Univariate Cox Proportional Hazards Analyses Research Articles

Utility of the Modified and High-Sensitivity Modified Glasgow Prognostic Scores for Hypopharyngeal Squamous Cell Carcinoma.

ObjectiveTo determine whether the modified Glasgow prognostic score (mGPS) and high-sensitivity mGPS (HS-mGPS) could predict outcomes among patients with hypopharyngeal squamous cell carcinoma (HSCC).Study DesignRetrospective cohort study.SettingAffiliated university hospital.MethodsWe reviewed the records of 115 patients with histologically confirmed HSCC between March 2007 and December 2019. Univariate and multivariable Cox proportional hazard analyses were performed for overall survival (OS) and disease-free survival (DFS).ResultsThe 5-year OS rates were 84.0% for the mGPS0 group, 47.8% for the mGPS1 group, and 17.9% for the mGPS2 group (P < .0001), while the 5-year OS rates were 86.7% for the HS-mGPS0 group, 69.0% for the HS-mGPS1 group, and 22.2% for the HS-mGPS2 group (P < .001). The mGPS and HS-mGPS were both associated with OS in the univariate analyses, although only the HS-mGPS was independently associated with OS (hazard ratio, 2.68 [95% CI, 1.19-6.05]; P < .05). The 5-year DFS rates were 75.8% for the mGPS0 group, 53.0% for the mGPS1 group, and 13.8% for the mGPS2 group (P < .001), while the 5-year DFS rates were 79.8% for the HS-mGPS0 group, 56.8% for the HS-mGPS1 group, and 11.6% for the HS-mGPS2 group (P < .001). The mGPS and HS-mGPS were both associated with DFS in the univariate analyses, although only the HS-mGPS was independently associated with DFS (hazard ratio, 2.35 [95% CI, 1.03-5.37]; P < .05).ConclusionOur study suggests that the HS-mGPS is useful as prognostic factor in HSCC.

Preoperative transferrin level is a novel indicator of short- and long-term outcomes after esophageal cancer surgery

This study aimed to examine whether preoperative serum transferrin, a rapid-turnover protein, correlates with short- and long-term outcomes after esophagectomy. Preoperative transferrin levels, calculated by summing serum iron and unsaturated iron-binding capacity, were evaluated in 224 patients who underwent esophagectomy for stage I-III esophageal cancer without preoperative treatment. Transferrin levels are directly proportional to total iron-binding capacity (TIBC), and we defined TIBC < 250μg/dL as low transferrin. We evaluated the relationship between preoperative transferrin levels and short- and long-term outcomes after esophagectomy using univariate and multivariate Cox proportional hazards analyses. Of all patients, 25 (11.2%) had low preoperative transferrin levels. Low preoperative transferrin levels were strongly correlated with worse preoperative performance status, advanced pathological T stage, and more open esophagectomy (p = 0.0078, 0.0001, and 0.013, respectively). Patients with low preoperative transferrin levels experienced significantly more frequent postoperative pneumonia in univariate and multivariate analysis [hazard ratio (HR) 3.30, 95% confidence interval (CI) 1.032-10.033, p = 0.0443]. Additionally, these patients were significantly correlated with worse overall survival (OS) in univariate and multivariate analyses (HR 2.75, 95% CI 1.018-7.426, p = 0.0460). Furthermore, we investigated the relationship between OS and postoperative pneumonia to elucidate why low preoperative transferrin, which is an independent risk factor for postoperative pneumonia, leads to poor prognosis. Patients with postoperative pneumonia were strongly associated with a shorter OS (p = 0.0099). Preoperative serum transferrin levels may be a novel indicator of postoperative pneumonia and OS after esophagectomy.

Tumor necrosis factor alpha-an underestimated risk predictor in patients undergoing transcatheter aortic valve replacement (TAVR)?

BackgroundSystemic inflammation has been identified as a major cardiovascular risk factor in patients undergoing transcatheter aortic valve replacement (TAVR), yet currently, it is not adequately portrayed in scores for pre‐interventional risk assessment. The aim of this study was to investigate the predictive ability of TNF‐α in TAVR.MethodsA total of 431 patients undergoing transfemoral TAVR were enrolled in this study. Blood samples were drawn prior to intervention, 24 h post‐intervention, 4, 5, and 7 days post‐intervention, and 1, 3, and 6 months post‐TAVR.ResultsIn a univariate Cox proportional hazard analysis, plasma concentrations of TNF‐α after 24 h and after 5 days were associated with mortality after 12 months (after 24 h: HR 1.002 (1.000–1.004), p = 0.028; after 5d: HR 1.003 (1.001–1.005), p = 0.013). This association remained significant even after correction for confounders in a multivariate Cox regression analysis. Additionally, cut‐offs were calculated. Patients above the cut‐off for TNF‐α after 5d had a significantly worse 12‐month mortality than patients below the cut‐off (18.8% vs. 2.8%, p = 0.046).ConclusionPlasma levels of TNF‐α after 24 h and 5 days were independently associated with 12‐month mortality in patients undergoing TAVR. Thus, TNF‐α could represent a novel biomarker for enhanced risk stratification in these patients.

