Prognostic Variables For Overall Survival Research Articles

IL-17 expression and prognosis of laryngeal squamous cell carcinoma.

Objective: To investigate the roles of proinflammatory cytokine IL-17 in the prognosis of laryngeal squamous cell carcinoma (LSCC). Methods: In all, 67 LSCC patients were enrolled to evaluate the expression of IL-17, IL-23, CD8, CD31, and vascular endothelial growth factor by immunohistochemical staining. Cumulative survival time was determined by the Kaplan-Meier approach, and prognostic variables for overall survival (OS) were identified by Cox proportional-hazards models. Results: The expression of IL-17 and IL-23 was remarkably higher in LSCC tissue than in adjacent normal (AN) tissue (P < .001). The Kaplan-Meier analysis indicated that patients with cervical lymph node metastasis (CLNM), advanced tumor node metastasis (TNM) stage, poor-differentiated grade, high microvessel density (MVD) in LSCC tissues, and high IL-17 expression in AN tissues had poorer OS (all P < .05). Cox regression analysis revealed that CLNM (HR = 7.246; 95% CI: 2.598-20.208; P < .001), high MVD in tumor tissues (HR = 4.233; 95% CI: 1.482-12.092; P = .007), and low CD8 expression in AN tissues (HR = 3.996; 95% CI: 1.442-11.074; P = .008) were significantly associated with poorer OS in LSCC, while IL-17 expression in AN tissue was not. Conclusion: High IL-17 expression in AN tissues could indicate poor prognosis and may be a prognostic marker for LSCC. Low CD8 expression in AN tissues may represent poor frontline antitumor immunity and be associated with poor prognosis.

EGFR is a potential therapeutic target for highly glycosylated and aggressive pancreatic neuroendocrine neoplasms.

pNENs are relative indolent tumors with heterogeneous clinical presentation at diagnosis. It is important to establish aggressive subgroups of pNENs and identify potential therapeutic targets. Patients with pNEN (322 cases) were included to examine the association between glycosylation biomarkers and clinical/pathological traits. The molecular and metabolic features stratified by glycosylation status were assessed by RNA-seq/whole exome sequencing and immunohistochemistry. A considerable proportion of patients had elevated glycosylation biomarkers (carbohydrate antigen [CA] 19-9, 11.9%; CA125, 7.5%; carcinoembryonic antigen [CEA], 12.8%). CA19-9 (hazard ratio [HR]=2.26, P=.019), CA125 (HR=3.79, P=.004) and CEA (HR=3.16, P=.002) were each independent prognostic variables for overall survival. High glycosylation group, defined as pNENs with elevated level of circulating CA19-9, CA125 or CEA, accounted for 23.4% of all pNENs. High glycosylation (HR=3.14, P=.001) was an independent prognostic variable for overall survival and correlated with G3 grade (P < .001), poor differentiation (P=.001), perineural invasion (P=.004) and distant metastasis (P < .001). Epidermal growth factor receptor (EGFR) was enriched in high glycosylation pNENs using RNA-seq. EGFR was expressed in 21.2% of pNENs using immunohistochemistry and associated with poor overall survival (P=.020). A clinical trial focusing on EGFR expressed pNENs was initiated (NCT05316480). Thus, pNEN with aberrant glycosylation correlates with a dismal outcome and suggests potential therapeutic target of EGFR.

Nomogram model predicting the overall survival for patients with primary gastric mucosa-associated lymphoid tissue lymphoma

