Overall Survival Probability Of Patients Research Articles

Perceval-S over time. Clinical outcomes after ten years of usage

BackgroundPerceval-S has become a reliable and commonly used option in surgical aortic valve replacement (AVR) since its first implantation in humans 15 years ago. Despite the fact that this aortic valve has been proven efficient enough in the short and mid-term period, there is still lack of evidence for the long-term outcomes.Materials and methodsThis is an observational retrospective study in a high-volume cardiovascular center. Pertinent data were collected for all the patients in whom Perceval-S was implanted from 2013 to 2020.ResultsThe total number of patients was 205 with a mean age 76.4 years. Mean survival time was 5.5 years (SE = 0.26). The overall survival probability of patients undergoing aortic valve replacement with Perceval-S at 6 months was 91.0% (Standard Error SE = 2.0%), at one year 88.4% (SE = 2.3%) and at 5-years 64.8% (SE = 4.4%). A detrimental cardiac event leading to death was the probable cause of death in 35 patients (55.6%). The initiation of Transcatheter Aortic Valve Replacement (TAVR) program in our center in 2017 was associated with a decline in the number of very high-risk patients treated with sutureless bioprosthesis. This fact is demonstrated by the significant shift towards lower surgical risk cases, as median Euroscore II was reduced from 5,550 in 2016 to 3,390 in 2020. Mini sternotomy was implemented in 79,5% of cases favoring less invasive approach. Low incidence of reinterventions, patient prosthesis mismatch and structural valve degeneration was detected.ConclusionsThe survival rate after aortic valve replacement with implantation of Perceval-S is satisfactory in the long-term follow-up. Cases of bioprosthesis dysfunction were limited. Mini sternotomy was used in the majority of cases. TAVR initiation program impacted on the proportion of patients treated with Perceval-S with reduction of high-risk patients submitted to surgery.

Deep learning model based on multi-lesion and time series CT images for predicting the benefits from anti-HER2 targeted therapy in stage IV gastric cancer.

To develop and validate a deep learning model based on multi-lesion and time series CT images in predicting overall survival (OS) in patients with stage IV gastric cancer (GC) receiving anti-HER2 targeted therapy. A total of 207 patients were enrolled in this multicenter study, with 137 patients for retrospective training and internal validation, 33 patients for prospective validation, and 37 patients for external validation. All patients received anti-HER2 targeted therapy and underwent pre- and post-treatment CT scans (baseline and at least one follow-up). The proposed deep learning model evaluated the multiple lesions in time series CT images to predict risk probabilities. We further evaluated and validated the risk score of the nomogram combining a two-follow-up lesion-based deep learning model (LDLM-2F), tumor markers, and clinical information for predicting the benefits from treatment (Nomo-LDLM-2F). In the internal validation and prospective cohorts, the one-year AUCs for Nomo-LDLM-2F using the time series medical images and tumor markers were 0.894 (0.728-1.000) and 0.809 (0.561-1.000), respectively. In the external validation cohort, the one-year AUC of Nomo-LDLM-2F without tumor markers was 0.771 (0.510-1.000). Patients with a low Nomo-LDLM-2F score derived survival benefits from anti-HER2 targeted therapy significantly compared to those with a high Nomo-LDLM-2F score (all p < 0.05). The Nomo-LDLM-2F score derived from multi-lesion and time series CT images holds promise for the effective readout of OS probability in patients with HER2-positive stage IV GC receiving anti-HER2 therapy. The deep learning model using baseline and early follow-up CT images aims to predict OS in patients with stage IV gastric cancer receiving anti-HER2 targeted therapy. This model highlights the spatiotemporal heterogeneity of stage IV GC, assisting clinicians in the early evaluation of the efficacy of anti-HER2 therapy. • Multi-lesion and time series model revealed the spatiotemporal heterogeneity in anti-HER2 therapy. • The Nomo-LDLM-2F score was a valuable prognostic marker for anti-HER2 therapy. • CT-based deep learning model incorporating time-series tumor markers improved performance.

Survival and predictors of breast cancer mortality in South Ethiopia: A retrospective cohort study.

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in over 100 countries. In March 2021, the World Health Organization called on the global community to decrease mortality by 2.5% per year. Despite the high burden of the disease, the survival status and the predictors for mortality are not yet fully determined in many countries in Sub-Saharan Africa, including Ethiopia. Here, we report the survival status and predictors of mortality among breast cancer patients in South Ethiopia as crucial baseline data to be used for the design and monitoring of interventions to improve early detection, diagnosis, and treatment capacity. A hospital-based retrospective cohort study was conducted among 302 female breast cancer patients diagnosed from 2013 to 2018 by reviewing their medical records and telephone interviews. The median survival time was estimated using the Kaplan-Meier survival analysis method. A log-rank test was used to compare the observed differences in survival time among different groups. The Cox proportional hazards regression model was used to identify predictors of mortality. Results are presented using the crude and adjusted as hazard ratios along with their corresponding 95% confidence intervals. Sensitivity analysis was performed with the assumption that loss to follow-up patients might die 3 months after the last hospital visit. The study participants were followed for a total of 4,685.62 person-months. The median survival time was 50.81 months, which declined to 30.57 months in the worst-case analysis. About 83.4% of patients had advanced-stage disease at presentation. The overall survival probability of patients at two and three years was 73.2% and 63.0% respectively. Independent predictors of mortality were: patients residing in rural areas (adjusted hazard ratio = 2.71, 95% CI: 1.44, 5.09), travel time to a health facility ≥7 hours (adjusted hazard ratio = 3.42, 95% CI: 1.05, 11.10), those who presented within 7-23 months after the onset of symptoms (adjusted hazard ratio = 2.63, 95% CI: 1.22, 5.64), those who presented more than 23 months after the onset of symptoms (adjusted hazard ratio = 2.37, 95% CI: 1.00, 5.59), advanced stage at presentation (adjusted hazard ratio = 3.01, 95% CI: 1.05, 8.59), and patients who never received chemotherapy (adjusted hazard ratio = 6.69, 95% CI: 2.20, 20.30). Beyond three years after diagnosis, patients from southern Ethiopia had a survival rate of less than 60% despite treatment at a tertiary health facility. It is imperative to improve the early detection, diagnosis, and treatment capacities for breast cancer patients to prevent premature death in these women.

