Survival Value Research Articles

Decision-Tree Models Indicative of Microvascular Invasion on MRI Predict Survival in Patients with Hepatocellular Carcinoma Following Tumor Ablation.

Histological microvascular invasion (MVI) is a risk factor for poor survival and early recurrence in hepatocellular carcinoma (HCC) after surgery. Its prognostic value in the setting of locoregional therapies (LRT), where no tissue samples are obtained, remains unknown. This study aims to establish CT-derived indices indicative of MVI on liver MRI with superior soft tissue contrast and evaluate their association with patient survival after ablation via interstitial brachytherapy (iBT) versus iBT combined with prior conventional transarterial chemoembolization (cTACE). Ninety-five consecutive patients, who underwent ablation via iBT alone (n = 47) or combined with cTACE (n = 48), were retrospectively included between 01/2016 and 12/2017. All patients received contrast-enhanced MRI prior to LRT. Overall (OS), progression-free survival (PFS), and time-to-progression (TTP) were assessed. Decision-tree models to determine Radiogenomic Venous Invasion (RVI) and Two-Trait Predictor of Venous Invasion (TTPVI) on baseline MRI were established, validated on an external test set (TCGA-LIHC), and applied in the study cohorts to investigate their prognostic value for patient survival. Statistics included Fisher's exact and t-test, Kaplan-Meier and cox-regression analysis, area under the receiver operating characteristic curve (AUC-ROC) and Pearson's correlation. OS, PFS, and TTP were similar in both treatment groups. In the external dataset, RVI showed low sensitivity but relatively high specificity (AUC-ROC = 0.53), and TTPVI high sensitivity but only low specificity (AUC-ROC = 0.61) for histological MVI. In patients following iBT alone, positive RVI and TTPVI traits were associated with poorer OS (RVI: p < 0.01; TTPVI: p = 0.08), PFS (p = 0.04; p = 0.04), and TTP (p = 0.14; p = 0.03), respectively. However, when patients with combined cTACE and iBT were stratified by RVI or TTPVI, no differences in OS (p = 0.75; p = 0.55), PFS (p = 0.70; p = 0.43), or TTP (p = 0.33; p = 0.27) were observed. The study underscores the role of non-invasive imaging biomarkers indicative of MVI to identify patients, who would potentially benefit from embolotherapy via cTACE prior to ablation rather than ablation alone.

Adaptación de leguminosas arbóreas en un sistema silvopastoril para ovinos en clima templado

The objective was to evaluate, over a one-year period, the survival, production, and nutritional value of forage from tree legumes as well as grasses and weeds in a silvopastoral system. A mixed protein bank was established, consisting of two plots: in the first plot, planting orientation was East to West, and in the second, North to South. The planted tree species were leguminous: pata de vaca (Bauhinia forficata), albizia (Albizia lebbeck), leucaena (Leucaena leucocephala), and palo dulce (Eysenhardtia polystachya). Three planting densities were used, with tree spacings of 70x70, 90x90, and 110x110 cm. Survival was assessed visually and manually by identifying the species and recording their condition as either alive (1) or dead (0). A three-way classification model with an unequal number of repetitions was used, employing the Generalized Linear Models procedure of the statistical analysis system under a fixed effects model. The nutritional value of thetree legumes ranged from 11% to 18% protein. Differences (p ≤ 0.05) were observed between treatments and orientation regarding height. There was a significant effect (p ≤ 0.05) of treatment, orientation, period, and species on foliage production. Differences (p ≤ 0.05) were found in species survival, with albizia (Albizia lebbeck) being notable. The period also significantly influenced (p ≤ 0.05) tree survival. It is concluded that the survival rate of forage tree legume species determines their capacity to establish silvopastoral systems in a subhumid temperate climate in mixed protein bank arrangements

Predicting the response of a long-distance migrant to changing environmental conditions in winter.

Access to high-quality food is critical for long-distance migrants to provide energy for migration and arrival at breeding grounds in good condition. We studied effects of changing abundance and availability of a marine food, common eelgrass (Zostera marina L.), on an arctic-breeding, migratory goose, black brant (Brant bernicla nigricans Lawrence 1846), at a key non-breeding site, Bahía San Quintín, Mexico. Eelgrass, the primary food of brant, is consumed when exposed by the tide or within reach from the water's surface. Using an individual-based model, we predicted effects of observed changes (1991-2013) in parameters influencing food abundance and availability: eelgrass biomass (abundance), eelgrass shoot length (availability, as longer shoots more within reach), brant population size (availability, as competition greater with more birds), and sea level (availability, as less food within reach when sea level higher). The model predicted that the ability to gain enough energy to migrate was most strongly influenced by eelgrass biomass (threshold January biomass for migration = 60 g m-2 dry mass). Conversely, annual variation in population size (except for 1998), was relatively low, and variation in eelgrass shoot length and sea level were not strongly related to ability to migrate. We used observed data on brant body mass at Bahía San Quintín and annual survival to test for effects of eelgrass biomass in the real system. The lowest observed values of body mass and survival were in years when biomass was below 60 g m-2, although in some years of low biomass body mass and/or survival was higher. This suggests that the real birds may have some capacity to compensate to meet their energy demands when eelgrass biomass is low. We discuss consequences for brant population trends and conservation.

