Independent Factor For Survival Research Articles

Predictive value of 18F-FDG PET/CT versus bone marrow biopsy and aspiration in pediatric neuroblastoma.

Neuroblastoma (NB) is the most prevalent solid extracranial malignancy in children, often with bone marrow metastases (BMM) are present. The conventional approach for detecting BMM is bone marrow biopsy and aspiration (BMBA). 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG PET/CT) has become a staple for staging and is also capable of evaluating marrow infiltration. The consensus on the utility of 18F-FDG PET/CT for assessing BMM in NB patients is still under deliberation. This retrospective study enrolled 266 pediatric patients with pathologically proven NB. All patients had pretherapy FDG PET/CT. BMBA, clinical, radiological, and follow-up data were also collected. The diagnostic accuracy of BMBA and 18F-FDG PET/CT was assessed. BMBAs identified BMM in 96 cases (36.1%), while 18F-FDG PET/CT detected BMI in 106 cases (39.8%) within the cohort. The initial sensitivity, positive predictive value (PPV), specificity, and negative predictive value (NPV) of 18F-FDG PET/CT were 93.8%, 84.9%, 90.6%, and 96.3%, respectively. After treatment, these values were 92.3%, 70.6%, 97.3%, and 99.4%, respectively. The kappa statistic, which measures agreement between BMBA and 18F-FDG PET/CT, was 0.825 before treatment and 0.784 after treatment, with both values indicating a substantial agreement (P = 0.000). Additionally, the amplification of MYCN and a positive initial PET/CT scan were identified as independent prognostic factors for overall survival (OS). 18F-FDG-PET/CT is a valuable method for evaluating BMM in NB. The routine practice of performing a BMBA without discrimination may need to be reassessed. Negative result from 18F-FDG-PET/CT could potentially spare children with invasive bone marrow biopsies.

The predictive value of next generation sequencing for matching advanced hepatocellular carcinoma patients to targeted and immunotherapy.

Targeted and Immunotherapy has emerged as a new first-line treatment for advanced hepatocellular carcinoma (aHCC). To identify the appropriate targeted and immunotherapy, we implemented next generation sequencing (NGS) to provide predictive and prognostic values for aHCC patients. Pretreatment samples from 127 HCC patients were examined for genomic changes using 680-gene NGS, and PD-L1 expression was detected by immunohistochemistry. Demographic and treatment data were included for analyses of links among treatment outcomes, drug responses, and genetic profiles. A prognostic index model for predicting benefit from treatment was constructed, taking into account of biomarkers, including TP53, TERT, PD-L1, and tumor mutation burden (TMB) as possible independent prognostic factors. The multivariate Cox regression analyses showed that PD-L1≥1% (HR 25.07, 95%CI 1.56 - 403.29, p=0.023), TMB≥5Mb (HR 86.67, 95% CI 4.00 - 1876.48, p=0.004), TERT MU (HR 84.09, 95% CI 5.23 - 1352.70, p=0.002) and TP53 WT (HR 0.01, 95%CI 0.00 - 0.47, p=0.022) were independent risk factors for overall survival (OS), even after adjusting for various confounders. A prognostic nomogram for OS was developed, with an area under the ROC curve of 0.91, 0.85, and 0.98 at 1-, 2-, and 3- year, respectively, and a prognostic index cutoff of 1.2. According to the cutoff value, the patients were divided into the high-risk group (n=29) and low-risk group (n=98). The benefit of targeted and immunotherapy in the low-risk group was not distinguishable according to types of agents. However, treatment of Atezolizumab and Bevacizumab appeared to provide longer OS in the high-risk group (12 months vs 9.2, 9, or 5 months for other treatments, p<0.001). The prognostic model constructed by PD-L1, TMB, TERT, and TP53 can identify aHCC patients who would benefit from targeted and immunotherapy, providing insights for the personalized treatment of HCC.

Metastasis patterns and prognosis in young gastric cancer patients: A propensity score‑matched SEER database analysis.

Whether young patients with metastatic gastric cancer (GC) had distinct metastasis patterns and survival outcomes from older patients remains controversial. The aim of the present study was to explore the metastasis patterns and prognostic factors in young patients and evaluate the survival outcome in comparison to their older counterparts. We identified patients with metastatic GC in the surveillance, epidemiology, and end results (SEER) database from 2010 to 2015. The patients were divided into two groups based on age at diagnosis: younger (≤40 years old) and older (>40 years old). We employed the chi-squared test to compare the clinicopathological characteristics between the two age groups. Furthermore, we conducted survival analyses using Kaplan-Meier and Cox regression analyses. To balance disparities in baseline characteristics, we employed propensity score matching (PSM). We identified 5,580 metastatic GC patients from the SEER database, with 237 (4.2%) classified as younger and 5343 (95.8%) as older patients. A total of 237 pairs of patients were generated after adjustment by PSM. Patients in the younger group exhibited a higher proportion of bone-only metastases and a lower proportion of liver-only metastases compared with patients in the older group. Multivariate Cox regression analysis demonstrated that youth was an independent protective factor for overall survival (OS) before and after PSM, but not for gastric cancer-specific survival (GCSS). Among the younger group, patients with liver-only metastasis demonstrated the best prognosis, whereas patients with lung-only metastasis exhibited significantly worse survival outcomes compared with liver-only metastases, even comparable to that of bone metastasis. Compared with the older group, the metastatic GC patients in the younger group exhibited more aggressive tumors but better prognoses. The metastasis pattern and its effect on the prognosis of GC varied by age group.