Total arch replacement in octogenarians.

OBJECTIVESWe investigated the effect of a preoperative age ≥80 years on postoperative outcomes in patients who underwent isolated elective total arch replacement using mild hypothermic lower body circulatory arrest with bilateral antegrade selective cerebral perfusion.METHODSA total of 140 patients who had undergone isolated elective total arch replacement between January 2007 and December 2020 were enrolled in the present study. We compared postoperative outcomes between 30 octogenarian patients (≥80 years old; Octogenarian group) and 110 non-octogenarian patients (≤79 years old; Non-Octogenarian group).RESULTSOverall 30-day mortality and hospital mortality were 0% in both groups, and there was no significant difference in overall survival between the 2 groups (log-rank test, P = 0.108). Univariable Cox proportional hazard analysis showed that age as continuous variable was only the predictor of mid-term all-cause death (hazard ratio 1.08, 95% confidence interval 1.01–1.16; P = 0.037), but not in the Octogenarians subgroup (P = 0.119).CONCLUSIONSPreoperative age ≥80 years is not associated with worse outcomes postoperatively after isolated elective total arch replacement with mild hypothermic lower body circulatory arrest and bilateral antegrade selective cerebral perfusion.

High Visceral Adipose Tissue Density Correlates With Unfavorable Outcomes in Patients With Intermediate-Stage Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

Objectives: This study aimed to evaluate the association between different body composition features with prognostic outcomes of intermediate stage hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE).Methods: The areas and density of skeletal muscle area (SM) and adipose tissue [subcutaneous (SAT); visceral (VAT)] were calculated on the pre-TACE CT scans. Overall survival (OS) and progression-free survival (PFS) curves were calculated using the Kaplan–Meier method and compared with log-rank test. The discrimination and performance of body composition features were measured by area under time-dependent receiver operating characteristic (ROC) curve. Univariate and multivariate Cox proportional hazard analyses were applied to identify the association between body composition parameters and outcomes.Results: A significant prolonged OS and PFS was displayed by Kaplan–Meier curve analysis for HCC patients with VAT HU below −89.1 (25.1 months, 95% CI: 18.1–32.1 vs. 17.6 months, 95% CI: 16.3–18.8, p < 0.0001, 15.4 months, 95% CI: 10.6–20.2 vs. 6.6 months, 95% CI: 4.9–8.3, p < 0.0001, respectively). The 1-, 2-, 3-, and 5-year OS area under the curve (AUC) values of the VAT HU were higher than the other body composition parameters. Meanwhile, it is also found that 3-, 6-, 9-, and 12-month PFS AUC values of VAT HU were the highest among all the parameters. Univariate and multivariate Cox-regression analysis suggested a significant association between VAT density and outcomes (OS, HR: 1.015, 95% CI: 1.004–1.025, p = 0.005, PFS, HR: 1.026, 95% CI: 1.016–1.036, p < 0.0001, respectively).Conclusion: The VAT density could provide prognostic prediction value and may be helpful to stratify the intermediate stage HCC patients.

Influence of sarcopenia, clinical data, and 2-[18F] FDG PET/CT in outcome prediction of patients with early-stage adenocarcinoma esophageal cancer.

To determine the prognostic value of sarcopenia measurements done on staging 2-[18F] FDG PET/CT together with metabolic activity of the tumor in patients with adenocarcinoma esophagogastric cancer with surgical treatment. Patients with early-stage, surgically treated esophageal adenocarcinoma and available pre-treatment 2-[18F] FDG PET/CT were included. The standard uptake value (SUV) and SUV normalized by lean body mass (SUL) were recorded. Skeletal muscle index (SMI) was measured at the L3 level on the CT component of the PET/CT. Sarcopenia was defined as SMI < 34.4cm2/m2 in women and < 45.4cm2/m2 in men. Of the included 145 patients. 30% were sarcopenic at baseline. On the univariable Cox proportional hazards analysis, ECOG, surgical T and N staging, lymphovascular invasion (LVI) positive lymph nodes, and sarcopenia were significant prognostic factors concerning RFS and OS. On multivariable Cox regression analysis, surgical N staging (p = 0.025) and sarcopenia (p = 0.022) remained significant poor prognostic factors for OS and RFS. Combining the clinical parameters with the imaging-derived nutritional evaluation of the patient but not metabolic parameters of the tumor showed improved predictive ability for OS and RFS. Combining the patients' imaging-derived sarcopenic status with standard clinical data, but not metabolic parameters, offered an overall improved prognostic value concerning OS and RFS.