Increasingly extranodal marginal B-cell lymphoma of mucosa-associated lymphoid tissue, known as mucosa-associated lymphoid tissue (MALT) lymphoma, is a type of non-Hodgkin's lymphoma. The prognosis of primary gastric MALT (GML) patients can be affected by many factors. Clinical risk factors, including age, type of therapy, sex, stage and family hematologic malignancy history, also have significant effects on the development of the disease. The available data are mainly focused on epidemiology; in contrast, few studies have investigated the prognostic variables for overall survival (OS) in patients with primary GML. Based on the realities above, we searched a large amount of data on patients diagnosed with primary GML in the Surveillance, Epidemiology and End Results (SEER) database. The aim was to develop and verify a survival nomogram model that can predict the overall survival prognosis of primary GML by combining prognostic and determinant variables. To create an effective survival nomogram for patients with primary gastric GML. All data of patients with primary GML from 2004 to 2015 were collected from the SEER database. The primary endpoint was OS. Based on the LASSO and COX regression, we created and further verified the accuracy and effectiveness of the survival nomogram model by the concordance index (C-index), calibration curve and time-dependent receiver operating characteristic (td-ROC) curves. A total of 2604 patients diagnosed with primary GML were selected for this study. A total of 1823 and 781 people were randomly distributed into the training and testing sets at a ratio of 7:3. The median follow-up of all patients was 71 mo, and the 3- and 5-year OS rates were 87.2% and 79.8%, respectively. Age, sex, race, Ann Arbor stage and radiation were independent risk factors for OS of primary GML (all P < 0.05). The C-index values of the nomogram were 0.751 (95%CI: 0.729-0.773) and 0.718 (95%CI: 0.680-0.757) in the training and testing cohorts, respectively, showing the good discrimination ability of the nomogram model. Td-ROC curves and calibration plots also indicated satisfactory predictive power and good agreement of the model. Overall, the nomogram shows favorable performance in discriminating and predicting the OS of patients with primary GML. A nomogram was developed and validated to have good survival predictive performance based on five clinical independent risk factors for OS for patients with primary GML. Nomograms are a low-cost and convenient clinical tool in assessing individualized prognosis and treatment for patients with primary GML.

Deep learning of bone metastasis in small cell lung cancer: A large sample-based study.

Bone is a common metastatic site for small cell lung cancer (SCLC). Bone metastasis (BM) in patients have are known to show poor prognostic outcomes. We explored the epidemiological characteristics of BM in SCLC patients and create a new deep learning model to predict outcomes for cancer-specific survival (CSS) and overall survival (OS). Data for SCLC patients diagnosed with or without BM from 2010 to 2016 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox proportional hazards regression models were used to evaluate the effects of prognostic variables on OS and CSS. Through integration of these variables, nomograms were created for the prediction of CSS and OS rates at 3-month,6- month,and 12-month. Harrell's coordination index, calibration curves,and time- dependent ROC curves were used to assess the nomograms' accuracy. Decision tree analysis was used to evaluate the clinical application value of the established nomogram. In this study, 4201 patients were enrolled. Male sex, tumor size 25 but <10, brain and liver metastases, as well as chemotherapy were associated with a high risk for BM. Tumor size, Age, N stage, gender, liver metastasis, radiotherapy as well as chemotherapy were shown to be prognostic variables for OS, and the prognostic variables for CSS were added to the tumor number in addition. Based on these results, nomograms for CSS and OS were established separately. Internal as well as external validation showed that the C-index, calibration cuurve and DCA had good constructive correction effect and clinical application value. Decision tree analysis further confirmed the prognostic factors of OS and CSS. The nomogram and decision tree models developed in this study effectively guided treatment decisions for SCLC patients with BM. The creation of prediction models for BM SCLC patients may be facilitated by deep learning models.

Evaluation of Prognostic Factors and Trastuzumab-based Treatments in HER2/Neu-positive Metastatic Gastric Cancer.

To determine the efficacy of trastuzumab-based treatment in patients with HER2/neu-positive metastatic gastric cancer. Observational study. Department of Medical Oncology, Istanbul University, Institute of Oncology, Istanbul, Turkey, between January 2014 and December 2020. The clinicopathological characteristic and treatment data of patients with HER2/neu-positive metastatic gastric cancer were recorded retrospectively. Kaplan-Meier analysis was performed to compare the chemotherapy regimens. Sixty-three patients were included in the study. The average age was 61. Female patients accounted for 27% of the total, while male patients accounted for 73%. De novo metastatic cases accounted for 44 (69.8%) of the total number of patients. The median survival time was 13.6 (8-19.3) months. Complete response was 6.3%, partial response was 39.7%, and the stable response was 9.5% with trastuzumab-based chemotherapy. The overall survival (p= 0.45) and progression-free survival (p=0.893) were similar for different chemotherapy regimens. The grade 1-2 to grade 3-4 toxicity ratio was 79.6% and 20.6%, respectively. The patients' performance (p<0.001) and the number of metastatic sites (p=0.001) were both shown to be unfavourable predictive variables for OS in multivariate analysis. The addition of taxane to trastuzumab-based combinations (with platinum and fluoropyrimidine) did not affect overall and progression-free survival in this research. Three or more metastatic sites and poor performance status were found as the unfavourable prognostic variables for overall survival. Gastric cancer, Trastuzumab, Chemotherapy, Prognostic factors.