Increased Expression of POSTN Predicts Poor Prognosis: a Potential Therapeutic Target for Gastric Cancer

BackgroundPeriostin (POSTN) is involved in many biological processes and is associated with the occurrence and development of several cancers, while its role in gastric cancer is not clear. We aimed to demonstrate the relationship between POSTN and gastric cancer based on publicly available data from The Cancer Genome Atlas (TCGA) database. MethodsPOSTN expression data and corresponding clinical information were downloaded from TCGA database. We compared the expression of POSTN in gastric cancer samples and normal samples. POSTN-related differentially expressed genes (DEGs) were identified for further functional enrichment analysis. In addition, the relationships between POSTN expression and clinicopathological features and survival in patients with gastric cancer were also investigated through univariate and multivariate Cox regression analyses. Furthermore, a nomogram was constructed to predict the survival probability of gastric cancer patients. ResultsPOSTN expression in gastric cancer was significantly higher than that in normal gastric tissues (p < 0.001). High POSTN expression in gastric cancer was significantly related to poor prognostic features, including greater tumor extent (odds ratio [OR] = 1.638 for T3 and T4 vs. T1 and T2), worse histological type (OR = 0.329 for diffuse type vs. tubular type), and advanced histological grade (OR = 1.646 for grade 3 vs. grades 1 and 2) (all p < 0.05). The 118 identified DEGs were primarily enriched in pathways related to tumorigenesis and tumor progression, including the TGF-β signaling pathway, the WNT signaling pathway, and the signaling by VEGF. POSTN expression was positively correlated with the enrichment of the macrophages (r = 0.599, p < 0.001), helper T2 cells (r = 0.146, p = 0.005), and CD8 + T cells (r = 0.190, p < 0.001), but negatively correlated with the enrichment of Th17 cells (r = − 0.130, p = 0.012) and NK CD56bright cells. Kaplan–Meier survival analysis showed that high POSTN expression is associated with a short overall survival (hazard ratio [HR] = 1.54; p = 0.011). In the multivariate cox regression analysis, high POSTN expression was confirmed to be an independent predictor of poor overall survival (HR = 1.681; p = 0.017). The constructed nomogram can well predict the 1 and 3 years overall survival probability of patients with GC (0.696 [95% CI, 0.671–0.721]). ConclusionPOSTN plays an important role in the progression and prognosis of gastric cancer, and it may serve as a useful biomarker to predict survival in gastric cancer patients.

The Combination of Inflammatory Biomarkers as Prognostic Indicator in Salivary Gland Malignancy.

Background: The aim of this study was to investigate how the systemic inflammation response index (SIRI), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), taken individually and combined, are associated with overall survival (OS) in patients surgically treated for malignant salivary gland tumors (MSGTs). Methods: A retrospective analysis of 74 cases following surgery at our department between January 2011 and June 2018 was performed. The Receiver Operating Characteristic (ROC) curve was used to calculate the optimal cutoff values for SII, SIRI, PLR, and NLR. Survival curves of different groups at 1−3−5 years were estimated using the Kaplan−Meier method. Results: The optimal thresholds with the highest sensitivity and specificity were 3.95 for NLR, 187.6 for PLR, 917.585 for SII, and 2.045 for SIRI. The ROC curves revealed that the best combination with AUC = 0.884 was SII + SIRI. The estimated 5-year OS probability in patients with SII+ SIRI scores of 0, 1, and 2 was 96%, 87.5% and 12.5%, respectively (p < 0.001). Conclusion: SII+ SIRI can independently predict the OS of patients after MSGT surgery. The prognostic score system based on SII+ SIRI may be good clinical practice as a reference for clinical decision-making.

Clinical models to predict lymph nodes metastasis and distant metastasis in newly diagnosed early esophageal cancer patients: A population-based study.