Nomograms predict survival of patients with lymph node-positive, luminal a breast cancer

BackgroundTo develop nomograms for the prediction of the 1-, 3-, and 5-year overall survival (OS) and breast cancer-specific survival (BCSS) for patients with lymph node positive, luminal A breast cancer.MethodsThirty-nine thousand fifty-one patients from The Surveillance, Epidemiology, and End Results (SEER) database were included in our study and were set into a training group (n = 19,526) and a validation group (n = 19,525). Univariate analysis and Cox proportional hazards analysis were used to select variables and set up nomogram models on the basis of the training group. Kaplan-Meier curves and the log-rank test were adopted in the survival analysis and curves plotting. C-index, calibration plots and ROC curves were used to performed internal and external validation on the training group and validation group.ResultsFollowing independent factors were included in our nomograms: Age, marital status, grade, ethnic group, T stage, positive lymph nodes numbers, Metastasis, surgery, radiotherapy, chemotherapy. In both the training group and testing group, the calibration plots show that the actual and nomogram-predicted survival probabilities are consistent greatly. The C-index values of the nomograms in the training and validation cohorts were 0.782 and 0.806 for OS and 0.783 and 0.804 for BCSS, respectively. The ROC curves show that our nomograms have good discrimination.ConclusionsThe nomograms may assist clinicians predict the 1-, 3-, and 5-year OS and BCSS of patients with lymph node positive, luminal A breast cancer.

Identification of a prognostic ferroptosis-related lncRNA signature in the tumor microenvironment of lung adenocarcinoma

Ferroptosis is closely linked to various cancers, including lung adenocarcinoma (LUAD); however, the factors involved in the regulation of ferroptosis-related genes are not well established. In this study, we identified and characterized ferroptosis-related long noncoding RNAs (lncRNAs) in LUAD. In particular, a coexpression network of ferroptosis-related mRNAs and lncRNAs from The Cancer Genome Atlas (TCGA) was constructed. Univariate and multivariate Cox proportional hazards analyses were performed to establish a prognostic ferroptosis-related lncRNA signature (FerRLSig). We obtained a prognostic risk model consisting of 10 ferroptosis-related lncRNAs: AL606489.1, AC106047.1, LINC02081, AC090559.1, AC026355.1, FAM83A-AS1, AL034397.3, AC092171.5, AC010980.2, and AC123595.1. High risk scores according to the FerRLSig were significantly associated with poor overall survival (hazard ratio (HR) = 1.412, 95% CI = 1.271–1.568; P < 0.001). Receiver operating characteristic (ROC) curves and a principal component analysis further supported the accuracy of the model. Next, a prognostic nomogram combining FerRLSig with clinical features was established and showed favorable predictive efficacy for survival risk stratification. In addition, gene set enrichment analysis (GSEA) revealed that FerRLSig is involved in many malignancy-associated immunoregulatory pathways. Based on the risk model, we found that the immune status and response to immunotherapy, chemotherapy, and targeted therapy differed significantly between the high-risk and low-risk groups. These results offer novel insights into the pathogenesis of LUAD, including the contribution of ferroptosis-related lncRNAs, and reveal a prognostic indicator with the potential to inform immunological research and treatment.

Preoperative iron status is a prognosis factor for stage II and III colorectal cancer.

Iron deficiency anemia is represented in colorectal cancer (CRC) patients. Iron surplus load to increase non-transferrin bound iron (NTBI), and NTBI promotes cancer progression and influences microbiota. This study investigated whether preoperative serum iron status was associated with prognosis after CRC resection. We evaluated preoperative iron and transferrin saturation (TSAT), which was calculated as iron divided by total iron-binding capacity, in 327 patients who underwent surgery for Stage II-III CRC. Fe < 60μg/dl and TSAT > 40% were defined as low and high iron, respectively. The associations between iron status and overall survival (OS) were evaluated in univariate and multivariate Cox proportional hazards analysis. Of the 327 patients, 179 (54.7%), 124 (37.9%) and 24 (7.3%) had low, normal and high iron, respectively. In univariate analysis, low iron was associated with shorter OS (hazard ratio [HR] 2.821, 95% confidence interval [CI] 1.451-5.485, P = 0.002). High iron was also associated with shorter OS (HR 3.396, 95% CI 1.359-8.489, P = 0.009). In multivariate analysis, high age (P = 0.002), depth of invasion pT4 (P = 0.012), lymph-node metastasis presence (P = 0.035), low albumin (P = 0.011), low iron (HR 2.282, 95% CI 1.163-4.478, P = 0.016) and high iron (HR 3.757, 95% CI 1.486-9.494 P = 0.005) were independently associated with shorter OS. High iron was associated with the amount of intratumoral Fusobacterium nucleatum compared with normal iron. Both low and high preoperative iron in Stage II-III CRC patients were associated with unfavorable OS in univariate and multivariate analyses.