HSPA4 upregulation induces immune evasion via ALKBH5/CD58 axis in gastric cancer

IntroductionGastric cancer (GC) is one of the leading causes of cancer-related death worldwide. Recently, targeted therapies including PD1 (programmed cell death 1) antibodies have been used in advanced GC patients. However, identifying new biomarker for immunotherapy is still urgently needed. The objective of this study is to unveil the immune evasion mechanism of GC cells and identify new biomarkers for immune checkpoint blockade therapy in patients with GC.MethodsCoimmunoprecipitation and meRIP were performed to investigate the mechanism of immune evasion of GC cells. Cocuture system was established to evaluate the cytotoxicity of cocultured CD8+ T cells. The clinical significance of HSPA4 upregulation was analyzed by multiplex fluorescent immunohistochemistry staining in GC tumor tissues.ResultsHistone acetylation causes HSPA4 upregulation in GC tumor tissues. HSPA4 upregulation increases the protein stability of m6A demethylase ALKBH5. ALKBH5 decreases CD58 in GC cells through m6A methylation regulation. The cytotoxicity of CD8+ T cells are impaired and PD1/PDL1 axis is activated when CD8+ T cells are cocultured with HSPA4 overexpressed GC cells. HSPA4 upregulation is associated with worse 5-year overall survival of GC patients receiving only surgery. It is an independent prognosis factor for worse survival of GC patients. In GC patients receiving the combined chemotherapy with anti-PD1 immunotherapy, HSPA4 upregulation is observed in responders compared with non-responders.ConclusionHSPA4 upregulation causes the decrease of CD58 in GC cells via HSPA4/ALKBH5/CD58 axis, followed by PD1/PDL1 activation and impairment of CD8+ T cell’s cytotoxicity, finally induces immune evasion of GC cells. HSPA4 upregulation is associated with worse overall survival of GC patients with only surgery. Meanwhile, HSPA4 upregulation predicts for better response in GC patients receiving the combined immunotherapy.

Surgical options and survival prognosis in geriatric patients beyond average lifespan with locally advanced gastric cancer: a propensity score-matched analysis.

The appropriateness of laparoscopic gastrectomy (LG) for super-geriatric patients with locally advanced gastric cancer (LAGC) is inconclusive, and the prognostic factors are also yet to be elucidated. Herein, we aimed to investigate the surgical and oncological outcomes of LG versus open gastrectomy (OG) for geriatric patients with LAGC who have outlived the average lifespan of the Chinese population (≥ 78years). This is a monocentric, retrospective, comparative study. A 1:1 propensity score matching (PSM) was performed to minimize selection bias and ensure well-balanced characteristics. The primary endpoint of interest was 3-year overall survival, while secondary endpoints included procedure-related variables, postoperative recovery indices, and complications. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify unfavorable prognostic factors. Of 196 eligible individuals, 107 underwent LG and 89 underwent OG, with a median age (interquartile range [IQR]) of 82 [79, 84] years. PSM yielded 61 matched pairs, with comparable demographic and tumor characteristics. The LG group had a significantly lower overall complication rate than the OG group (31.1% vs. 49.2%, P = 0.042), as well as shorter duration of postoperative hospital stay [12 (11, 13) vs. 13 (12, 15.5) d, P < 0. 001], less intraoperative blood loss [95 (75, 150) vs. 230 (195, 290) mL, P < 0.001], but a longer operative time [228 (210, 255.5) vs. 196 (180, 219.5) min, P < 0.001]. The times to first aerofluxus, defecation, liquid diet, and half-liquid diet were comparable. Kaplan-Meier analyses revealed no significant difference in 3-year overall survival between the groups, either in the entire cohort or in subgroups with different TNM staging. Moreover, Age-adjusted Charlson Comorbidity Index scores of > 6 [hazard ratio (HR) 4.003; P = 0.021] and pathologic TNM stage III (HR 3.816, P = 0.023) were independent unfavorable prognostic factors for long-term survival. LG performed by experienced surgeons offers the benefits of comparable or better surgical and oncological safety profiles than OG for super-geriatric patients with LAGC.