Prognostic Value of Serum Galectin-3 for Survival in Patients with Cardiac Light-Chain Amyloidosis.

Amyloid light-chain (AL) amyloidosis is a multisystem disorder, with cardiac amyloid infiltration being a prevalent manifestation. This study aimed to explore the prognostic value of galectin-3 (Gal-3), a soluble marker associated with fibrosis, inflammation, heart failure, and kidney injury, in patients with cardiac AL amyloidosis. A total of 60 patients who were diagnosed with cardiac AL amyloidosis from January 2015 to May 2018 were enrolled. The prognostic value of Gal-3 was assessed. Receiver operating characteristic (ROC) curves were used to evaluate the predictive accuracy of Gal-3. A Gal-3 cut-off value was identified to predict survival rates. The ROC curves demonstrated a moderate predictive accuracy of Gal-3 for 0.5- and 5-year survival, with area under the curve (AUC) values of 0.722 and 0.788, respectively. A Gal-3 cut-off value of 15.154 ng/mL was found to predict survival. Kaplan-Meier survival analysis revealed a significant difference in mean overall survival between patients with Gal-3 levels below and above the established cut-off (69.2 months versus 42.1 months, respectively; p = 0.036). Multivariate analysis confirmed that Gal-3 > 15.154 ng/mL remained an independent predictor of survival (HR 2.451, 95% CI 1.017-5.910, p = 0.046). This study suggests that Gal-3 holds independent prognostic value for survival in patients with cardiac AL amyloidosis. Gal-3 could potentially enhance the prognostic capabilities of the current soluble markers, thereby improving the management of cardiac AL amyloidosis. However, further validation in larger prospective studies is warranted.

Long-term survival of cancer patients after photobiomodulation therapy for prevention and treatment of oral mucositis

BackgroundPhotobiomodulation therapy (PBMT) has been employed for the prevention and treatment of oral mucositis in patients with head and neck cancer undergoing treatment. However, information about the survival of patients receiving PBMT is still lacking. Therefore, the aim of this study was to correlate the survival of patients who either received or did not receive PBMT, combined with cancer treatments, and to assess whether the number of PBMT sessions had a positive impact on survival. MethodsThe records of 751 patients seen at Hospital de Caridade São Vicente de Paulo diagnosed with head and neck cancer, treated by D.L.P., the sole operator of PBMT, between 2000 and 2016, were analyzed. The median survival rates were compared by analyzing diagnostic staging, the combination of cancer treatments, and the number of PBMT sessions. Correlation analyses were performed to assess the interactions between the number of PBMT sessions and survival. ResultsPBMT increased survival by 55.14 %, from 1.07 (Without PBMT) to 1.66 years (With PBMT) for the total population and more significantly in Group 41 (stages III and IV, radiation therapy/chemotherapy, with more than five PBMT sessions), the median survival value of 1.83 years, which represents a 66.36 % higher survival rate. In all the analyzed populations, the larger number of sessions was associated with better survival. In terms of survival, advanced stages III and IV almost equated with stages I and II in the absence of PBMT. ConclusionsPBMT seems to interfere with the survival of patients with head and neck cancer, corroborating its recommendation for the treatment of mucositis, but further research is needed to investigate possible synergistic effects between PBMT and cancer treatments.

Reproductive conditioning, spawning induction and early development of the estuarine Caribbean clam, Polymesoda arctata (Deshayes, 1854), under hatchery conditions