Early risk-assessment of patients with nasopharyngeal carcinoma: the added prognostic value of MR-based radiomics

ObjectivesTo assess the additive prognostic value of MR-based radiomics in predicting progression-free survival (PFS) in patients with nasopharyngeal carcinoma (NPC) MethodsPatients newly diagnosed with non-metastatic NPC between June 2006 and October 2019 were retrospectively included and randomly grouped into training and test cohorts (7:3 ratio). Radiomic features (n=213) were extracted from T2-weighted and contrast-enhanced T1-weighted MRI. The patients were staged according to the 8th edition of American Joint Committee on Cancer Staging Manual. The least absolute shrinkage and selection operator was used to select the relevant radiomic features. Univariate and multivariate Cox proportional hazards analyses were conducted for PFS, yielding three different survival models (clinical, stage, and radiomic). The integrated time-dependent area under the curve (iAUC) for PFS was calculated and compared among different combinations of survival models, and the analysis of variance was used to compare the survival models. The prognostic performance of all models was validated using a test set with integrated Brier scores. ResultsThis study included 81 patients (training cohort=57; test cohort=24), and the mean PFS was 57.5 ± 43.6 months. In the training cohort, the prognostic performances of survival models improved significantly with the addition of radiomics to the clinical (iAUC, 0.72–0.80; p=0.04), stage (iAUC, 0.70–0.79; p=0.001), and combined models (iAUC, 0.76–0.81; p<0.001). In the test cohort, the radiomics and combined survival models were robustly validated for their ability to predict PFS. ConclusionIntegration of MR-based radiomic features with clinical and stage variables improved the prediction PFS in patients diagnosed with NPC.

Construction of Immune-Associated Nomogram for Predicting the Recurrence Survival Risk of Stage I Cervical Cancer.

Background Various studies reported that the prognosis of patients with cervical cancer (CC) was significantly associated with immunity, whereas limited studies have explored whether immune-associated genes could be classifiers for recurrence-free survival (RFS) of stage I CC. Thus, an improved immune-related gene signature for stage I CC patients' prognosis is urgently required. Materials and Methods We retrospectively analyzed the gene expression profiles of stage I CC patients in the GSE44001 set from the Gene Expression Omnibus (GEO) database. The stage I CC patients were randomly divided into the training group and the internal validation group. The training patients were adopted to develop a prognostic immune gene-based signature; meanwhile, the internal validation patients were used to validate the power of the selected immune gene-related signature using univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis. The accuracy and reliability of the immune gene-related signature were evaluated based on Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) curves. Results High power of the 8-immune gene signature was found on the basis of ROC analysis (AUC at 1, 3, and 5 years were exhibited in the internal validation group (0.702, 0.715, and 0.728, respectively), external validation group (0.702, 0.825, and 0.842, respectively), and entire GEO dataset (0.840, 0.894, and 0.852, respectively)). Besides, C-index, ROC, calibration plots, and decision curve analysis (DCA) also acted well in our nomogram, suggestive of a high ability of the nomogram to elevate the prognostic prediction of stage I CC patients. Conclusions In this study, we successfully constructed an integrated 8-immune gene-based signature which could accurately identify patients with low prognostic risk from those with high prognostic risk. In addition, we developed an immune-related nomogram which can elevate the prognostic prediction of stage I CC patients.

An easy-to-operate web-based calculator for predicting the progression of chronic kidney disease

BackgroundThis study aimed to establish and validate an easy-to-operate novel scoring system based on simple and readily available clinical indices for predicting the progression of chronic kidney disease (CKD).MethodsWe retrospectively evaluated 1045 eligible CKD patients from a publicly available database. Factors included in the model were determined by univariate and multiple Cox proportional hazard analyses based on the training set.ResultsIndependent prognostic factors including etiology, hemoglobin level, creatinine level, proteinuria, and urinary protein/creatinine ratio were determined and contained in the model. The model showed good calibration and discrimination. The area under the curve (AUC) values generated to predict 1-, 2-, and 3-year progression-free survival in the training set were 0.947, 0.931, and 0.939, respectively. In the validation set, the model still revealed excellent calibration and discrimination, and the AUC values generated to predict 1-, 2-, and 3-year progression-free survival were 0.948, 0.933, and 0.915, respectively. In addition, decision curve analysis demonstrated that the model was clinically beneficial. Moreover, to visualize the prediction results, we established a web-based calculator (https://ncutool.shinyapps.io/CKDprogression/).ConclusionAn easy-to-operate model based on five relevant factors was developed and validated as a conventional tool to assist doctors with clinical decision-making and personalized treatment.

Utility of the High-Sensitivity Modified Glasgow Prognostic Scores for Oropharyngeal Carcinoma.