Patients with early esophageal cancer (EC) receive individualized therapy based on their lymph node metastasis (LNM) and distant metastasis (DM) status; however, deficiencies in current clinical staging techniques and the issue of cost-effectiveness mean LNM and DM often go undetected preoperatively. We aimed to develop three clinical models to predict the likelihood of LNM, DM, and prognosis in patients with early EC. The Surveillance, Epidemiology, and End Results database was queried for T1 EC patients from 2004 to 2015. Multivariable logistic regression and Cox proportional hazards models were used to recognize the risk factors of LNM and DM, predict overall survival (OS), and develop relevant nomograms. Receiver operating characteristic (ROC)/concordance index and calibration curves were used to evaluate the discrimination and accuracy of the three nomograms. Decision curve analyses (DCAs), clinical impact curves, and subgroups based on model scores were used to determine clinical practicability. The area under the curve of the LNM and DM nomograms were 0.668 and 0.807, respectively. The corresponding C-index of OS nomogram was 0.752. Calibration curves and DCA showed an effective predictive accuracy and clinical applicability. In patients with T1N0M0 EC, surgery alone (p < 0.01) proved a survival advantage. Chemotherapy and radiotherapy indicated a better prognosis in the subgroup analysis for T1 EC patients with LNM or DM. We created three nomograms to predict the likelihood of LNM, DM, and OS probability in patients with early EC using a generalizable dataset. These useful visual tools could help clinical physicians deliver appropriate perioperative care.

Early Readout on Overall Survival of Patients With Melanoma Treated With Immunotherapy Using a Novel Imaging Analysis

Existing criteria to estimate the benefit of a therapy in patients with cancer rely almost exclusively on tumor size, an approach that was not designed to estimate survival benefit and is challenged by the unique properties of immunotherapy. More accurate prediction of survival by treatment could enhance treatment decisions. To validate, using radiomics and machine learning, the performance of a signature of quantitative computed tomography (CT) imaging features for estimating overall survival (OS) in patients with advanced melanoma treated with immunotherapy. This prognostic study used radiomics and machine learning to retrospectively analyze CT images obtained at baseline and first follow-up and their associated clinical metadata. Data were prospectively collected in the KEYNOTE-002 (Study of Pembrolizumab [MK-3475] Versus Chemotherapy in Participants With Advanced Melanoma; 2017 analysis) and KEYNOTE-006 (Study to Evaluate the Safety and Efficacy of Two Different Dosing Schedules of Pembrolizumab [MK-3475] Compared to Ipilimumab in Participants With Advanced Melanoma; 2016 analysis) multicenter clinical trials. Participants included 575 patients with a diagnosis of advanced melanoma who were randomly assigned to training and validation sets. Data for the present study were collected from November 20, 2012, to June 3, 2019, and analyzed from July 1, 2019, to September 15, 2021. KEYNOTE-002 featured trial groups testing intravenous pembrolizumab, 2 mg/kg or 10 mg/kg every 2 or every 3 weeks based on randomization, or investigator-choice chemotherapy; KEYNOTE-006 featured trial groups testing intravenous ipilimumab, 3 mg/kg every 3 weeks and intravenous pembrolizumab, 10 mg/kg every 2 or 3 weeks based on randomization. The performance of the signature CT imaging features for estimating OS at the month 6 posttreatment landmark in patients who received pembrolizumab was measured using an area under the time-dependent receiver operating characteristics curve (AUC). A random forest model combined 25 imaging features extracted from tumors segmented on CT images to identify the combination (signature) that best estimated OS with pembrolizumab in 575 patients. The signature combined 4 imaging features, 2 related to tumor size and 2 reflecting changes in tumor imaging phenotype. In the validation set (287 patients treated with pembrolizumab), the signature reached an AUC for estimation of OS status of 0.92 (95% CI, 0.89-0.95). The standard method, Response Evaluation Criteria in Solid Tumors 1.1, achieved an AUC of 0.80 (95% CI, 0.75-0.84) and classified tumor outcomes as partial or complete response (93 of 287 [32.4%]), stable disease (90 of 287 [31.3%]), or progressive disease (104 of 287 [36.2%]). The findings of this prognostic study suggest that the radiomic signature discerned from conventional CT images at baseline and on first follow-up may be used in clinical settings to provide an accurate early readout of future OS probability in patients with melanoma treated with single-agent programmed cell death 1 blockade.

The Role of Critical N6-Methyladenosine-Related Long Non-Coding RNAs and Their Correlations with Immune Checkpoints in Renal Clear Cell Carcinoma

PurposeThis study aimed to evaluate the functions of critical N6-methyladenosine (m6A)-related long non-coding RNAs (lncRNAs) and their correlations with immunotherapeutic targets in clear cell renal cell carcinoma (ccRCC).Methodsm6A-related lncRNAs were analyzed using the dataset from The Cancer Genome Atlas database via Pearson correlation analysis. Then, their prognostic functions in patients with ccRCC were determined via univariate Cox analysis. A prognostic m6A-related lncRNA signature (MRLS) in ccRCC was established using the least absolute shrinkage and selection operator (LASSO) Cox regression model. In addition, the correlations between these prognostic m6A-related lncRNAs with immune checkpoints were further evaluated in clinical samples.ResultsMRLS was established by the LASSO Cox regression model on the basis of seven prognostic m6A-related lncRNAs. The risk score for each patient was calculated using the MRLS model, and the patients were further stratified into high- and low-risk subgroups. The MRLS model was validated with a robust prognostic ability by the stratification analysis. On the basis of age, grade, stage, and risk score, a nomogram was developed with a strong reliability in forecasting the overall survival percentages of the patients with ccRCC. Moreover, seven prognostic m6A-related lncRNAs enrolled in the MRLS model were found to be correlated with various immunotherapeutic targets, namely, PD-1, PD-L1, CTLA4, and LAG3, and the expression levels of which in the high-risk subgroup were significantly higher than those in the low-risk subgroup. The significant correlations between LINC00342 and the aforementioned immunotherapeutic targets were also confirmed in clinical samples.ConclusionIn this study, seven m6A-related lncRNAs were identified as potential biomarkers for forecasting the prognosis of patients with ccRCC and evaluating the efficacy of immunotherapy for these patients. Furthermore, a prognostic and predictive MRLS model with a high reliability was constructed to predict the overall survival probability of patients with ccRCC.