Polymesoda arctata is a Caribbean estuarine clam commercially important that currently is considered threatened. The reproductive conditioning, spawning and early development were evaluated under laboratory conditions using organisms collected in the lagoon system of Ciénaga Grande de Santa Marta (Colombian Caribbean) between December 2020 and May 2021. Two reproductive conditioning experiments were conducted over 7 weeks, examining the frequency of mature animals in the natural environment (controls) and in the laboratory under two water temperatures (26 and 29 °C) and different salinity regimes (constant at 5 and 15 ppt, increasing from 5 to 15 ppt, and decreasing from 15 to 5 ppt). One spawning experiment was done, comparing the spawning response of adult clams exposed to various stimuli (changes in water temperature and salinity, flow of seawater irradiated with UV light, addition of a high concentration of food and sperm to the water, as well as injections of serotonin and KCl into the foot and/or adductor muscle). Higher frequencies of mature clams were observed after 2 to 5 weeks of reproductive conditioning at a low temperature (26 °C) and under a constant salinity regime (at 5 or 15 ppt). Higher percentages of spawning and post-stimulation survival as well as spawning response speed were observed in specimens injected in the foot with a low concentration of serotonin (0.4 mL at 20 μM). The time of spawning response onset was shorter in males than in females. The fecundity increased with the live weight of the females, showing an average value of 3.4 × 106 oocytes per female. The early development of the estuarine clam from oocyte to juvenile stage was described in detail. The growth rates of larvae and spat were relatively high but their survival values were low, showing the need for additional research on the larval and post-larval rearing.

Syndecan-1 as a prognostic biomarker in COVID-19 patients: a retrospective study of a Japanese cohort

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact, with millions of confirmed cases and deaths worldwide. While most cases are mild, a subset progresses to severe respiratory complications and death, with factors such as thromboembolism, age, and underlying health conditions increasing the risk. Vascular endothelial damage has been implicated in severe outcomes, but specific biomarkers remain elusive. This study investigated syndecan-1 (SDC-1), a marker of endothelial damage, as a potential prognostic factor for COVID-19, focusing on the Japanese population, which is known for its aging demographics and high prevalence of comorbidities.MethodsA multicenter retrospective study of COVID-19 patients in Fukushima Prefecture in Japan who were admitted between February 2020 and August 2021 was conducted. SDC-1 levels were measured along with other clinical and laboratory parameters. Outcomes including thrombosis, 28-day survival, and disease severity were assessed, and disease severity was categorized according to established guidelines.ResultsSDC-1 levels were correlated with disease severity. Patients who died from COVID-19 had greater SDC-1 levels than survivors, and the area under the receiver operating characteristic curve (AUC) analysis suggested the potential of the SDC-1 level as a predictor of mortality (AUC 0.714). K‒M analysis also revealed a significant difference in survival based on an SDC-1 cutoff of 10.65 ng/mL.DiscussionThis study suggested that SDC-1 may serve as a valuable biomarker for assessing COVID-19 severity and predicting mortality within 28 days of hospitalization, particularly in the Japanese population. However, further investigations are required to assess longitudinal changes in SDC-1 levels, validate its predictive value for long-term survival, and consider its applicability to new viral variants.ConclusionsSDC-1 is emerging as a potential biomarker for assessing the severity and life expectancy of COVID-19 in the Japanese population, offering promise for improved risk stratification and patient management in the ongoing fight against the virus.

Circ_0004771 regulates malignant biological behaviors and has clinical significance in oral squamous cell carcinoma.

The incidence of oral squamous cell carcinoma (OSCC) is increasing, and more effective treatment protocols must rapidly be developed to prevent the death of patients and ensure favorable outcomes. CircRNAs are a unique class of noncoding ribonucleic acid (RNA) molecules unaffected by RNA exonucleases. CircRNAs have more stable expression than linear RNAs and are not readily degraded; therefore, they are the newest focus of RNA research. Here, we analyze the mechanism of hsa_circ_0004771 (circ_0004771) in OSCC to provide a clinical reference. Circ_0004771 expression was measured in peripheral blood, cancerous tissues and adjacent tissues of OSCC patients. Patients were followed up for 3 years. The diagnostic value of circ_0004771 for OSCC occurrence, prognosis, recurrence and survival was analyzed with receiver operating characteristic (ROC) curves. OSCC cells were lentivirally transduced with a circ_0004771-silencing or an empty vector to evaluate alterations in cell growth, invasion, and apoptosis. Apoptosis-related and epithelial-mesenchymal transition (EMT)-related protein expression was quantified. BALB/c nude mice were used for tumorigenesis experiments to evaluate tumor growth in vivo after silencing circ_0004771. Circ_0004771 expression was higher in peripheral blood and cancerous tissue of OSCC patients than in control peripheral blood and paracancerous tissue, respectively, exhibiting excellent predictive value for OSCC occurrence, prognosis, recurrence and survival. Silencing circ_0004771 decreased the growth, invasiveness, and EMT capacity and increased the apoptosis of OCC cells. In mice implanted with OSCC cells transduced with the circ_0004771-silencing lentiviral vector, the tumor growth capacity was obviously decreased. Silencing circ_0004771 inhibits the malignant growth of OSCC.