CD137+ and regulatory T cells as independent prognostic factors of survival in advanced non-oncogene addicted NSCLC patients treated with immunotherapy as first-line

BackgroundImmune checkpoint inhibitors (ICIs), administered alone or combined with chemotherapy, are the standard of care in advanced non-oncogene addicted Non-Small Cell Lung Cancer (NSCLC). Despite these treatments' success, most long-term survival benefit is restricted to approximately 20% of patients, highlighting the need to identify novel biomarkers to optimize treatment strategies. In several solid tumors, immune soluble factors, the activatory CD137+ Tcells, and the immunosuppressive cell subsets Tregs and MDSCs (PMN(Lox1+)-MDSC and M-MDSCs) correlated with responses to ICIs and clinical outcomes thus becoming appealing predictive and prognostic factors. This study investigated the role of distinct CD137+ Tcell subsets, Tregs, MDSCs, and immune-soluble factors in NSCLC patients as possible biomarkers.MethodsThe levels of T cells, MDSCs and soluble factors were evaluated in 89 metastatic NSCLC patients who underwent ICIs as first- or second-line treatment. T cell analysis was performed by cytoflurimetry evaluating Tregs and different CD137+ Tcell subsets also combined with CD3+, CD8+, PD1+, and Ki67+ markers. Circulating cytokines and immune checkpoints were also evaluated by Luminex analysis. All these parameters were correlated with several clinical factors (age, sex, smoking status, PS and TPS), response to therapy, PFS , and OS . The analyses were conducted in the overall population and in patients treated with ICIs as first-line (naïve patients).ResultsIn both groups of patients, high levels of circulating CD137+ and CD137+PD1+ T cells (total, CD4 and CD8) and the soluble factor LAG3 positively correlated with response to therapy. In naïve patients, PMN(Lox1+)-MDSCs negatively correlated with clinical response, and a high percentage of Tregs was associated with favorable survival. Moreover, the balance between Treg/CD137+ Tcells or PMN(Lox1+)-MDSC/CD137+ Tcells was higher in non-responding patients and was associated with poor survival. CD137+ Tcells and Tregs resulted as two positive independent prognostic factors.ConclusionHigh levels of CD137+, CD137+PD1+ Tcells and sLAG3 could predict the response to ICIs in NSCLC patients independently by previous therapy. Combining the evaluation of CD137+ Tcells and Tregs also as Treg/CD137+ T cells ratio it is possible to identify naive patients with longer survival.

Impact of preoperative haemoglobin, albumin, lymphocyte, and platelet score on oral cancer prognosis.

To evaluate the preoperative haemoglobin, albumin, lymphocyte, and platelet score as a prognostic indicator in oral squamous cell carcinoma treated by radical surgery. Patients (83 men, 32 women; 65.80 ± 11.47 years) who underwent radical surgery between 2012 and 2022 were included. Factors affecting overall survival and disease-free survival according to the haemoglobin, albumin, lymphocyte, and platelet score were examined. Patients were categorised into low- and high-score groups using optimal cut-off values obtained from receiver operating characteristic curve analysis. The low-score group had poorer overall and disease-free survival (p < 0.001 each). Multivariate analysis identified alcohol consumption (hazard ratio [HR], 3.83; 95% confidence interval [CI]: 1.56-9.41, p = 0.003); vascular invasion (HR, 3.97; 95% CI: 1.60-9.85, p = 0.003); and the haemoglobin, albumin, lymphocyte, and platelet score (HR, 0.39; 95% CI: 0.20-0.78, p = 0.007) as independent prognostic factors for overall survival and vascular (HR, 3.66; 95% CI: 1.79-7.50, p < 0.001) and lymphovascular (HR, 2.44; 95% CI: 1.36-4.41, p = 0.003) invasion as independent prognostic factors for disease-free survival. The preoperative haemoglobin, albumin, lymphocyte, and platelet score may be a significant prognostic factor for patients with oral squamous cell carcinoma undergoing radical surgery.

Neoadjuvant chemotherapy is associated with suppression of the B cell-centered immune landscape in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed at advanced stages and associated with early distant metastasis and poor survival. Besides clinical factors, the tumor microenvironment (TME) emerged as a crucial determinant of patient survival and therapy response in many tumors, including PDAC. Thus, the presence of tumor-infiltrating lymphocytes and the formation of tertiary lymphoid structures (TLS) is associated with longer survival in PDAC. Although neoadjuvant therapy (NeoTx) has improved the management of locally advanced tumors, detailed insight into its effect on various TME components is limited. While a remodeling towards a proinflammatory state was reported for PDAC-infiltrating T cells, the effect of NeoTx on B cell subsets, including plasma cells, and TLS formation is widely unclear. We thus investigated the frequency, composition, and spatial distribution of PDAC-infiltrating B cells in primary resected (PR) versus neoadjuvant-treated patients using a novel multiplex immunohistochemistry panel. The NeoTx group displayed significantly lower frequencies of pan B cells, GC B cells, plasmablasts, and plasma cells, accompanied by a reduced abundance of TLS. This finding was supported by bulk RNA-sequencing analysis of an independent fresh frozen tissue cohort, which revealed that major B cell pathways were downregulated in the NeoTx group. We further observed that plasma cells frequently formed aggregates that localized close to TLS and that TLS+ patients displayed significantly higher plasma cell frequencies compared to TLS- patients in the PR group. Additionally, high densities of CD20+ intratumoral B cells were significantly associated with longer overall survival in the PR group. While CD20+ B cells held no prognostic value for NeoTx patients, an increased frequency of proliferating CD20+Ki67+ B cells emerged as an independent prognostic factor for longer survival in the NeoTx group. These results indicate that NeoTx differentially affects PDAC-infiltrating immune cells and may have detrimental effects on the existing B cell landscape and the formation of TLS. Gaining further insight into the underlying molecular mechanisms is crucial to overcome the intrinsic immunotherapy resistance of PDAC and develop novel strategies to improve the long-term outcome of PDAC patients.