ObjectiveThere is increasing evidence that the high-sensitivity modified Glasgow prognostic scores are inflammatory indices that can predict survival for many cancer types. However, there is limited information regarding their prognostic values in cases of head and neck cancer. This study aimed to evaluate whether the high-sensitivity modified Glasgow prognostic scores could predict outcomes among patients with oropharyngeal squamous cell carcinoma (OPC).Study DesignRetrospective study.SettingUniversity hospital.MethodsWe reviewed the records of 106 patients with histologically confirmed OPC between March 2009 and June 2020. The high-sensitivity modified Glasgow prognostic scores were calculated as 0 (C-reactive protein [CRP] concentration: ≤0.3 mg/dL), 1 (CRP concentration >0.3 mg/dL and albumin concentration ≥3.5 mg/dL), or 2 (CRP concentration >0.3 mg/dL and albumin concentration <3.5 mg/dL). Univariate and multivariable Cox proportional hazard analyses were performed for overall survival (OS) and disease-free survival (DFS).ResultsForty-four of these patients had human papillomavirus (HPV)–positive OPC, and 62 had HPV-negative OPC, and these populations were analyzed separately. The high-sensitivity modified Glasgow prognostic score was significantly associated with age, performance status, and HPV. On univariate analysis, high-sensitivity modified Glasgow prognostic score showed associations with OS and DFS in both subpopulations. Moreover, on multivariable analysis, the high-sensitivity modified Glasgow prognostic score showed associations with OS and DFS in both subpopulations. Poor performance status predicted OS in both subpopulations.ConclusionWe conclude that the high-sensitivity modified Glasgow prognostic score is useful as an independent prognostic factor in OPC.

Development and Validation of Prognostic Nomograms Based on Gross Tumor Volume and Cervical Nodal Volume for Nasopharyngeal Carcinoma Patients With Concurrent Chemoradiotherapy.

PurposeOur study aimed to establish and validate prognostic nomograms based on gross tumor volume (GTV) and cervical nodal volume (CNV) for nasopharyngeal carcinoma (NPC) patients treated with two cycles of concurrent chemoradiotherapy (CCRT).MethodsFrom 2012 to 2015, 620 eligible patients who received radical treatment at the Cancer Hospital of Shantou University Medical College were recruited for a nomogram study. Variables were determined in a training set of 463 patients from 2012 to 2014 by X-tile analysis, univariate and multivariate Cox proportional hazard analyses, and the least absolute shrinkage and selection operator (LASSO). Another cohort of 157 patients in 2015 was validated with bootstrap resampling. The concordance index (C-index) and calibration curves were applied to assess its predictive discriminative and accuracy ability, while decision curve analysis (DCA), X-tile analysis and Kaplan–Meier curve for clinical application.ResultsIndependent prognostic variables for overall survival (OS) were age, GTV, CNV, cranial nerve, positive cervical lymph node laterality below the caudal border of cricoid cartilage (LNBC), and were selected for the nomogram. Optimal prognostic factors including Karnofsky performance status (KPS), age, GTV, CNV, LNBC were incorporated in the nomogram for progression-free survival (PFS). In the training set, the C-index of our nomograms for OS and PFS were 0.755 (95% CI, 0.704 to 0.807) and 0.698 (95% CI, 0.652 to 0.744). The calibration curve showed good agreement between nomogram-predicted and actual survival. DCA indicated that our nomograms were of clinical benefit.ConclusionOur nomograms are capable of effective prognostic prediction for patients with NPC.

Central Nervous System Relapse in Diffuse Large B Cell Lymphoma—Predictors at Diagnosis