Fetal hemoglobin induction in azacytidine responders enlightens methylation patterns related to blast clearance in higher-risk MDS and CMML

BackgroundAs new treatment options for patients with higher-risk myelodysplastic syndromes are emerging, identification of prognostic markers for hypomethylating agent (HMA) treatment and understanding mechanisms of their delayed and short-term responses are essential. Early fetal hemoglobin (HbF) induction has been suggested as a prognostic indicator for decitabine-treated patients. Although epigenetic mechanisms are assumed, responding patients’ epigenomes have not been thoroughly examined. We aimed to clarify HbF kinetics and prognostic value for azacytidine treated patients, as well as the epigenetic landscape that might influence HbF re-expression and its clinical relevance.ResultsSerial HbF measurements by high-performance liquid chromatography (n = 20) showed induction of HbF only among responders (p = 0.030). Moreover, HbF increase immediately after the first azacytidine cycle demonstrated prognostic value for progression-free survival (PFS) (p = 0.032, HR = 0.19, CI 0.24–1.63). Changes in methylation patterns were revealed with methylated DNA genome-wide sequencing analysis (n = 7) for FOG-1, RCOR-1, ZBTB7A and genes of the NuRD-complex components. Targeted pyrosequencing methodology (n = 28) revealed a strong inverse correlation between the degree of γ-globin gene (HBG2) promoter methylation and baseline HbF levels (p = 0.003, rs = − 0.663). A potential epigenetic mechanism of HbF re-expression in azacytidine responders was enlightened by targeted methylation analysis, through hypomethylation of site -53 of HBG2 promoter (p = 0.039, rs = − 0.504), which corresponds to MBD2-NuRD binding site, and to hypermethylation of the CpG326 island of ZBTB7A (p = 0.05, rs = 0.482), a known HbF repressor. These changes were associated to blast cell clearance (pHBG2 = 0.011, rs = 0.480/pZBTB7A = 0.026, rs = 0.427) and showed prognostic value for PFS (pZBTB7A = 0.037, HR = 1.14, CI 0.34–3.8).ConclusionsEarly HbF induction is featured as an accessible prognostic indicator for HMA treatment and the proposed potential epigenetic mechanism of HbF re-expression in azacytidine responders includes hypomethylation of the γ-globin gene promoter region and hypermethylation of the CpG326 island of ZBTB7A. The association of these methylation patterns with blast clearance and their prognostic value for PFS paves the way to discuss in-depth azacytidine epigenetic mechanism of action.Graphical abstract

LI-RADS Category Can Be a Post-Surgical Prognostic Factor for Intrahepatic Cholangiocarcinoma in Patients with Liver Cirrhosis or Chronic Hepatitis B

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; The Liver Imaging Reporting and Data System (LI-RADS) categorization has been proposed as a potential prognostic indicator for primary liver neoplasms in patients with liver cirrhosis or chronic hepatitis B. This multicenter study aimed to determine whether LI-RADS categorization can offer additional post-surgical prognostic value for intrahepatic cholangiocarcinoma (ICCA) when used in conjunction with the American Joint Committee on Cancer (AJCC) guidelines. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Patients with high risk for hepatocellular carcinoma, surgically confirmed ICCAs, and available preoperative MRI were enrolled. LI-RADS categorization of ICCAs was performed using MRI features, and multivariate analyses were conducted incorporating LI-RADS category, AJCC staging, and clinicopathologic factors to evaluate their predictive value for postoperative recurrence-free survival (RFS) and overall survival (OS). In patients with early recurrence (&amp;lt;2 years), the percentages of AJCC stage I and LR-M or LR tumor-in-vein (TIV) were calculated, respectively. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Among the 166 ICCAs analyzed, 13.3% (22/166) were classified as LR-4/5, 77.7% (129/166) as LR-M, and 9.0% (15/166) as LR TIV. Classifications according to the 8th AJCC guidelines for patients with available post-surgical pathologic data and follow-up imaging were 40.6% (63/155) stage I tumors, 23.9% (37/155) stage II, and 35.5% (55/155) stage III. Multivariate analysis revealed that LI-RADS category (LR-M or LR-TIV) was a significant factor for predicting both RFS (hazard ratio [HR] = 2.86, &lt;i&gt;p&lt;/i&gt; = 0.02) and OS (HR = 3.18, &lt;i&gt;p&lt;/i&gt; = 0.03). Additionally, AJCC staging (II or III) was a significant factor for RFS (HR = 3.90, &lt;i&gt;p&lt;/i&gt; &amp;lt; 0.001) and OS (HR = 3.29, &lt;i&gt;p&lt;/i&gt; &amp;lt; 0.001), male sex was a significant factor for RFS (HR = 1.89, &lt;i&gt;p&lt;/i&gt; = 0.006) and OS (HR = 2.23, &lt;i&gt;p&lt;/i&gt; = 0.002), and positive resection margin was a significant factor for OS (HR = 1.91, &lt;i&gt;p&lt;/i&gt; = 0.03). Among the 80 patients with early recurrence, 97.5% displayed LR-M or LR-TIV features, while 11.3% were AJCC stage I patients. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; The MRI-based preoperative LI-RADS categorization of ICCA provides additional post-surgical prognostic value beyond the AJCC guidelines, with significant implications for both RFS and OS.