Pretransplant use of immune checkpoint inhibitors for hepatocellular carcinoma: A multicenter, retrospective cohort study

Immune checkpoint inhibitors (ICIs) as a downstaging or bridging therapy for liver transplantation (LT) in hepatocellular carcinoma patients are rapidly increasing. However, the evidence about the feasibility and safety of pre-LT ICI therapy is limited and controversial. To this end, a multicenter, retrospective cohort study was conducted in 11 Chinese centers. The results showed that 83 recipients received pre-LT ICI therapy during the study period. The median post-LT follow-up was 8.1 (interquartile range 3.3-14.6) months. During the short follow-up, 23 (27.7%) recipients developed allograft rejection, and 7 of them (30.4%) were diagnosed by liver biopsy. Multivariate logistics regression analysis showed that the time interval between the last administration of ICI therapy and LT (TLAT) ≥ 30 days was an independent protective factor for allograft rejection (odds ratio = 0.096, 95% confidence interval 0.026-0.357; P < .001). Multivariate Cox analysis showed that allograft rejection was an independent risk factor for overall survival (hazard ratio = 9.960, 95% confidence interval 1.006-98.610; P = .043). We conclude that patients who receive a pre-LT ICI therapy with a TLAT shorter than 30 days have a much higher risk of allograft rejection than those with a TLAT longer than 30 days. The presence of rejection episodes might be associated with higher post-LT mortality.

Identification and validation of a novel anoikis-related prognostic model for prostate cancer.

Anoikis resistance is a hallmark characteristic of oncogenic transformation, which is crucial for tumor progression and metastasis. The aim of this study was to identify and validate a novel anoikis-related prognostic model for prostate cancer (PCa). We collected a gene expression profile, single nucleotide polymorphism mutation and copy number variation (CNV) data of 495 PCa patients from the TCGA database and 140 PCa samples from the MSKCC dataset. We extracted 434 anoikis-related genes and unsupervised consensus cluster analysis was used to identify molecular subtypes. The immune infiltration, molecular function, and genome alteration of subtypes were evaluated. A risk signature was developed using Cox regression analysis and validated with the MSKCC dataset. We also identify potential drugs for high-risk group patients. Two subtypes were identified. C1 exhibited a higher level of CNV amplification, immune score, stromal score, aneuploidy score, homologous recombination deficiency, intratumor heterogeneity, single-nucleotide variant neoantigens, and tumor mutational burden compared to C2. C2 showed a better survival outcome and had a high level of gamma delta T cell and activated B cell infiltration. The risk signature consisting of four genes (HELLS, ZWINT, ABCC5, and TPSB2) was developed (area under the curve = 0.780) and was found to be an independent prognostic factor for overall survival in PCa patients. Four CTRP-derived and four PRISM-derived compounds were identified for high-risk patients. The anoikis-related prognostic model developed in this study could be a useful tool for clinical decision-making. This study may provide a new perspective for the treatment of anoikis-related PCa.

Clinical outcome of non-curative endoscopic submucosal dissection for early gastric cancer.

