. The incidence of acute exacerbation within ten years reported in one study was 9.8%. Mura et al.'s article included a retrospective cohort study and a prospective cohort study. The prospective cohort study showed that the incidence of acute exacerbation within 3 years was 18.6%, similar to the results of the retrospective cohort study meta-analysis. Our system evaluation and meta-analysis results show that the incidence of AE-IPF is relatively high. Therefore, sufficient attention should be paid to the research results, including the management and prevention of the disease, in order to reduce the risk of AE.Trial registration: PROSPERO, identifier CRD42022341323.

The impact of preoperative treatments on the immune environment of rectal cancer.

To improve local disease control, the use of preoperative radiotherapy either alone or combined with chemotherapy has become standard practice in rectal cancer, but it is unclear how these treatments modify the antitumoral immune response. We aimed to evaluate tumor histopathologic features and the prognostic effect of host immune response in rectal cancer with variable treatment modalities. Ninety-five rectal cancers with short-course radiotherapy (SRT), 97 with long-course chemoradiotherapy (CRT), and 154 without preoperative treatments, were evaluated for histopathologic features including Crohn's-like reaction (CLR). CD3+ and CD8+ immunohistochemistry and tumor cells were analyzed from tumor tissue microarray samples to calculate T-cell densities and G-cross function values to estimate cancer cell-T-cell co-localization (proximity score). We found that lymphocyte densities were diminished after SRT, but CLR was scarcer after CRT. Proximity score and CLR density were prognostic for survival in cancer without preoperative treatments and could be combined into an enhanced prognostic score (immune grade). In the irradiated tumors, CLR density remained prognostic while the impact of T-cell infiltration was insufficient alone. In multivariable analysis, the immune grade proved to be an independent prognostic factor for survival. In conclusion, the immune contexture of rectal cancer harbors prognostic significance even after preoperative radiotherapy.

MRI-measured periprostatic to subcutaneous adipose tissue thickness ratio as an independent risk factor in prostate cancer patients undergoing radical prostatectomy

The purpose of this study is to evaluate whether the periprostatic adipose tissue thickness (PPATT) is an independent prognostic factor for prostate cancer patients after laparoscopic radical prostatectomy (LRP). This retrospective cohort study included consecutive prostate cancer patients who underwent LRP treatment at Wuhan Union Hospital from June 2, 2016, to September 7, 2023. PPATT was defined as the thickness of periprostatic fat and was obtained by measuring the shortest vertical distance from the pubic symphysis to the prostate on the midsagittal T2-weighted MR images. Subcutaneous adipose tissue thickness (SATT) was obtained by measuring the shortest vertical distance from the pubic symphysis to the skin at the same slice with PPATT. The primary outcome of the study was biochemical recurrence (BCR), and the secondary outcome was overall survival (OS). Multivariable Cox regression analysis was used to identify independent prognostic factors for prostate cancer survival and prognosis. Based on the optimal cutoff value, 162 patients were divided into a low PPATT/SATT group (n = 82) and a high PPATT/SATT group (n = 80). During the entire follow-up period (median 23.5 months), 26 patients in the high PPATT/SATT group experienced BCR (32.5%), compared to 18 in the low PPATT/SATT group (22.0%). Kaplan–Meier curve analysis indicated that the interval to BCR was significantly shorter in the high PPATT/SATT group (P = 0.037). Multivariable Cox regression analysis revealed that an increase in the PPATT/SATT ratio was associated with BCR (hazard ratio: 1.90, 95% CI, 1.03–3.51; P = 0.040). The PPATT/SATT ratio is a significant independent risk factor for BCR after LRP for prostate cancer patients.

Data-mining-based biomarker evaluation and experimental validation of SHTN1 for bladder cancer