The Efficacy of Whole Blood Resuscitation During Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) to Mitigate Post-occlusion Circulatory Collapse: A Translational Model in Large Swine.

Uncontrolled torso hemorrhage is the primary cause of potentially survivable deaths on the battlefield. Zone 1 Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA), in conjunction with damage control resuscitation, may be an effective management strategy for these patients in the prehospital or austere phase of their care. However, the effect of whole blood (WB) transfusion during REBOA on post-occlusion circulatory collapse is not fully understood. Yorkshire male swine (n = 6 per group, 70-90 kg) underwent a 40% volume-controlled hemorrhage. After a 10-minute hemorrhagic shock period, a REBOA balloon was inflated in Zone 1. Fifteen minutes after inflation, 0, 1, or 3 units (450 mL/unit) of autologous WB was infused through the left jugular vein. Thirty minutes after initial balloon inflation, the balloon was deflated slowly over 3 minutes. Following deflation, normal saline was administered (up to 3,000 mL) and swine were observed for 2 hours. Survival (primary outcome), hemodynamics, and blood gas values were compared among groups. Statistical significance was determined by log-rank test, one-way ANOVA, and repeated measures ANOVA. Survival rates were comparable between groups (P = .345) with 66% of control, 33% of the one-unit animals, and 50% of the 3-unit animals survived until the end of the study. Following WB infusion, both the 1-unit and the 3-unit groups had significantly higher blood pressure (P < .01), pulmonary artery pressure (P < .01), and carotid artery flow (P < .01) compared to the control group. WB transfusion during Zone 1 REBOA was not associated with increased short-term survival in this large animal model of severe hemorrhage. We observed no signal that WB transfusion may mitigate post-occlusion circulatory collapse. However, there was evidence of supra-normal blood pressures during WB transfusion.

Influence of Tank Water Depths on Reproductive Performance of Catfish (Heterobranchus longifilis) Valenciennes, 1840

Aims: To determine the optimum water depth required for catfish spawning in hatcheries. Study Design: Treatments were assigned using complete randomized design. Place and Duration of Study: Fish Farm Complex of the Akwa Ibom State University (AKSU), Nigeria. Methodology: Eighteen (18) similarly-sized H. longifilis broodstock (2.51-2.53 kg, 64 – 66 cm): comprising six broodstock of three males and three females, were held for six months at 0.50 m, 0.75 m and 1.0 m pond water depth. All males were sacrificed for milt extraction without hormonal inducement; with milt from each treatment diluted with normal saline solution. Female broodstock from each treatment were separately induced with ovaprim hormones at a single dosage of 0.5ml/kg body weight of fish and allowed for 16 hours before manual stripping; 3g of egg from each broodstock and mixed with the diluted milt and activated with 100 ml of normal saline. The fertilized eggs were incubated and thereafter assessed for percentage fertilization, hatchability, survival and fry production success. Results: broodstock reproductive parameters significantly increased (P = 0.00) with water depth of broodstock culture tank. Percentage fertilizations were: 49.50±0.78, 68.17±0.93, and 82.50±1.44; respectively. Percentage hatchability of broodstock eggs were: 91.37±1.65 significantly higher for 1.0 m water depth group than 67.79±4.58 from 0.75 m water depth treatment while the least value of hatchability 50.31± 0.78 was recorded for broodstock raised at 0.50 m water depth. The fish group raised at 1.0 m water depth also exhibited highest percentage survival value of 97.02 ± 1.09 and fry production success value of 73.08 ± 0.53 while broodstock raised at 0.50 m water depth indicated the least values: % survival, 8.38 ± 0.48 and fry production success of 2.07 ± 0.07. Conclusion: In times or places of water scarcity, H. longifilis broodstock may be raised at pond water of 0.5 m to 1.0 m. But the water depth that would afford the best breeding and reproductive performance is at 1.0 m depth.