Early gastric cancer (EGC) is defined as cancer cells confined to the mucosal or submucosal layer, irrespective of size or presence of lymph node metastasis. The recent EGC endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) guidelines (2021 Japan Gastroenterological Endoscopy Society (JGES) guidelines, 2nd edition) revised the concept from "endoscopic curative/non-curative resection" (NCR) to "endoscopic curability (eCura)". Under this, eCuraA and eCuraB signify curative resections (CRs), while eCuraC (including eCuraC-1 and eCura-C2) indicate NCRs. This study retrospectively analyzes clinical and pathological data from EGC patients who underwent endoscopic resection, assessing the long-term clinical outcomes in a substantial cohort after undergoing NCR. We retrospectively analyzed clinical and pathological data from 443 EGC patients, encompassing 478 lesions, who received endoscopic treatment. The long-term clinical outcomes of patients who underwent NCR were statistically evaluated. Characteristics of the NCR group were compared with those of the surgical group, employing single- and multi-factor logistic regression analyses to identify risk factors that necessitate further surgical intervention. Prognostically, the Kaplan-Meier method and Log-Rank test determined the impact of risk factors on recurrence-free survival post-surgery in NCR patients. Differences were assessed using a method incorporating statistically significant differences in the multi-factor Cox regression analysis, evaluating the hazard ratio (HR) for disease recurrence following NCR. In this study, 443 EGC cases were pathologically diagnosed, comprising a total of 478 lesions. Of these, 127 cases underwent non-curative endoscopic resection, resulting in a NCR rate of 24.4%. Long-term follow-up was achieved for 117 (92.12%) patients. The metastasis/recurrence rate at 6 months stood at 23.1%. Multivariate Cox regression analysis identified lesion size ≥2.0 and <3 cm [P=0.02, HR =0.12, 95% confidence interval (CI): 0.02-0.67], presence of ulceration (P=0.03, HR =5.48, 95% CI: 1.23-24.33), lymphatic invasion (P=0.05, HR =17.51, 95% CI: 1.07-286.23), positive vertical margins (P=0.09, HR =3.77, 95% CI: 0.81-17.53), and flat macroscopic morphology (P=0.048, HR =4.8, 95% CI: 1.01-22.73) as independent risk factors for recurrence-free survival post non-curative endoscopic resection in EGC patients. The recurrence/metastasis rate in patients who underwent NCR is notably higher compared to the control group. Significant prognostic risk factors include tumor size ≥2.0 and <3 cm, positive vertical margins, lymphatic invasion, and flat type (one of pathological gross classification). Patients in the eCuraC-2 category of NCR should consider further surgical intervention. The necessity for additional surgical intervention in these patients warrants further investigation.

Development and Validation of a Nomogram for Patients Undergoing Transarterial Chemoembolization for Recurrent Hepatocellular Carcinoma After Hepatectomy.

This study aims to establish a prognostic nomogram for patients who underwent transarterial chemoembolization (TACE) for recurrent hepatocellular carcinoma (HCC) after hepatectomy. Patients who underwent TACE for recurrent early- and middle-stage HCC after hepatectomy between 2009.01 and 2015.12 were included. Enrolled patients were randomly divided into training (n=345) and validation (n=173) cohorts according to a computer-generated randomized number. Independent factors for overall survival (OS) were determined and included in the nomogram based on the univariate and multivariate analyses of the training group. The nomogram was validated and compared to other prognostic models. Discriminative ability and predictive accuracy were determined using the Harrell C index (C-index), area under the receiver operating characteristic curve (AUROC), and calibration curve. The final nomogram was established based on four parameters including resection-to-TACE time interval, recurrent tumor diameter, recurrent tumor number, and AFP level. The C-indexes of the nomogram for predicting OS were 0.67 (95% CI 0.63-0.70) and 0.71 (95% CI 0.68-0.74) in the training and validation cohort respectively. The AUROCs for predicting the 1-year, 2-year and 3-year OS based on the nomogram were also superior to those of the other models. The calibration curve for 3-year survival showed a high congruence between the predicted and actual survival probabilities. According to the scores calculated by the nomogram, patients were stratified into three subgroups: high-risk (scoring ≥53 points), middle-risk (scoring ≥26 and <53 points), and low-risk (scoring <26 points) subgroups with a median OS of 10.1 (95% CI 0.63-0.70), 20.3 (95% CI 17.5-22.5) and 47.0 (95% CI 34.2-59.8) months, respectively. The proposed nomogram served as a new tool to predict individual survival in patients who underwent TACE for recurrent HCC after hepatectomy, with favorable performance and discrimination. For high-risk patients, treatment should be optimized beyond TACE alone based on the nomogram.

Focal-to-bilateral tonic-clonic seizures and High-grade CMV-infection are poor survival predictors in Tumor-related Epilepsy Adult-type diffuse gliomas—A single-center study and literature review