Genetic Testing at Diagnosis Has Prognostic Value in Patients with Chronic Lymphocytic Leukemia including at Early Stages

Chronic lymphocytic leukemia (CLL) has a variable clinical evolution, with some patients living treatment-free for decades while others require therapy shortly after diagnosis. In a consecutive series of 217 CLL patients, molecular biomarkers with prognostic value (IGHV status, TP53 mutations, and cytogenetics), whose analysis is recommended prior to treatment start, were studied at diagnosis. Multivariate analyses identified prognostic variables for overall survival (OS) and time to first treatment (TTFT) and validated the CLL-IPI and IPS-E variables for all or early-stage patients (Rai 0–2/Binet A), respectively. Unmutated IGHV was associated with shorter OS and TTFT, even for early-stage patients. Lymphocyte count was not statistically significant for TTFT of early-stage patients in multivariate analysis. Our results validate the prognostic value of IGHV mutational status at diagnosis for OS and TTFT, including for early stages. Our findings suggest a role for molecular and mutational analysis at diagnosis in future prospective studies.

Development and Validation of a Nomogram for Predicting Overall Survival to Concurrent Chemoradiotherapy in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma.

This study aims to develop and validate a effective prognostic nomogram for locally advanced esophageal squamous cell carcinoma (LA-ESCC) patients undergoing concurrent chemoradiotherapy (CCRT). Retrospective analysis of 503 patients with LA-ESCC given CCRT in our hospital from 2009 to 2016 was conducted. Two-thirds of the patients were randomly assigned to the training set (n = 335), and one-third were assigned to the validation set (n = 168). In order to generate the nomogram, multivariate cox regression analysis was undertaken in the training set for uncovering significant prognostic variables for overall survival. The C-index and calibration plot were used to verify nomogram discrimination and calibration, respectively. Five independent prognostic variables were found and incorporated into a nomogram: age, N stage, location, tumor response, and MLR (monocyte/lymphocyte ratio). The C-indexes of the training set and the validation set were 0.730 and 0.745, respectively. The discrimination and calibration of this nomogram showed good predictive power in both sets. Conclusively, the proposed nomogram may be served as an effective tool for prognostic evaluation of LA-ESCC patients receiving CCRT.

Comparative outcomes of pancreatic neuroendocrine neoplasms: A population-based analysis of the SEER database

BackgroundA paucity of data exists regarding the natural history and survival outcomes of pancreatic neuroendocrine neoplasms (PanNENs), a rare histological subtype which can be classified as functional (F-PanNENs) and non-functional (NF-PanNENs). The purpose of this study is to characterize their clinicopathological features and survival outcomes in a large cohort of patients from United States. MethodsAll patients diagnosed with F-PanNENs or NF-PanNENs between 1998 and 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Patient demographic, clinicopathological features and survival outcomes were analyzed. Logistic regression analysis was used to identify factors associated with NF-PanNENs diagnosis over F-PanNENs. Cox regression analysis was utilized to determine the prognostic variables for overall survival (OS) in all PanNENs patients. ResultsA total of 2347 patients were identified: 1181 in the F-PanNENs group and 1206 in the NF-PanNENs group. NF-PanNENs were larger in size, poorly differentiated, more commonly found in a head pancreas location, and had increased lymph node positivity and liver involvement compared to F-PanNENs. Patients with F-PanNENs were associated better survival outcomes than those with NF-PanNENs. Diagnosis at early year, poorer differentiation, and larger tumor size were independently correlated with NF-PanNENs diagnosis. In addition, multivariable analysis determined that age, gender, year of diagnosis, marital status, tumor grade, size, stage, number, and surgical treatment were independent prognostic factors for OS of all PanNENs patients. ConclusionThe clinicopathological characteristics and survival outcomes were significantly different between NF-PanNENs and F-PanNENs. Furthermore, we identified the clinical features correlated with NF-PanNENs diagnosis over F-PanNENs.