Background Central nervous system (CNS) relapse of diffuse large B cell lymphoma (DLBCL) is an infrequent outcome with very poor prognosis. Initial studies have identified risk factors for CNS relapse and the CNS international prognostic score ((CNS-IPI) (Schmitz et al, JCO 2016) has been validated in various cohorts. Biologic characteristics of the disease are not included in the derivation of this model. We sought to validate this risk factor model in our single center DLBCL population in search for additional disease - specific factors that could further improve prediction of CNS relapse.Methods The hematologic malignancies database of the University Hospitals Seidman Cancer Center was accessed to identify newly diagnosed DLBCL patients between 2002 and 2014. Patients with extra-nodal CNS involvement at diagnosis were excluded. Through retrospective chart review data, we identified patient and disease characteristics, and outcomes data including response, relapse and death was collected. Patients who underwent therapy and had follow up data were included for final analysis. Univariate Cox proportional hazards analysis was conducted on the risk factors and those reaching statistical significance (p < 0.05) were selected for inclusion in multivariate proportional hazards model to help identify predictors for CNS relapse. CNS IPI score was applied to our population and cumulative incidence (with death as competing risk) was used to estimate the incidence of CNS relapse with the Gray test performed for comparisons between groups.Results: Five hundred and twenty-four patients were included for final analysis. Median age in our cohort was 64 years, with 312 (59.5 %) patients above the age of 60 years. 322 (63 %) patients had stage (III-IV), and 220 patients (37%) had elevated LDH at diagnosis. Two hundred and eighty five patients had extra-nodal disease involvement at the time of diagnosis with 88 patients involving more than one site. Baseline patient and disease characteristics are listed in Table 1. Four hundred (76%) patients received R CHOP as first line therapy, 395 patients achieved complete remission with first line therapy. At a median follow up of 64 months, 187 patients died and 171 patients had relapsed.Twenty-one patients developed CNS relapse in the follow up period, at median of 8.2 months after treatment initiation (95% CI 6.2-9.6) months. Applying the CNS-IPI risk scoring among the evaluable patients, 149 patients (36%) were found to be low risk (0-1 factors), 222 patients (53%) were intermediate risk (2-3 factors) and 47 patients (9%) were high risk (4-6 factors) for CNS relapse. Univariate analysis showed advanced stage (stage III-IV), number of extra-nodal sites involved, liver involvement, non- GCB subtype, translocation t (14; 18) and body mass index were significantly associated with CNS relapse (p<0.05). In multivariate analysis, only non- GCB subtype and translocation t (14; 18) (p = 0.023 and 0.028 respectively) were significant. Table 2 summarizes the results of Cox proportional hazards analysis.We evaluated the cumulative incidence of CNS relapse in the high-risk group, defined as CNS-IPI >1, (n=269, 64%). The 2-year CNS relapse cumulative incidence was at 5.1 % (95% CI: 2.8- 9%) compared to 0% for patients with CNS IPI ≤ 1 (p=0.027) (Figure 1).Median survival after CNS relapse was 3.6 months (0 - 150.2 months). Overall survival from start of initial therapy was 16 months (95% CI 9.5 -81.9 months) for patients with CNS relapse vs 170 months (95% CI 120.3 months - not reached), p<0.001]. (Figure 2)SummaryPrognosis of CNS relapsed of DLBCL is very poor. CNS IPI score helps identify a cohort that may benefit from CNS prophylaxis, and may help avoid unnecessary diagnostic and therapeutic intervention in the low risk cohort, i.e., CNS- IPI score <1. Hepatic involvement at diagnosis may be an additional clinical characteristic associated with high risk of CNS relapse. Biological features including non-GCB subtype and translocation t (14; 18) are novel risk factors that should be considered in the development of future risk models. [Display omitted] DisclosuresMalek:Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau. Cooper:Novartis: Research Funding. de Lima:Celgene Corporation: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees. Caimi:Seattle Genetics: Equity Ownership; Abbvie: Equity Ownership; Incyte: Equity Ownership; Celgene: Speakers Bureau.

Prognostic Impact of Morphological Cellularity in Early Assessment Bone Marrow Biopsy after 7+3 Induction in Patients with Acute Myeloid Leukemia