Discontinuation of anti-PD-1 monotherapy in advanced melanoma-Outcomes of daily clinical practice.

There is no consensus on the optimal treatment duration of anti‐PD‐1 for advanced melanoma. The aim of our study was to gain insight into the outcomes of anti‐PD‐1 discontinuation, the association of treatment duration with progression and anti‐PD‐1 re‐treatment in relapsing patients. Analyses were performed on advanced melanoma patients in the Netherlands who discontinued first‐line anti‐PD‐1 monotherapy in the absence of progressive disease (n = 324). Survival was estimated after anti‐PD‐1 discontinuation and with a Cox model the association of treatment duration with progression was assessed. At the time of anti‐PD‐1 discontinuation, 90 (28%) patients had a complete response (CR), 190 (59%) a partial response (PR) and 44 (14%) stable disease (SD). Median treatment duration for patients with CR, PR and SD was 11.2, 11.5 and 7.2 months, respectively. The 24‐month progression‐free survival and overall survival probabilities for patients with a CR, PR and SD were, respectively, 64% and 88%, 53% and 82%, 31% and 64%. Survival outcomes of patients with a PR and CR were similar when anti‐PD‐1 discontinuation was not due to adverse events. Having a PR at anti‐PD‐1 discontinuation and longer time to first response were associated with progression [hazard ratio (HR) = 1.81 (95% confidence interval, CI = 1.11‐2.97) and HR = 1.10 (95% CI = 1.02‐1.19; per month increase)]. In 17 of the 27 anti‐PD‐1 re‐treated patients (63%), a response was observed. Advanced melanoma patients can have durable remissions after (elective) anti‐PD‐1 discontinuation.

A New Clinical Nomogram From the TCGA Database to Predict the Prognosis of Hepatocellular Carcinoma.

Background and AimHepatocellular carcinoma is a common malignant tumor of the digestive system with a poor prognosis. The high recurrence rate and metastasis after surgery reduce the survival time of patients. Therefore, assessing the overall survival of patients with hepatocellular carcinoma after hepatectomy is critical to clinicians’ clinical decision-making. Conventional hepatocellular carcinoma assessment systems (such as tumor lymph node metastasis and Barcelona clinical hepatocellular carcinoma) are obviously insufficient in assessing the overall survival rate of patients. This research is devoted to the development of nomogram assessment tools to assess the overall survival probability of patients undergoing liver resection.MethodsWe collected the clinical and pathological information of 438 hepatocellular carcinoma patients undergoing surgery from The Cancer Genome Atlas (TCGA) database, then excluded 87 patients who did not meet inclusion criteria. Univariate and multivariate analyses were performed on patient characteristics and related pathological factors. Finally, we developed a nomogram model to predict patient’s prognosis.ResultsA retrospective analysis of 438 consecutive samples from the TCGA database of patients with hepatocellular carcinoma who underwent potentially curative liver resections. Six risk factors were included in the final model. In the training set, the discriminative ability of the nomogram was very good (concordance index = 0.944), and the external verification method (concordance index = 0.962) was used for verification. At the same time, the internal and external calibration of the model was verified, showing that the model was well calibrated. The calibration between the evaluation of the nomogram and the actual observations was good. According to the patient’s risk factors, we determined the patient’s Kaplan-Meyer survival analysis curve. Finally, the clinical decision curve was used to compare the benefits of two different models in evaluating patients’ clinical outcomes.ConclusionsThe nomogram can be used to evaluate the post-hepatectomy 1-, 3-, and 5-year survival rates of patients with hepatocellular carcinoma. The Kaplan-Meyer curve can intuitively display the survival differences among patients with various risk factors. The clinical decision curve is a good reference guide for clinical application.

STAT3 Mediated miR-30a-5p Inhibition Enhances Proliferation and Inhibits Apoptosis in Colorectal Cancer Cells