The Effect of Adding Thyroxine Hormone (T4) to Commercial Feed on The Growth Profile of Pompano (Trachinotus blochii, Lacapede)

The purpose of this study was to analyze the effect of adding commercial feed with various concentrations of the hormone thyroxine (T4) on the growth profile of star pomfret (T. Blochii, Lacapede). This research was conducted for 50 days at BPBL Sekotong. The method used is an experimental method with a completely randomized design (CRD) which includes 4 treatment levels and 3 replications. consisting of: P1: control (without thyroxine hormone), P2: thyroxine hormone 1 mg/kg feed, P3: thyroxine hormone 1.5 mg/kg feed, P4: thyroxine hormone 2 mg/kg feed. Parameters measured were absolute weight, absolute length, specific growth rate (SGR), feed efficiency (EP), feed conversion ratio (FCR), survival (SR) and water quality. Data were analyzed using variance (ANNOVA) and continued with Duncan's test. The addition of the concentration of thyroxone hormone (T4) in commercial feed can affect the growth of star pomfret but does not affect the value of feed utilization efficiency (EPP), feed conversion (FCR) and survival (SR). The addition of the concentration of thyroxine hormone (T4) 2 mg/kg in commercial feed is the best treatment in star pomfret culture, because it can provide an absolute weight of 7.69 g, an absolute length of 3.50 cm, and a specific growth rate of 2.28%/day.

New T staging recommendations for recurrent nasopharyngeal carcinoma

ObjectiveThe International Union for Cancer Control/American Joint Committee on Cancer (UICC/AJCC) rT staging is not clinically practical for recurrent nasopharyngeal carcinoma (rNPC). The aim of this study was to establish a new rT staging to guide the treatment of rNPC.MethodsWe conducted a retrospective analysis of 175 patients diagnosed with rNPC between January 2012 and December 2020, using ROC curve analysis to evaluate its effectiveness.ResultsWe analyzed the overall survival (OS) and progression-free survival(PFS) of patients diagnosed with rNPC according to the 8th (UICC/AJCC) rT staging, and found that the overall survival of rT1 and rT2 patients (OS; 29.98% vs. 27.09%, p = 0.8059) and progression-free survival (PFS; 28.48% vs. 26.12%, p = 0.4045) had no significant difference. In rT1 and rT2 patients of this study, overall survival(OS; 30.44% vs. 24.91%, p = 0.0229) and progression-free survival(PFS 29.12% vs. 24.03%, p = 0.0459) had a significant difference. Smoking, family history, and time interval of initial recurrence were independent prognostic factors for OS and PFS.ConclusionThe new rT staging of this study has a better predictive value for survival of rNPC patients than the 8th (UICC/AJCC) rT staging.

Expression and Prognostic Significance of LAG-3, TIGIT, VISTA, and IDO1 in Endometrial Serous Carcinoma

Endometrial serous carcinoma (ESC) is an uncommon, aggressive type of endometrial cancer. While immune checkpoint blockade has emerged as a promising treatment option for endometrial carcinomas, research on the expression of immune checkpoints that could serve as prospective immunotherapy targets in ESC is limited. We examined the prevalence and prognostic value of LAG-3, TIGIT, VISTA, and IDO1 in 94 cases of ESC and correlated their expression with CD8+ and FOXP3+ tumor infiltrating lymphocytes (TIL). We observed a positive correlation between LAG-3, TIGIT and VISTA expressed on immune cells, and between these markers and CD8+ and FOXP3+ TIL density. In Kaplan-Meier survival analysis, tumors with high levels of LAG-3 and TIGIT expression had better progression free survival (PFS) and overall survival (OS) than those with lower levels of expression (LAG-3: PFS, p=0.03, OS, p=0.04; TIGIT: PFS, p=0.01, OS, p=0.009). In multivariate analysis, only high TIGIT expression was of independent prognostic value for better overall survival. VISTA expression in immune or tumor cells, and IDO1 expression in tumor cells, did not show a significant association with survival. Our data indicate that LAG-3, TIGIT, and VISTA immune checkpoints have roles in the microenvironment of ESC, and their expression patterns highlight the complex interactions among the different components of this system. High levels of these markers, together with high CD8+ TIL, suggests the potential immunogenicity of a subset of these tumors. Further studies are needed to elucidate the roles of various immune components in the ESC microenvironment and their association with intrinsic tumor properties.

Deep Learning Analysis for Predicting Tumor Spread through Air Space in Early-Stage Lung Adenocarcinoma Pathology Images.