Background:Blast clearance in early assessment bone marrow biopsy (BMBx) is well studied as a potential prognostic factor for newly diagnosed acute myeloid leukemia (AML) patients (pts). However, prognostic impact of morphological cellularity in early assessment BMBx remains unclear.Methods:We retrospectively identified newly diagnosed AML pts, treated at University Hospitals Seidman Cancer Center between 2003 and 2016, who underwent early assessment BMBx after median of 13 days (range: 12 - 17) from initiation of 7+3 induction chemotherapy. Eventual outcome of induction was defined per Cheson criteria. Risk groups were determined by combining cytogenetic and molecular data based on the National Comprehensive Cancer Network guidelines. Overall survival (OS), calculated from date of diagnosis, and relapse free survival (RFS), calculated from date of first complete remission (CR), were estimated by the Kaplan-Meier method and compared by the log-rank test. Risk factors identified as having statistical significance on univariate Cox proportional hazards analysis (p<0.05) were selected for multivariate analysis.Results: We screened 501 newly diagnosed AML pts and identified 183 AML pts who meet our inclusion criteria for analysis. Median age at diagnosis was 58.3 (range: 25.8 - 76.2). Patient and treatment characteristics are listed in Table 1.After analyzing different cut-off points, ≥10% morphological cellularity in early assessment BM biopsy yielded greatest differential in OS and RFS. Therefore optimal and suboptimal response cohorts were defined as <10% and ≥10% cellularity in early assessment BMBx, respectively. One hundred (55%) pts had optimal and 72 (39%) pts had suboptimal response. Eleven (6%) pts were unclassifiable because cellularity was not mentioned as a numerical value (Figure 1). In the optimal response cohort; 5 (2%) pts underwent second induction after early assessment BMBx and 95 (98%) pts were observed, with CR rate of 80% and 86%, respectively. Among 13 (14%) pts who didn't achieve CR after observation, 12 pts underwent second induction, with CR rate of 25%, and 1 pt died before second induction. In the suboptimal response cohort; 40 (56%) pts underwent second induction after early assessment BMBx and 29 (40%) pts were observed, with CR rate of 70% and 59%, respectively. Twelve (41%) pts who didn't achieve CR after observation underwent second induction, with CR rate of 42%. Overall 50 (69%) pts in the suboptimal response cohort and 88 (88%) pts in the optimal response cohort ultimately achieved CR after either first or second induction.Among observed patients, who did not receive early 2nd induction, ≥10% cellularity in early assessment BMBx was reliable as a predictive tool for CR (specificity 83%, negative predictive value 86%) but it was not reliable as a predictive tool for no-CR (sensitivity 48%, positive predictive value 41%).Median follow-up of pts was 28 months since diagnosis. Two-year OS for pts with optimal and suboptimal response at early assessment BMBx was 59.9% (CI 50.1% - 71.5%) and 33.3% (CI 23.4% - 47.3%), respectively (p= 0.001) (Figure 2A). When we censor pts at their first transplant to remove effect of transplant on survival curves, 2-year OS for pts with optimal and suboptimal response at early assessment BMBx was 77.8% (CI 65.7% - 92.0%) and 44.6% (CI 27.1% - 73.4%), respectively (p= 0.003) (Figure 2B). Two-year RFS for pts with optimal and suboptimal response at early assessment BMBx was 49.5% (CI 39.6% - 61.9%) and 29.9% (CI 19.6% - 45.6%), respectively (p= 0.015) (Figure 2C). On univariate analysis, poor-risk group by cytogenetic and molecular data, hemoglobin (<8.8 g/dL), secondary AML, >5% blast and ≥10% cellularity at early assessment BMBx showed statistically significant correlation with OS (Table 2). On multivariate analysis, only poor-risk group and ≥10% cellularity at early assessment BMBx remained to be statistically significant predictors of OS.Conclusions:In our cohort of pts with AML, ≥10% morphological cellularity in early assessment BMBx provided strong independent predictive value for OS, whereas >5% blast was not an independent risk factor. Our findings indicate that ≥10% cellularity in early assessment BMBx can be part of overall risk stratification tools and the definition of hypoplasia should include <10% cellularity when considering early assessment biopsies. [Display omitted] DisclosuresCooper:Novartis: Research Funding. Caimi:Incyte: Equity Ownership; Celgene: Speakers Bureau; Seattle Genetics: Equity Ownership; Abbvie: Equity Ownership. Malek:Celgene: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees. De Lima:Pfizer: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Research Funding.

Prognostic Biomarker-Based Identification of Drugs for Managing the Treatment of Endometrial Cancer.

Uterine corpus endometrial carcinoma (UCEC) causes thousands of deaths per year. To improve the overall survival of patients with UCEC, there is a need to identify prognostic biomarkers and potential drugs. The aim of this study was twofold: the identification of prognostic gene signatures from expression profiles of pattern recognition receptor (PRR) genes and identification of the most effective existing drugs using the prognostic gene signature. This study was based on the expression profile of PRR genes of 541 patients with UCEC obtained from The Cancer Genome Atlas. Key prognostic signatures were identified using various approaches, including survival analysis, network, and clustering. Hub genes were identified by constructing a co-expression network. Representative genes were identified using k-means and k-medoids-based clustering. Univariate Cox proportional hazard (PH) analysis was used to identify survival-associated genes. 'cmap2' was used to identify potential drugs that can suppress/enhance the expression of prognostic genes. Models were developed using hub genes and achieved a maximum hazard ratio (HR) of 1.37 (p = 0.294). Then, a clustering-based model was developed using seven genes (HR 9.14; p = 1.49 × 10-12). Finally, a nine gene-based risk stratification model was developed (CLEC1B, CLEC3A, IRF7, CTSB, FCN1, RIPK2, NLRP10, NLRP9, and SARM1) and achieved HR 10.70; p = 1.1 × 10-12. The performance of this model improved significantly in combination with the clinical stage and achieved HR 15.23; p = 2.21 × 10-7. We also developed a model for predicting high-risk patients (survival ≤ 4.3 years) and achieved an area under the receiver operating characteristic curve (AUROC) of 0.86. We identified potential immunotherapeutic agents based on prognostic gene signature: hexamethonium bromide and isoflupredone. Several novel candidate drugs were suggested, including human interferon-α-2b, paclitaxel, imiquimod, MESO-DAP1, and mifamurtide. These biomolecules and repurposed drugs may be utilised for prognosis and treatment for better survival.

Long-term outcomes after the paediatric Ross and Ross-Konno procedures.