Signal transducer and activator of transcription 3 (STAT3), a transcriptional factor involved in tumorigenesis and cancer stemness formation, contributes to drug resistance in cancer therapies. STAT3 not only mediates gene transcription but also participates in microRNA suppression. This study identified a STAT3-downstream micro RNA (miRNA) involved in drug resistance against regorafenib in colorectal cancer stem-like tumorspheres. Small RNAseq was used to investigate differential microRNAs in colorectal cancer cell-derived tumorspheres and in a STAT3-knockdown strain. The miRNA-mediated genes were identified by comparing RNAseq data with gene targets predicted using TargetScan. Assays for detecting cell viability and apoptosis were used to validate findings. The formation of colorectal cancer stem-like tumorspheres was inhibited by BBI608, a STAT3 inhibitor, but not by regorafenib. Additional investigations for microRNA expression demonstrated an increase in 10 miRNAs and a decrease in 13 miRNAs in HT29-derived tumorspheres. A comparison of small RNAseq results between tumorspheres and HT29shSTAT3 cells revealed the presence of four STAT3-mediated miRNAs in HT29-derived tumorspheres: hsa-miR-215-5p, hsa-miR-4521, and hsa-miR-215-3p were upregulated, whereas miR-30a-5p was downregulated. Furthermore, hsa-miR-4521 was associated with poor overall survival probability, and miR-30a-5p was associated with better overall survival probability in patients with rectum cancer. Comparisons of RNAseq findings between HCT116- and HT29-derived tumorspheres revealed that HSPA5 were mediated by the STAT3-miR-30a-5p axis, which is overexpressed in colorectal tumorspheres associating to anti-apoptosis. In addition, the transfection of miR-30a-5p and inhibition of HSPA5 by HA15 significantly reduced cell viability and increased apoptosis in HT29 cells. In conclusion, a STAT3-miR-30a-5p-HSPA5 axis was observed against regorafenib-mediated apoptosis in colorectal cancer tumorspheres. The expression of miR-30a-5p was repressed by STAT3; in addition, HSPA5 was identified as the target gene of miR-30a-5p and contributed to both tumorsphere formation and anti-apoptosis.

Calculating the overall survival probability in patients with cervical cancer: a nomogram and decision curve analysis-based study

BackgroundCervical cancer has long been a common malignance troubling women. However, there are few studies developing nomogram with comprehensive factors for the prognosis of cervical cancer. Hence, we aimed to build a nomogram to calculate the overall survival (OS) probability in patients with cervical cancer.MethodsData of 9876 female patients in SEER database and diagnosed as cervical cancer during 2010–2015, was retrospectively analyzed. Univariate and multivariate Cox proportional hazard regression model were applied to select predicted factors and a nomogram was developed to visualize the prediction model. The nomogram was compared with the FIGO stage prediction model. Harrell’s C-index, receiver operating curve, calibration plot and decision curve analysis were used to assess the discrimination, accuracy, calibration and clinical utility of the prediction models.ResultEleven independent prognostic variables, including age at diagnosis, race, marital status at diagnosis, grade, histology, tumor size, FIGO stage, primary site surgery, regional lymph node surgery, radiotherapy and chemotherapy, were used to build the nomogram. The C-index of the nomogram was 0.826 (95% CI: 0.818 to 0.834), which was better than that of the FIGO stage prediction model (C-index: 0.785, 95% CI: 0.776 to 0.793). Calibration plot of the nomogram was well fitted in 3-year overall OS prediction, but overfitting in 5-year OS prediction. The net benefit of the nomogram was higher than the FIGO prediction model.ConclusionA clinical useful nomogram for calculating the overall survival probability in cervical cancer patients was developed. It performed better than the FIGO stage prediction model and could help clinicians to choose optimal treatments and precisely predict prognosis in clinical care and research.

Score for the Overall Survival Probability of Patients With Pancreatic Adenocarcinoma of the Body and Tail After Surgery: A Novel Nomogram-Based Risk Assessment.

Pancreatic adenocarcinoma of the body and tail often has a dismal prognosis and lacks a specific prognostic stage. The aim of this study was to construct a nomogram for predicting survival of patients with pancreatic adenocarcinoma of the body and tail after surgery. Data of patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database and from medical records of Sun Yat-sen University Cancer Center (SYSUCC). In a multivariate analysis for overall survival (OS), the following six variables were identified as independent predictors and incorporated into the nomogram: age, tumor differentiation, tumor size, lymph node ratio (LNR), and chemotherapy. A nomogram was built based on independent risk predictors. The concordance index (C-index) for nomogram, Tumor-Node-Metastasis (TNM) 7th and 8th stage system were 0.775 [95% confidence interval (CI), 0.731–0.819], 0.617 (95%CI, 0.575–0.659), and 0.632 (95%CI, 0.588–0.676), respectively. The calibrated nomogram predicted survival rates which closely corresponded to the actual survival rates. Furthermore, the values of the area under receiver operating characteristic (ROC) curves (AUC) of the nomograms were higher than those of the TNM 7th or 8th stage system in predicting 1-, 2-, and 3-year survival of patients in training and external validation cohorts. The well-calibrated nomogram could be used to predict prognosis for patients with pancreatic adenocarcinoma of the body and tail after surgery.

A new tool for comprehensive geriatric assessment in elderly patients with acute myeloid leukemia: a pilot study from China.