IntroductionPrevious studies have reported a correlation between a high-grade CMV-infection and an unfavorable prognosis in glioblastoma (GB). Coversely, epilepsy has been associated with a more favorable outcome in GB patients. Despites epilepsy and CMV share similar molecular mechanisms in GB tumoral microenvironment, the correlation between Tumor-Related-Epilepsy (TRE) and CMVinfection remains unexplored. The aim of our study is to examine the correlation between the dregree of CMV infection and seizure types on the survival of TRE Adult-type-diffuse-glioma. To achieve this objective, we conducted a comprehensive literature review to assess our results regarding previous publications MethodsWe conducted a retrospective-observational study on TRE Adult-type-diffuse-gliomas treated at a single center in Mexico from 2010 to 2018. Tumor tissue and cDNA were analyzed by immunochemistry (IHC) for CMV (IE and LA antigens) at the Karolinska Institute in Sweden, and RT-PCR for CMV-gB in Torreon Mexico, respectively. Bivariate analysis (X2-test) was performed to evaluate the association between subtypes of Adult-type-diffuse-glioma (IDH-mut grade 4 astrocytoma vs. IDH-wt glioblastoma) and the following variables: type of hemispheric involvement (mesial vs. neocortical involvement), degree of CMV infection (<25%vs. >25% infected-tumoral cells) and seizure types [Focal awareness, focal impaired awareness, and FBTCS]. Kaplan Meier and Cox analyses were performed to determine the risk, p < 0.05 was considered statistically significant. ResultsSixty patients with TRE Adult type diffuse gliomas were included (80% IDH-wt glioblastoma and 20% IDH-mut grade 4astrocytomas). The mean age was 61.5 SD ± 18.4, and 57% were male. Fifty percent of the patients presented with mesial involvement of the hemysphere. Seizure types included focal awareness (15%), focal impaired awareness (43.3%), and FBTCS (41.7%). Ninety percent of cases were treated with Levetiracetam and 33.3% presented Engel-IA postoperative seizure control. More than 90% of samples were positive for CMV-immunohistochemistry (IHC). However, all cDNA analyzed by RT-PCR return negative results. The median of overall survival (OS) was 15 months. High-grade CMV-IE infection (14 vs. 25 months, p<0.001), mesial involvement (12 vs. 18 months, p<0.001), and FBTCS were associated with worse OS (9 vs.18 months for non-FBTCS). Multivariate analysis demonstrated that high-grade CMV infection (HR = 3.689, p=0.002) and FBTCS (HR=7.007, p<0.001) were independent unfavorable survival factors. ConclusionsCMV induces a proinflammatory tumoral microenvironment that contributes to the developmet of epilepsy. Tumor progression could be associated not only with a higher degree of CMV infection but also to epileptogenesis, resulting in a seizure phenotype chracterized by FBTCS and poor survival outcomes. This study represents the first survival analysis in Latin America to include a representative sample of TRE Adult-type diffuse gliomas considering CMV-infection-degree and distinguishing features (such as FBTCS) that might have potential clinical relevance in this group of patients. Further prospective studies are required to validate these results.

The Association between the rs3747406 Polymorphism in the Glucocorticoid-Induced Leucine Zipper Gene and Sepsis Survivals Depends on the SOFA Score.

The variability in mortality in sepsis could be a consequence of genetic variability. The glucocorticoid system and the intermediate TSC22D3 gene product-glucocorticoid-induced leucine zipper-are clinically relevant in sepsis, which is why this study aimed to clarify whether TSC22D3 gene polymorphisms contribute to the variance in sepsis mortality. Blood samples for DNA extraction were obtained from 455 patients with a sepsis diagnosis according to the Sepsis-III criteria and from 73 control subjects. A SNP TaqMan assay was used to detect single-nucleotide polymorphisms (SNPs) in the TSC22D3 gene. Statistical and graphical analyses were performed using the SPSS Statistics and GraphPad Prism software. C-allele carriers of rs3747406 have a 2.07-fold higher mortality rate when the sequential organ failure assessment (SOFA) score is higher than eight. In a multivariate COX regression model, the SNP rs3747406 with a SOFA score ≥ 8 was found to be an independent risk factor for 30-day survival in sepsis. The HR was calculated to be 2.12, with a p-value of 0.011. The wild-type allele was present in four out of six SNPs in our cohort. The promoter of TSC22D3 was found to be highly conserved. However, we discovered that the C-allele of rs3747406 poses a risk for sepsis mortality for SOFA Scores higher than 6.

Treatment of local recurrence of esophageal cancer following Ivor-Lewis esophagectomy-Experiences of a high-volume center.

Patients with local recurrence of esophageal cancer have a highly decreased overall survival. There is currently no standardized treatment algorithm for this group. This retrospective cohort study aimed to evaluate the survival of patients with local recurrence, despite receiving individualized treatment options. 241 of 1791 patients were diagnosed with a local recurrence following Ivor-Lewis esophagectomy at the University Hospital of Cologne. 59 patients, who were diagnosed only with a local recurrence of adeno- or squamous cell carcinoma and received their individualized therapy regimes at our high-volume center, were included. The study included 52 patients with adenocarcinoma and 7 with squamous cell carcinoma. Among these, 6 patients underwent resection, 19 received solely chemotherapy, 29 received chemoradiotherapy, and 5 were provided with best supportive care. Patients who underwent resection showed a better survival outcome compared to patients without resection (median OS: not reached vs. 15.1months, p=0.012). Best supportive care and palliative care were found to be independent risk factors for shorter overall survival compared to curative intended treatment options like local resection or chemoradiotherapy. In this study, different treatment strategies for patients with local recurrence of esophageal cancer were depicted. Resection as well as chemoradiotherapy could play a role in selected patients. Further prospective studies are needed to improve the selection of eligible patients.

The CRP-albumin-lymphocyte (CALLY) Index Is an Independent Prognostic Factor for Gastric Cancer Patients who Receive Curative Treatment.