The Ross procedure is an attractive option for the management of aortic valve disease in paediatric patients. We reviewed our experience with the paediatric Ross procedure to determine survival and freedom from reoperation in the third decade after surgery. We reviewed the data of 124 paediatric patients [71% male, median age at time of surgery 11.1 years (interquartile range 6-14.8 years); 63.7% bicuspid aortic valve], who underwent the Ross procedure at 2 tertiary centres from April 1991 to April 2020. The Ross-Konno procedures were performed on 14 (11.3%) patients. Deaths were cross-checked with the national health insurance database, and survival status was available for 96.8% of the patients. The median follow-up time was 12.1 years (interquartile range 3-18 years). There were 3 early and 6 late deaths. All early deaths occurred in patients aged <1 year at the time of surgery. The 25-year survival was 90.3%. Actuarial freedom from reoperation (linearized rates in parentheses) was as follows: Autograft reoperation was 90.8% (0.48%/patient-year) and right ventricular outflow tract (RVOT) reoperation was 67% (2.07%/patient year) at 25 years. The univariable Cox-proportional hazard analysis revealed younger age at time of surgery (P < 0.001), smaller implanted valve size (P < 0.001) and the use of a xenograft rather than a homograft (P < 0.001) as predictors of RVOT reoperation. At multivariable Cox-proportional hazard analysis, only age was an independent risk factor for RVOT reoperation (P = 0.041). The Ross and the Ross-Konno procedures are associated with good outcomes in paediatric patients. Reoperation of the RVOT is frequent and associated with younger age.

Prognostic value of the left ventricular - left atrial volume ratio assessed using three-dimensional echocardiography with fully automated analytical software

Backgroundwe investigated the prognostic value of a new 3D echocardiography (3DE) parameter, the left ventricular-left atrial volume ratio (LVLAVR) in a diverse group of subjects. Methods3DE full-volume datasets were analyzed in 307 patients using fully automated LV and LA quantification software (Dynamic Heart Model, Philips Medical Systems, Andover, MA, USA), which generated LV and LA volume curves using artificial intelligence and 3D speckle tracking technology. We measured LVLAVR at LV end-diastole (edLVLAVR; LV end-diastolic volume / LA minimal volume), LVLAVR at LV end-systole (esLVLAVR: LV end-systolic volume / LA maximal volume), and their differences (ΔLVLAVR: edLVLAVR – esLVLAVR). No manual editing was performed on data of any patient. The primary endpoint was a major adverse cardiac event (MACE), including cardiac death, heart failure resulting in hospitalization, myocardial infarction, or ventricular tachyarrhythmia. Resultsfeasibility of LVLAVR measurements was 90%. During a median follow-up of 21 months, 43 patients developed a primary endpoint. Univariate Cox proportional hazard analysis revealed that edLVLAVR [hazard ratio (HR): 0.72, p < 0.01] and ΔLVLAVR (HR: 0.62, p < 0.01) were significantly associated with MACE. Median values of both edLVLAVR (4.59) and ΔLVLAVR (2.90) successfully stratified patients into high- and low-risk populations for future MACEs. ΔLVLAVR was still significantly associated with MACEs after adjusting for age, chronic kidney disease (CKD) and LV ejection fraction or after adjusting for age, CKD, and E/ε’. ConclusionsLVLAVR provided incremental value over traditional LV systolic and diastolic function parameters to predict future adverse outcomes. The analysis was fully automated, thereby eliminating measurement variability.

The LDL-C/ApoB ratio predicts major cardiovascular events in patients with established atherosclerotic cardiovascular disease

Background and aimsThe low density lipoprotein cholesterol to Apolipoprotein B (LDL-C/ApoB) ratio is a validated proxy for low density lipoprotein (LDL) particle size that can be easily calculated from a standard lipid/apolipoprotein profile. Whether it is predictive of cardiovascular events in patients with established atherosclerosis is not known and is addressed in the present investigation. MethodsWe determined the LDL-C/ApoB ratio in a cohort of 1687 subjects with established atherosclerosis. Prospectively, major cardiovascular events (MACE) including cardiovascular death, non-fatal myocardial infarction and non-fatal stroke were recorded over a period of 9.9 ± 4.6 years. The study covers >16,000 patient-years. ResultsAt baseline, the LDL-C/ApoB ratio was 1.36 ± 0.28 in our cohort. During follow up, a total of 558 first MACE were recorded. The LDL-C/ApoB ratio predicted MACE in univariate Cox proportional hazard analysis (HR 0.90 [0.82–0.98]; p = 0.014); this finding was confirmed after adjustment for age, gender, intensity of statin treatment, hypertension, history of smoking, type 2 diabetes, body mass index and ApoB (HR 0.87 [0.78–0.97]; p = 0.013). ConclusionsThe LDL-C/ApoB ratio is independently predictive of MACE in subjects with established atherosclerosis.