Background:Acute myeloid leukemia (AML) is a common type of hematological malignancy in elderly people. Geriatricians have developed comprehensive geriatric assessment (CGA) methods for elderly patients; however, the tools used for CGA in AML are not uniform. Thus, we aimed to validate the instrumental activities of daily living (IADL) scales, age, comorbidities (Charlson Comorbidity Index), and albumin (IACA) index, which is a new tool for CGA, in elderly patients with AML.Methods:Patients aged ≥60 years who had been diagnosed with AML were screened for eligibility. Among the IACA low-, intermediate-, and high-risk groups, continuous variables were compared using the Mann-Whitney U test, and categorical variables were compared using χ2 and Fisher exact tests. In addition, probabilities of overall survival (OS) were estimated using the Kaplan-Meier method.Results:A total of 21, 34, and 6 patients were categorized into IACA low-risk (0 point), intermediate-risk (1–2 points), and high-risk (≥3 points) groups, respectively. The rates of relapse/progression-related mortality were 23.8%, 58.8%, and 100.0% in the IACA low-, intermediate-, and high-risk groups, respectively (χ2 = 12.81, P < 0.001). The 2-year probabilities of OS were 47.7% (95% confidence interval [CI] 22.8%–72.6%) and 20.2% (95% CI 5.9%–34.5%) in the IACA low- and intermediate-risk groups, respectively (χ2 = 5.99, P = 0.014), which were significantly higher than those in the high-risk group (low-risk [47.7% (95% CI 22.8%–72.6%)] vs. high-risk [0], χ2 = 20.80, P < 0.001; intermediate-risk [20.2% (95% CI 5.9%–34.5%)] vs. high-risk [0], χ2 = 7.56, P = 0.006; respectively). In the IACA low-risk group, the 2-year probability of OS in patients receiving induction chemotherapy (50.8% [95% CI 24.1%–77.5%]) was significantly higher than that in those receiving best supportive care (0, χ2 = 25.74, P < 0.001).Conclusion:We suggest that the IACA index might be a simple and effective tool for comprehensive geriatric assessment in elderly AML patients.

CLONE OF PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA AND OTHER PREDICTORS OF THE RESPONSE TO IMMUNOSUPPRESSIVE THERAPY IN PATIENTS WITH IDIOPATHIC APLASTIC ANAEMIA

Introduction. The pathogenesis of acquired aplastic anaemia (AA) is based on immune-mediated development of bone marrow failure. The absence of clear reasons for the development of immune aggression determines the relevance of investigations aimed at studying genetic disorders in the remaining pool of hematopoietic stem cells, in the hematopoietic niche, as well as mechanisms underlying the failure of immunological tolerance.Aim. The present literature review describes the most relevant markers used for characterising AA patients on the basis of their possible response to immunosuppressive therapy (IT) and for forming groups being at risk of developing refractoriness and clonal evolution.General findings. The overall survival probability in patients with AA following program IT is comparable to the results of transplanting allogeneic hematopoietic blood stem cells (allo-HSCT) from a related donor in the first line of therapy. According to current Russian and international recommendations, the tactics for treating AA patients is determined by the patient’s age and the presence of an HLA-identical sibling. Allo-HSCT from a related HLA-identical donor is a method used for treating patients younger than 40 years; however, the possibility of performing allo-HSCT is limited by donor availability. Although the event-free survival probability during IT is inferior to the results of allo-HSCT, IT remains the main treatment method for most patients with AA. In order to minimise adverse outcomes, it is necessary to consider predictors of treatment efficacy along with the likelihood of developing late clonal evolution as early as at the AA diagnosis stage. Patient evaluation and formation of risk groups will facilitate selection of the most optimal treatment approach at the therapy planning stage, which includes either IT combination with thrombopoietin receptor agonists, or a search for an unrelated HLA-compatible donor and timely allo-HSCT.

Score for the Overall Survival Probability of Patients With First-Diagnosed Distantly Metastatic Cervical Cancer: A Novel Nomogram-Based Risk Assessment System.

Background: Metastatic cervical cancer (mCEC) is the end stage of cervical cancer. This study aimed to establish and validate a nomogram to predict the overall survival (OS) of mCEC patients.Methods: We investigated the Surveillance, Epidemiology, and End Results (SEER) database for mCEC patients diagnosed between 2010 and 2014. Univariate and multivariable Cox analyses was performed to select the clinically important predictors of OS when developing the nomogram. The performance of nomogram was validated with Harrell's concordance index (C-index), calibration curves, receiver operating characteristic curve (ROC), and decision curve analysis (DCA).Results: One thousand two hundred and fifty-two mCEC patients were included and were divided into training (n = 880) and independent validation (n = 372) cohorts. Age, race, pathological type, histology grade, radiotherapy, and chemotherapy were independent predictors of OS and used to develop the nomogram for predicting 1- and 3-year OS. This nomogram had a C-index of 0.753 (95% confidence interval [CI]: 0.780–0.726) and 0.751 (95% CI: 0.794–0.708) in the training and the validation cohorts, respectively. Internal and external calibration curves indicated satisfactory agreement between nomogram prediction and actual survival, and DCA indicated its clinical usefulness. Furthermore, a risk stratification system was established that was able to accurately stratify mCEC patients into three risk subgroups with significantly different prognosis.Conclusions: We constructed the first nomogram and corresponding risk classification system to predict the OS of mCEC patients. These tools showed satisfactory accuracy, and clinical utility, and could aid in patient counseling and individualized clinical decision-making.