The presence of spread through air spaces (STASs) in early-stage lung adenocarcinoma is a significant prognostic factor associated with disease recurrence and poor outcomes. Although current STAS detection methods rely on pathological examinations, the advent of artificial intelligence (AI) offers opportunities for automated histopathological image analysis. This study developed a deep learning (DL) model for STAS prediction and investigated the correlation between the prediction results and patient outcomes. To develop the DL-based STAS prediction model, 1053 digital pathology whole-slide images (WSIs) from the competition dataset were enrolled in the training set, and 227 WSIs from the National Taiwan University Hospital were enrolled for external validation. A YOLOv5-based framework comprising preprocessing, candidate detection, false-positive reduction, and patient-based prediction was proposed for STAS prediction. The model achieved an area under the curve (AUC) of 0.83 in predicting STAS presence, with 72% accuracy, 81% sensitivity, and 63% specificity. Additionally, the DL model demonstrated a prognostic value in disease-free survival compared to that of pathological evaluation. These findings suggest that DL-based STAS prediction could serve as an adjunctive screening tool and facilitate clinical decision-making in patients with early-stage lung adenocarcinoma.

The tumor immune microenvironment features and their prognostic value in rectal and sigmoid colon signet-ring cell carcinoma.

3544 Background: Signet-ring cell carcinoma (SRCC) of the rectum and sigmoid colon is a rare and highly malignant challenge in clinical practice. Although high PD-1+CD8+ tumor-infiltrating lymphocyte (TIL) infiltration has been reported as a positive prognostic factor in gastric cancer, pancreatic cancer, etc., its role in colorectal SRCC remains unclear. This study aims to explore the immune landscape of colorectal SRCC and its prognostic implications. Methods: The study included 34 patients with stage II-IV SRCC of the rectum and sigmoid colon. The immune contextures of tumor tissues were characterized using multiplex immunofluorescence assays and compared with a cohort of 57 cases of stage II-IV AC. The ratio density and spatial distribution of CD3+, CD8+, PD-1+, PD-L1+ cells, M1/M2 macrophages, and NK cells were quantitively analyzed in both parenchymal (p) and interstitial (i) regions. Characteristics of immune cell infiltration and their prognostic value for long-term survival were investigated in SRCC cases. Results: Compared to AC, SRCC exhibited significantly higher infiltration of CD8+ and CD3+ iTILs in the interstitial region (P=0.00024; P=0.00321, respectively) and elevated CD8+ pTILs infiltration in tumor parenchyma (P=0.041). Conversely, parenchymal infiltration of TILs co-expressing PD-1 was significantly lower in SRCC than AC (PD-1+CD8+ pTILs: P=0.00035; PD-1+CD3+ pTILs: P=5.0e-05). SRCC showed significantly lower infiltration of M1 macrophages in both parenchyma and interstitium (P=0.0035; P=5.4e-09, respectively), lower interstitial infiltration of M2 macrophages (P=1.5e-05), and a borderline lower parenchymal infiltration of M2 macrophages (P=0.0522), compared to AC. Additionally, patients with high parenchymal or interstitial infiltration of PD-1+CD8+ TILs exhibited significantly longer DFS (P=0.00024; P=0.0041, respectively) and OS (P=0.011; P=0.0044, respectively) than those with low infiltration. Multivariate analysis indicated that the level of PD-1+CD8+ pTILs infiltration is an independent prognostic factor for DFS, being independent of CEA levels and TNM stage (P = 0.018; P = 0.02, respectively). Among patients with normal CEA level or of stage II-III, high level of PD-1+CD8+ pTILs infiltration was still associated with significantly improved DFS (P&lt;0.0001; P=0.00018, respectively) and OS (P=0.00021; P&lt;0.0001, respectively). Conclusions: SRCC of rectum and sigmoid colon exhibits distinct immune profiles compared to conventional AC, characterized by higher infiltration of CD8+ and CD3+ TILs, but lower infiltration of PD-1+CD8+ TILs. The unique immune landscape in SRCC, particularly the level of PD-1+CD8+ TILs infiltration and its positive predictive value for DFS and OS, provides new perspectives for immune-based stratification and therapeutic strategies for this clinically significant cancer subtype.

CRAFITY score benefits hepatocellular carcinoma patients treated with transarterial chemoembolization and lenvatinib