The CRP-albumin-lymphocyte (CALLY) index is a promising biomarker. We clarified the clinical impact of the CALLY index in gastric cancer patients who received curative treatment. Consecutive patients who underwent curative resection for gastric cancer at Yokohama City University from 2005 to 2020 were selected based on medical records. The CALYY index was calculated as follows: serum ALB level (g/dl) × lymphocyte count (cells/μl)/C-reactive protein (mg/dl) ×104 Results: Two hundred fifty-nine patients were included in the present study. The three- and five-year overall survival (OS) rates were 64.8% and 57.0%, respectively, in the CALLY index-low group, and 86.2% and 78.2%, respectively, in the CALLY index-high group. There were significant differences between the two groups. A multivariate analysis demonstrated that the CALLY index was an independent prognostic factor for overall survival (hazard ratio=1.791; 95% confidence interval=1.067-3.009; p=0.028). When comparing the perioperative clinical course between the CALLY index-low and CALLY index-high groups, there were significant differences in postoperative surgical complications and adjuvant chemotherapy. The CALLY score was an independent prognostic factor for patients with gastric cancer. Our results suggest that the CALLY index is a promising tool for assessing inflammation and nutritional status in patients undergoing gastric cancer treatment and management.

Prediction of tumor recurrence after surgical resection of ampullary adenocarcinoma using magnetic resonance imaging.

To predict tumor recurrence in patients who underwent surgical resection of ampullary adenocarcinoma using preoperative magnetic resonance (MR) imaging findings combined with clinical findings. In this multicenter study, a total of 113 patients (mean age, 62.9 ± 9.8 years; 58 men and 55 women) with ampullary adenocarcinoma who underwent preoperative MR imaging and surgery with margin-negative resection between 2006 and 2017 were retrospectively included. The MR imaging findings were evaluated by two radiologists. Preoperative clinical findings were obtained. Cox proportional regression analyses were used to identify the independent prognostic factors for recurrence-free survival (RFS). A nomogram was created based on the multivariable analysis and was internally validated. Multivariable analysis revealed that presence of infiltrative tumor margin (hazard ratio [HR]: 2.18, p = 0.019), adjacent organ invasion (HR: 3.31, p = 0.006), adjacent vessel invasion (HR: 5.42, p = 0.041), peripancreatic lymph node enlargement (HR: 2.1, p = 0.019), and jaundice (HR: 1.93, p = 0.043) were significantly associated with worse RFS of ampullary adenocarcinoma after surgical resection. These MR imaging and clinical findings were used to construct a nomogram. On internal validation, the calibration plots showed excellent agreement between the predicted probabilities and the actual rates of tumor recurrence, with Harrell's c-index of 0.746. Combination of preoperative MR imaging and clinical findings can be useful for predicting tumor recurrence after surgical resection of ampullary adenocarcinoma. Identifying these features before surgery may aid in better treatment planning and management of these patients. A predictive nomogram using preoperative MR imaging and clinical findings can be useful in estimating the recurrence-free survival after surgical resection of ampullary adenocarcinoma. • Presently, tumor size on imaging is the only non-invasive factor that correlates with recurrence-free survival from ampullary adenocarcinoma; other factors are obtained postoperatively. • Infiltrative tumor margin, adjacent organ invasion, adjacent vessel invasion, peripancreatic lymph node enlargement on MRI, and jaundice are significant predictors for recurrence. • A nomogram incorporating significant MR imaging and clinical findings showed good performance in predicting recurrence-free survival, which can help in treatment planning.

Prognostic significance of antifibrotic agents in idiopathic pulmonary fibrosis after initiation of long-term oxygen therapy.

Idiopathic pulmonary fibrosis (IPF) is a fatal and progressive interstitial lung disease with varying degrees of hypoxemia. Long-term oxygen therapy (LTOT) is frequently used to treat hypoxemia, however the prognostic factors for better survival in IPF patients after initiation of LTOT remain unknown. We retrospectively investigated favorable factors of survival in consecutive 55 IPF patients with chronic respiratory failure who were introduced LTOT. The 6-, 12-, 18-, and 24-month survival rates in IPF patients after introduction of LTOT were 70.9%, 49.0%, 45.2%, and 32.3%, respectively. Univariate analysis demonstrated that low Glasgow Prognostic Score (GPS) (hazard ratio [HR] 0.482, p=0.043) and treatment with antifibrotic agents (HR 0.401, p=0.013) were associated with favorable survival, while multivariate analysis revealed that treatment with antifibrotic agents was the independent predictor (HR 0.449, p=0.032). Moreover, IPF patients treated with antifibrotic agents with LTOT had significantly longer survival than those without antifibrotic agents (p = 0.0106). In IPF patients who were introduced LTOT, treatment with antifibrotic agents was the independent factor for favorable survival. Treatment with antifibrotic agents may improve prognosis of IPF even after initiation of LTOT.

Enhanced epithelial-mesenchymal transition signatures are linked with adverse tumor microenvironment, angiogenesis and worse survival in gastric cancer.