Survival of AML Patients Relapsing after Hematopoetic Stem Cell Transplantation: A Single Center Experience

Although it is presumed to be a curative strategy for intermediate and high risk acute myeloid leukemia (AML), many patients relapse after allogeneic hematopoietic stem cell transplantation. This prompt us to examine the ways to improve the outcomes. We retrospectively evaluated 76 AML patients who were transplanted between 2007-2017 years in our clinic. We tried to identify the factors associated with posttransplant relapse, postrelapse survival and if there was a survival benefit of pretransplant consolidation and minimal residual disease (MRD) negativity. We examined the effect of the acute-chronic graft versus host disease (GVHD) and salvage therapy after the posttransplant relapses. The mean age of the patients was 44.6±1.21 years (ranges 21-67). 42.1% were females and 57.9% were males. 43.3% of the patients were in complete remission (CR) MRD positive state before the transplantation whereas 35.5% were in CR MRD negative and 3.9% were in progressive disease state. In 13 patients who were in CR state, the MRD status were not known. 11 (14.5%) patients were considered as in favorable risk, 52 (68.4%) in intermediate risk and 13 (17.1%) in unfavorable risk with respect to cytogenetic analysis before the transplantation. The donors were HLA compatible relatives (77.6%), HLA compatible non-relatives (10.5%), haploidentical people (9.2%), one HLA incompatible relative (1.3%) and one HLA incompatible nonrelative (1.3%). 74 bone marrow transplantations (97.4%) were allogeneic and the remaining two (2.6%) were autologous. Myeloablative conditioning regimen was applied to 57 patients (75%) and 19 patients got (25%) reduced intensity conditioning regimen. GVHD developed in 51.3% after transplantation and 61.5% of these were chronic extensive. Relapse occurred in 27 patients (35.5%), hematological relapse being the most common (31.6%). The median time for the development of relapse was found to be 5.5 months (range: 1.5-37). The overall probability for the development of a relapse was found to be 48.7% (95% CI: 40.9-56.5)(Figure1A). 23 patients (30.3%) died during the study period with a median survival of 9.6 months (range: 1.6-45). In the studied population the overall survival probability was found to be 52.8% (95% CI: 45.4 - 60.2) [Figure 1B]. 36.4%, 28.8% and 30.8% of the patients with favorable, intermediate and unfavorable cytogenetic status died respectively during the study period. The comparison of the survival probability of the patients with favorable, intermediate and unfavorable cytogenetic status was depicted in Figure 2. The overall survival probability of the patients with favorable, intermediate and unfavorable cytogenetic status were 46.6% (95% CI: 26.2-66.9), 54.6% (95 % CI: 45.9 - 63.2) and 36.9 % (95% CI: 25.4 - 48.5) respectively (p=0.807).MRD status of 60 patients were known. At the end of the study period 75.8% of the CR MRD positive and 70.4% of the CR MRD negative patients remained alive. The comparison of the survival of patients in CR with respect to MRD status is shown in Figure 3. The overall survival probability of CR MRD positive patients was 56.3 % (95% CI: 45.3 - 67.3) and this rate was 52.5 % (95% CI: 40.8 - 64.3) in MRD negative patients (p=0.770) [Figure 3].Patients who developed GVHD had similar overall survival probability with the patients who did not developed the disease; 47.0% vs 57.2%, p=0.115 (Figure 4A). Even the patients with chronic extensive GVHD had similar overall survival rates with the patients who had none or acute GVHD; 49.3 % vs 58.2%, p=0.27 (Figure 4B).66.7% of the patients with a progressive disease before the transplantation died during the study period and this rate was 27.1% in the patients with CR (p=0.005).In conclusion the overall survival rate of the transplanted AML patients was 52.8% in the study group. The overall survival did not seem to be affected by pre-transplant MRD status, cytogenetic risk factors and administration of consolidation therapy. The only patients who had significantly worse results were the ones who had progressive disease before the transplantation. From this point it would be logical to make transplantation whenever the patient is in first CR regardless of the MRD status and a matched donor is found so that the toxic effects of the consolidation chemotherapy may be prevented. DisclosuresNo relevant conflicts of interest to declare.

The Role of Neutrophil Extracellular Traps in Cancer-Associated Arterial Thrombosis