AbstractBackgroundThe CRAFITY score serves as a simple and effective predictive model for individuals diagnosed with hepatocellular carcinoma (HCC) and subjected to treatment with atezolizumab and bevacizumab (Atez/Bev). However, no large sample size studies have reported the application of the CRAFITY score among HCC patients undergoing transarterial chemoembolization (TACE) in conjunction with lenvatinib. This research aims to assess the prognostic role of the CRAFITY score in the context of individuals with HCC receiving TACE in combination with lenvatinib.MethodsThis retrospective analysis encompassed 314 individuals diagnosed with HCC who underwent the combination of TACE and lenvatinib at two medical facilities in China from August 2019 to August 2022 (comprising a training cohort of n = 172 and a validation cohort of n = 142). We investigated the prognostic values of overall survival (OS), progression‐free survival (PFS), disease control rate, and objective response rate in the training cohort based on the CRAFITY scores. Furthermore, the predictive capacity of the model was corroborated through validation using an external cohort.ResultsWe included 174 and 142 patients treated with TACE plus lenvatinib in the training and validation cohorts, correspondingly. PFS and OS differed across all three groups in all training and validation cohorts, based on the CRAFITY score (p &lt; 0.001). In both cohorts, the CRAFITY score effectively predicted tumor response (p &lt; 0.001). Moreover, among the 121 patients who received TACE, lenvatinib, and immunotherapy, the CRAFITY score showed promising predictive efficacy in PFS and OS.ConclusionsThe CRAFITY score, utilizing C‐reactive protein and alpha‐fetoprotein values, emerges as a dependable and pragmatic instrument for forecasting the effectiveness of TACE plus lenvatinib in individuals with unresectable HCC. This scoring system holds the potential to assist oncologists in making informed clinical decisions.

The Trends and Outcomes of Initial Palliative Chemotherapy in Patients with Pancreatic Cancer in Korea Based on National Health Insurance Service Data.

Background/Objectives: The survival rate of patients with pancreatic cancer (PC) has improved gradually since the introduction of FOLFIRINOX (FFX) and gemcitabine + albumin-bound paclitaxel (GnP) regimens. However, the trends and outcomes of initial palliative chemotherapy before and after the advent of these regimens and their contribution to survival rates are not well understood. This study aimed to investigate this in patients with PC in Korea using claims data from the National Health Insurance Service (NHIS). Methods: Patients diagnosed with PC who underwent initial palliative chemotherapy between 2007 and 2019 were identified from the NHIS database. Patient demographics, comorbidities, chemotherapy regimens, and survival rates were analyzed using follow-up data up to 2020. Results: In total, 14,760 patients (mean age, 63.78 ± 10.18 years; men, 59.19%) were enrolled. As initial palliative chemotherapy, 3823 patients (25.90%) received gemcitabine alone; 2779 (18.83%) received gemcitabine + erlotinib; 1948 (13.20%) received FFX; and 1767 (11.97%) received GnP. The median survival values were 15.00 months for FFX; 11.04 months for GnP; 8.40 months for gemcitabine alone; and 8.51 months for gemcitabine + erlotinib. The adjusted hazard ratio (aHR) for GnP vs. FFX was 1.291 (95% CI, 1.206-1.383) in the multivariate Cox regression analysis of mortality. Radiation therapy (aHR, 0.667; 95% CI, 0.612-0.728) and second-line chemotherapy (aHR, 0.639; 95% CI, 0.597-0.684) were significantly associated with improved survival. Conclusions: Our study found that first-line chemotherapy with FFX was associated with significantly longer survival than the other regimens, although caution is needed in interpreting the results.

The Ki67 dilemma: investigating prognostic cut-offs and reproducibility for automated Ki67 scoring in breast cancer

PurposeQuantification of Ki67 in breast cancer is a well-established prognostic and predictive marker, but inter-laboratory variability has hampered its clinical usefulness. This study compares the prognostic value and reproducibility of Ki67 scoring using four automated, digital image analysis (DIA) methods and two manual methods.MethodsThe study cohort consisted of 367 patients diagnosed between 1990 and 2004, with hormone receptor positive, HER2 negative, lymph node negative breast cancer. Manual scoring of Ki67 was performed using predefined criteria. DIA Ki67 scoring was performed using QuPath and Visiopharm® platforms. Reproducibility was assessed by the intraclass correlation coefficient (ICC). ROC curve survival analysis identified optimal cutoff values in addition to recommendations by the International Ki67 Working Group and Norwegian Guidelines. Kaplan–Meier curves, log-rank test and Cox regression analysis assessed the association between Ki67 scoring and distant metastasis (DM) free survival.ResultsThe manual hotspot and global scoring methods showed good agreement when compared to their counterpart DIA methods (ICC > 0.780), and good to excellent agreement between different DIA hotspot scoring platforms (ICC 0.781–0.906). Different Ki67 cutoffs demonstrate significant DM-free survival (p < 0.05). DIA scoring had greater prognostic value for DM-free survival using a 14% cutoff (HR 3.054–4.077) than manual scoring (HR 2.012–2.056). The use of a single cutoff for all scoring methods affected the distribution of prediction outcomes (e.g. false positives and negatives).ConclusionThis study demonstrates that DIA scoring of Ki67 is superior to manual methods, but further study is required to standardize automated, DIA scoring and definition of a clinical cut-off.