Epithelial-mesenchymal transition (EMT) is a crucial mechanism that facilitates cancer cell metastasis. Despite its importance, the clinical significance of EMT in gastric cancer (GC) patients has yet to be clearly demonstrated. For gauging the extent of EMT in GC, we employed gene set variation analysis to score 807 patient samples from two large cohorts: TCGA and GSE84437. In both cohorts, EMT high GC showed a significant association with worse overall survival (hazard ratio (HR) = 1.74, p = 0.011 and HR = 2.01, p < 0.001, respectively). This association was stronger when considering the EMT signature score compared to the individual expressions of EMT-related genes (CDH1, CDH2, VIM, and FN1). While the EMT signature level did not differ among various cancers, high EMT signature specifically correlated with survival in GC alone. Mucinous and diffuse histological types exhibited higher EMT levels compared to others (p < 0.001), and the EMT signature level was correlated with tumor depth and AJCC stage (all p < 0.001). Interestingly, the EMT score was an independent factor for overall and disease-specific survival (multivariate; p = 0.006 and 0.032, respectively). EMT high GC displayed a lower fraction of Th1 cells and a higher fraction of dendritic cells, M1 macrophages and several stromal cells. EMT high GC exhibited an inverse correlation with cell proliferation-related gene sets. While they significantly enriched multiple pro-cancerous gene sets, such as TGF-β signaling, hypoxia, and angiogenesis. The presence of EMT signature in a bulk tumor was linked to TGF-β signaling, hypoxia, and angiogenesis, and was also associated with poorer survival outcomes in GC patients.

Abstract 1053: The Influence of PD1 and TIM3 Expression on CD4+CD103+ and CD8+CD103+ Cells in Glioblastoma Progression

Abstract Glioblastoma (GB), IDH-wildtype, is the most common and aggressive high-grade primary malignant brain tumor with extremely poor outcome. Although the use of immune checkpoint inhibitors (ICIs) in GB has shown disappointing results, the identification of a small subgroup of responders underpins the role of the intratumoral immune contexture, in particular tumour-infiltrating lymphocytes (TILs), in determining disease outcome. This study aims to define the features of TIL subpopulations correlating with GB prognosis, and to establish in parallel the predictive roles of peripheral T cell subsets. A single cohort observational study, including patients undergoing GB resection and standard therapeutic and follow-up approaches in Neuro-Oncology, was conducted. Of the 45 patients, histologically confirmed WHO grade 4, 26 had MGMT promoter methylation (60.0%), 24 were male (53.3%) and the median age of young patients (≤63 years) vs elderly patients (&amp;gt;63 years) was 57 vs 71, respectively. Predictors of OS were KPS (≥70 vs &amp;lt;70: 14.7 vs 7.5 months, p=0.0007) and GTR (GTR vs non-GRT: 15 vs 9 months, p=0.004) whereas patients with methylated MGMT promoter had non-significant longer median OS compared to those with unmethylated promoter (14.5 vs 10.5 months). Patients were characterized for the expression of lineage, differentiation, memory, activation, and inhibition markers on intratumoral and peripheral CD4+ and CD8+ T cell subpopulations, and the correlation of an array of CD4+ and CD8+ T cell subsets with OS or PFS was evaluated by multiparametric flow cytometry and uni/multivariate analyses. Intratumoral immune infiltrate was positively associated with CD8+CD103+ tissue-resident memory T cells (Trm), and in particular with CD8+CD103+ Trm expressing PD1 and TIM3 rather than CD4+ Trm. Low CD8+CD103+PD1+ Trm resulted significantly associated with better OS and PFS (p=0.02 and 0.0031, respectively) and even higher significant was the correlation with better OS and PFS of low CD8+CD103+TIM3+ Trm (p=0.0002 and 0.0033, respectively) and CD8+CD103+PD1+TIM3+ Trm (p&amp;lt;0.0001, both). On multivariate analysis, low CD8+CD103+PD1+TIM3+ Trm and KPS ≥70 were confirmed to be the most predictive independent factors associated with longer OS (hazard ratios - HR [95%CI]: 0.14 [0.04 - 0.52] p˂0.001, 0.39 [0.16 - 0.96] p=0.04, respectively). Moreover, CD8+CD103+ Trm subpopulations resulted age-related predictors for GB survival. Consistent with this finding, in vitro PD1 and TIM3 blockade released the capability of intratumoral T cells to produce the effector cytokines IFN-γ and TNF-α, and the cytotoxic factor GrzB. Conversely, T cells expressing PD1 and TIM3 of peripheral blood did not show any prognostic significance. In conclusion, low frequency of Trm expressing PD1 or TIM3 or both markers defined TIL subsets as independent positive prognostic factors for patient survival. Citation Format: Lucia Gabriele, Giulia Romagnoli, Quintino Giorgio D'Alessandris, Imerio Capone, Andrea Tavilla, Irene Canini, Caterina Lapenta, Mariachiara Buccarelli, Martina Giordano, Valentina Tirelli, Massimo Sanchez, Alessandra Fragale, Stefano Giannetti, Rina Di Bonaventura, Liverana Lauretti, Mauro Biffoni, Lucia Ricci-Vitiani, Roberto Pallini. The Influence of PD1 and TIM3 Expression on CD4+CD103+ and CD8+CD103+ Cells in Glioblastoma Progression [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 1053.