BackgroundGene therapy in bladder cancer (BLCA) remains an area ripe for exploration. Recent studies have highlighted the crucial role of SHTN1 in the initiation and progression of various cancers and SHTN1 may have interacted with the FGFR gene. However, its specific function in BLCA remains unclear. Materials and methodsWe investigated the association between SHTN1 expression and prognosis, immune infiltration, and the tumor microenvironment (TME) across multiple malignancies using 433 BLCA samples from The Cancer Genome Atlas (TCGA). Differential gene expression analysis, functional annotation via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed for SHTN1-related genes by using R packages. Immune response and TME scores, along with drug sensitivity profiles of SHTN1, were analyzed using R packages. Immunohistochemistry (IHC) and western blotting were conducted to assess SHTN1 expression in surgical specimens from BLCA patients.CCK8 assay and cells wound healing assay were performed.The bioinformatics was analyzed by R software. Significant differences were evaluated using unpaired t test. ResultsSHTN1 expression levels were significantly elevated in BLCA associated with poor prognosis (p < 0.01). Receiver operating characteristic (ROC) curves and nomograms demonstrated the diagnostic and prognostic efficacy of SHTN1 in BLCA. Notably, SHTN1 expression was higher in high-grade BLCA compared to lower-grade (p = 5.6e-10), a finding corroborated by IHC and western blotting. Pathway enrichment analysis revealed significant involvement of the Neuroactive ligand-receptor interaction and Chemical carcinogenesis - DNA adducts signaling pathways among SHTN1 differentially expressed genes. In terms of immune infiltration, T cells CD8, T cells follicular helper, and dendritic cells were predominant in the SHTN1 low-expression group, whereas macrophages M0 and M2, and mast cells were predominant in the high-expression group. Multivariate Cox regression analysis identified SHTN1 as an independent prognostic factor for overall survival (HR = 2.93; 95 % CI = 1.40–6.13; p = 0.004).CCK8 and wound healing experiments showed that SHTN1 knockdown reduced the cell proliferation and migration. Western blot showed that the EMT pathway was clearly associated with SHTN1. ConclusionsOur findings suggest that SHTN1 holds promise as a prognostic and diagnostic biomarker for BLCA. Moreover, it is closely associated with elevated immune infiltration and distinct characteristics of the tumor microenvironment in BLCA.

Evaluation of a new scoring system for assessing nerve invasion in resected pancreatic cancer: A single-center retrospective analysis

Nerve invasion (NI) is a characteristic feature of pancreatic cancer. Traditional dichotomous statements on the presence of NI are unreasonable because almost all cases exhibit NI when sufficient pathological sections are examined. The critical implications of NI in pancreatic cancer highlight the need for a more effective criterion. This study included 511 patients, who were categorized into a training group and a testing group at a ratio of 7:3. According to the traditional definition, NI was observed in 91.2 % of patients using five pathological slides in our study. The prevalence of NI increased as more pathological slides were used. The criterion of ‘two points of intraneural (endoneural) invasion in the case of four pathological slides’ has the highest receiver operating characteristic (ROC) score. Based on this new criterion, NI was proved to be an independent prognostic factor for overall survival (OS) and disease-free survival (DFS) and was also correlated with tumor recurrence (P = 0.004). Interestingly, gemcitabine-based chemotherapy regimen is an independent favorable factor for patients with high NI. In the high NI group, patients who received a gemcitabine-based regimen exhibited a better prognosis than those who did not receive the gemcitabine-based regimen for OS (P = 0.000) and DFS (P = 0.001). In conclusion, this study establishes assessment criteria to evaluate the severity of NI in order to predict patient outcomes.

Enhanced platelet function through CAR-T cell therapy in relapsed/refractory multiple myeloma

The influence of chimeric antigen receptor T (CAR-T) cell therapy on platelet function in relapsed/refractory (R/R) multiple myeloma (MM) has not been thoroughly investigated. Our cohort comprised fifty MM patients treated with CAR-T cells. The mean platelet closure time (PCT) induced by collagen/adenosine diphosphate (CADP) in peripheral blood was significantly prolonged before lymphodepletion (195.24 ± 11.740 s) and notably reduced post-CAR-T cell therapy (128.02 ± 5.60 s), with a statistically significant improvement (67.22, 95% CI 46.91–87.53, P < 0.001). This post-treatment PCT was not significantly different from that of healthy controls (10.64, 95% CI 1.11–22.40, P > 0.05). Furthermore, a pronounced enhancement in PCT was observed in patients with a response greater than partial remission (PR) following CAR-T cell infusion compared to pre-treatment values (P < 0.001). An extended PCT was also associated with a less favorable remission status. In patients with cytokine release syndrome (CRS) grades 0–2, those with a PCT over 240.5 s exhibited a shorter progression-free survival (PFS), with median PFS times of 10.2 months for the PCT > 240.5 s group versus 22.0 months for the PCT ≤ 240.5 s group. Multivariate analysis revealed that a PCT value exceeding 240.5 s is an independent prognostic factor for overall survival (OS) in R/R MM patients after CAR-T cell therapy. The study demonstrates that CAR-T cell therapy enhances platelet function in R/R MM patients, and PCT emerges as a potential prognostic biomarker for the efficacy of CAR-T cell therapy.