Introduction: Prior studies have indicated that Neutrophil extracellular traps (NETs) trigger arterial thromboembolism (ATE) and play a role in the pathogenesis of cancer-associated venous thrombosis. We investigated the association between NET biomarkers (citrullinated histone H3 [H3Cit], cell-free DNA [cfDNA], and nucleosomes) and the risk of ATE in patients with cancer.Methods: In this prospective cohort study, H3Cit, cfDNA and nucleosome levels were determined at study inclusion, and patients with newly diagnosed cancer or progressive disease after remission were followed for 2 years for objectively confirmed, symptomatic ATE and death. Fine&Gray competing-risk regression was used to model risk of ATE. Overall survival (OS) was analyzed with Kaplan-Meier estimators.Results: Nine-hundred and fifty-eight patients with cancer (median age: 61 years; 46.8% female; Table 1) were recruited. ATE occurred in 22 patients; the cumulative 6-, 12-, and 24-month risks of ATE were 1.1%, 1.8%, and 2.3%, respectively. The subdistribution hazard ratios (SHR) for ATE of H3Cit, cfDNA, and nucleosomes per unit increase were 1.0 (95% confidence interval [CI]: 1.0-1.0, p=.882), 1.0 (1.0-1.0, p=.639), and 1.1 (1.0-1.2, p=.246) respectively. The 6-, 12-, and 24-month ATE probability was 1.3%, 1.7%, and 2.6% in patients with a H3Cit level ≤ 75thpercentile, and 0.8%, 1.3%, and 1.7% in patients above this cut-off (SHR=0.7, 0.2-2.0, p=.460).The 6-, 12-, 24-month overall survival of the study cohort was 87.0% (95%CI: 84.6-89.0), 73.6% (70.6-76.3), and 57.6% (54.3-60.8), respectively. The hazard ratio (HR) for mortality of H3Cit, cfDNA, and nucleosomes per unit increase were 1.0 (1.0-1.0, p<.001), 1.0 (1.0-1.0, p<.001), and 1.0 (1.0-1.1, p=.181) respectively. For better illustration we defined two groups of patients with elevated or non-elevated NET biomarkers. Therefore, we set an empiric cut-off at the 75thpercentile of the study cohort. Elevated H3Cit (HR=1.7, 1.3-2.1, p<.001), and cfDNA levels (HR=1.4, 1.1-1.7, p=.008) were associated with an increased risk of mortality after adjusting for age, and sex (Figure 1A&B). No association was found between higher nucleosome levels and the risk of all-cause mortality in patients with cancer (HR=1.2, 1.0-1.5, p=.088, Figure 1C).Conclusion: There was no significant association between H3Cit, cfDNA, and nucleosomes and ATE occurrence in patients with cancer. However, elevated levels of H3Cit, and cfDNA, were independently associated with an increased risk of mortality in patients with cancer.Table 1.Baseline characteristics of the total study population. Continuous data is reported as medians with first and third quartiles. Categorical variables are given as absolute frequencies and percentages. Data on body mass index, and cancer stage are missing in 2, and 76 patients, respectively. aPatients with brain and hematologic cancerFigure 1.Kaplan-Meier estimated for overall survival probability of patients with cancer according to baseline H3Cit, cfDNA, and nucleosome levels. MoM = Multiple-of-the-mean (i.e. Nucleosome results were compared to pooled plasma from 5 young male healthy controls to obtain a multiple-of-the-median) [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

CAMKs support development of acute myeloid leukemia

BackgroundWe recently identified the human leukocyte immunoglobulin-like receptor B2 (LILRB2) and its mouse ortholog-paired Ig-like receptor (PirB) as receptors for several angiopoietin-like proteins (Angptls). We also demonstrated that PirB is important for the development of acute myeloid leukemia (AML), but exactly how an inhibitory receptor such as PirB can support cancer development is intriguing.ResultsHere, we showed that the activation of Ca (2+)/calmodulin-dependent protein kinases (CAMKs) is coupled with PirB signaling in AML cells. High expression of CAMKs is associated with a poor overall survival probability in patients with AML. Knockdown of CAMKI or CAMKIV decreased human acute leukemia development in vitro and in vivo. Mouse AML cells that are defective in PirB signaling had decreased activation of CAMKs, and the forced expression of CAMK partially rescued the PirB-defective phenotype in the MLL-AF9 AML mouse model. The inhibition of CAMK kinase activity or deletion of CAMKIV significantly slowed AML development and decreased the AML stem cell activity. We also found that CAMKIV acts through the phosphorylation of one of its well-known target (CREB) in AML cells.ConclusionCAMKs are essential for the growth of human and mouse AML. The inhibition of CAMK signaling may become an effective strategy for treating leukemia.

Changes in treatment patterns for patients with locally advanced rectal cancer in the United States over the past decade: An analysis from the National Cancer Data Base (NCDB).

691 Background: Neoadjuvant chemoradiation therapy (NACRT) is widely accepted as the standard of care for treatment of locally advanced rectal cancer in the United States. We sought to examine patterns of treatment for locally advanced rectal cancer in US over the past decade. Methods: Using the National Cancer Data Base (NCDB), we identified 66,197 patients diagnosed with stage II-III rectal adenocarcinoma and treated between 2004 and 2012. We described trends in receipt of treatment based on aggregated data for three time periods (2004-2006, 2007-2009, 2010-2012), using trend test. We analyzed 5-yr overall survival (OS) probabilities for 28,550 patients treated between 2004 and 2007. Results: Receipt of NACRT increased significantly over the past decade from 42.9% in 2004-2006 to 50.0% in 2007-2009, and then to 55.0% in 2010-2012 (p &lt; 0.0001). In contrast, use of adjuvant chemoradiation (CRT) decreased steadily from 16.7% in 2004-2006 to 10.5% in 2007-2009, and then to 6.7% in 2010-2012 (p &lt; 0.0001). Similarly, treatment with surgery alone decreased from 13.1% in 2004-2006 to 8.7% in 2010-2012 (p &lt; 0.0001). Older age, presence of comorbidities, larger primary tumor size, lymph node involvement, non-Hispanic white ethnicity, lack of private insurance, and being treated at a non-high case volume facility were associated with a significantly lower chance of receiving NACRT in multivariable logistic regression analysis. 5-yr OS probabilities for patients treated with NACRT, surgery and adjuvant CRT, surgery alone, and definitive CRT were 72.4%, 70.9%, 44.9% and 48.8%, respectively. Conclusions: Utilization of NACRT prior to surgery in US patients diagnosed with locally advanced rectal cancer has substantially increased over the past decade. However, only about half of these patients currently receive the standard therapy as recommended by national guidelines, and there may be social and economic barriers to receiving the standard of care. Tri-modality therapy is associated with the best outcomes for these patients, and surgery alone or definitive chemo-radiation should only be reserved for patients unable to tolerate tri-modality therapy.