The association between initial post-resuscitation diastolic blood pressure and survival after pediatric cardiac arrest: a retrospective study

BackgroundLimited research has analyzed the association between diastolic blood pressure (DBP) and survival after pediatric cardiopulmonary resuscitation (CPR). This study aimed to explore the association between post-resuscitation diastolic blood pressure and survival in pediatric patients who underwent CPR.MethodThis retrospective single-center study included pediatric patients admitted to the pediatric intensive care unit of Asan Medical Center between January 2016 to November 2022. Patients undergoing extracorporeal CPR and those with unavailable data were excluded. The primary endpoint was survival to ICU discharge.ResultsA total of 106 patients were included, with 67 (63.2%) achieving survival to ICU discharge. Multivariate logistic regression analysis identified DBP within 1 h after ROSC as the sole significant variable (p = 0.002, aOR, 1.043; 95% CI, 1.016–1.070). Additionally, DBP within 1 h demonstrated an area under the ROC curve of 0.7 (0.592–0.809) for survival to ICU discharge, along with mean blood pressure within the same timeframe.ConclusionOur study highlights the importance of DBP within 1-hour post-ROSC as a significant prognostic factor for survival to ICU discharge. However, further validation through further prospective large-scale studies is warranted to confirm the appropriate post-resuscitation DBP of pediatric patients.

319. EXTENSIVE LYMPHADENECTOMY MAY IMPROVE SURVIVAL IN NODE NEGATIVE OESOPHAGEAL CANCER

Abstract Background Lymph node metastases are a major prognostic factor in survival of patients with oesophageal cancer. The number of lymph nodes removed during oesophagectomy has been previously proven to be associated with improved survival. The aim of this study was to examine the effect of lymph node harvest on survival specifically in pathologically node negative (pN0) patients with oesophageal cancer. Methods Data were extracted from a prospectively populated single-surgeon database of oesophageal resections for cancer. All consecutive patients with pN0 were included. Patient-specific risk adjusted analysis of overall and disease-free survival was performed to identify the number of lymph nodes associated with improved survival. Results Inclusion criteria were met by 137 patients (49 squamous cell carcinoma and 88 adenocarcinoma). Adjusted for cancer stage, tumour (histological type, degree of differentiation, lympho-vascular invasion, neo-adjuvant therapy) and patient related factors (age, sex), increased lymph node number was associated with significant improvement in overall (P = 0.045) and disease free (P = 0.030) survival. Lymph node count ≥ 17 was associated with improved overall and disease-free survival. Conclusion In this cohort of patients with pathologically node-negative oesophageal cancer, lymph node count of 17 or above was associated with significantly improved survival.

Survival prognostic factors in nonsmall cell lung cancer patients with simultaneous brain metastases and poor performance status at initial presentation

PurposeAlthough the treatment of nonsmall cell lung cancer (NSCLC) has rapidly progressed recently, there is little evidence of treatment for patients with symptomatic brain metastases (BM) and poor performance status (PS). However, in symptomatic BM patients, appropriate upfront intracranial treatment can often lead to rapid improvement in PS and effective systemic therapy. Thus, this study investigated the prognostic factors for the survival of poor PS NSCLC patients with synchronous BM. MethodsData of patients with BM and Karnofsky PS (KPS) ≤70 at the first diagnosis of NSCLC who were treated in our hospital between January 2017 and December 2021 were reviewed. Patient survival was compared among patients stratified by type of first-line regimen of systemic treatment. Correlations between patient characteristics and survival were examined. ResultsFifty patients receiving aggressive treatment were enrolled. The median survival times for tyrosine kinase inhibitor (TKI), immune checkpoint inhibitor (ICI), and chemotherapy alone groups were 19 (95% confidence interval [CI], 2.8–68.5), 19 (3.0–62.0), and 13 (1.2–24.8) months, respectively. Survival in the TKI and ICI groups was significantly longer than in the chemotherapy alone group (p = 0.046, TKI vs. chemo; p = 0.022, ICI vs. chemo; p = 0.023). Both sex and type of systemic treatment correlated to survival time on univariate analysis. Chemotherapy alone for systemic treatment [p = 0.034; hazard ratio (HR), 0.44 (0.20–0.94)] remained significant for predicting overall survival in the multivariate analysis. ConclusionEven in patients with poor PS and BM at the initial diagnosis of NSCLC, the ICI group had a survival time comparable to that of the TKI group when combined with tailor-made intracranial treatment. There is a subgroup in the patient population that was previously considered unsuitable for ICI, whose PS improves with individualized intracranial treatment, and who may benefit from immunotherapy.