The Prognostic Value of Sarcopenia in Acute Myeloid Leukemia Patients and the Development and Validation of a Novel Nomogram for Predicting Survival.

BackgroundAcute myeloid leukemia (AML) occurs frequently in the elderly, of whom the prognosis is dismal. Sarcopenia is a progressive and generalized skeletal muscle disorder associated with an increased possibility of adverse outcomes. This study aims to explore the prognostic value of sarcopenia in AML patients and develop a novel prognostic model.MethodsA total of 227 AML patients were enrolled. Body composition was assessed by bioelectrical impedance analysis before treatment. Sarcopenia was diagnosed by low muscle quantity. Cox proportional hazard regression model were applied to verify prognostic variables for overall survival (OS) and disease-free survival (DFS). A novel prognostic model of nomogram was developed and validated by ‘R’.ResultsForty-one (18.1%) patients were defined as sarcopenia. The median age of the sarcopenic group was significantly greater than the non-sarcopenic group (median 70 vs. 64 years, P = 0.001). Sarcopenic patients showed significantly less height (P = 0.002), weight (P <0.001), Body Mass Index (P <0.001), Fat Mass (P = 0.017), Fat-free Mass (P <0.001), Appendicular Skeletal Muscle Mass (P <0.001), Skeletal Muscle Index (P <0.001), Fat-free Mass Index (P <0.001), and hemoglobin level (P = 0.025) than the non-sarcopenic ones. Patients in the sarcopenic group also showed a statistically shorter OS and DFS (median OS: 13.7 vs. 55.6 months, P = 0.003; median DFS: 12.5 months vs. not reached, P = 0.026). ELN high risk [Hazard Ratio (HR): 1.904, 95% Confidence Interval (CI): 1.018–3.562, P = 0.044), sarcopenia (HR: 1.887, 95% CI: 1.071–3.324, P = 0.028), and reduced-intensity regimens (HR: 3.765, 95% CI: 1.092–12.980, P = 0.036) were independent predictors for OS in multivariate analysis. A nomogram for predicting OS was constructed using the above three factors. The c index, calibration plots and decision curve analyses (DCA) showed better discrimination, calibration, and net benefits of the nomogram than the ELN model.ConclusionSarcopenia was common and had an inferior prognosis in AML and needs more attention in clinical practice.

Is breast conservation superior to mastectomy in early stage triple negative breast cancer?

PurposeCompare overall survival (OS) and breast cancer-specific survival (BCSS) outcomes of breast conservative therapy (BCT) and mastectomy in a large cohort of patients with early-stage triple negative breast cancer (TNBC), using a propensity score-based matching approach.MethodsSurveillance, Epidemiology, and End Results (SEER) database was used to study the role of RT in early stage TNBC. Primary end points were OS and BCSS. Cox proportional hazard regression models and Kaplan-Meier plots were used to generate the desired outcomes. Propensity score matching was done to minimize bias.Results12,761 patients with T1-2N0M0 TNBC as their first malignancy were retrieved. Of these 7237 had lumpectomy with RT, and 5524 had mastectomy only. Age, race, marital status, tumor laterality, grade and stage, and receipt of chemotherapy were prognostic variables for OS and BCSS. Among 4848 matched subjects, the 5-year OS was significantly higher in patients with lumpectomy and RT (89%) compared to mastectomy alone (84.5%) (p-value <0.001). Similarly, BCSS was significantly higher in patients with lumpectomy and RT (93%) compared to mastectomy alone (91%) (p-value <0.001). On subgroup analysis, patients who are younger than 40 had similar survival outcomes after either mastectomy alone or lumpectomy with RT. However, those who are older than 60, have any grade or T stage had better survival outcomes with lumpectomy and RT.ConclusionsOverall, lumpectomy followed by RT is associated with better OS and BCSS compared to mastectomy in T1-2N0M0 TNBC patients. Further research is needed to determine the optimal treatment strategy for specific patient subgroups.

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.

Prognostic Impact of NPM1/FLT3-ITD genotypes from Randomized Patients with Acute Myeloid Leukemia (AML) Treated within the International Ratify Study

Prognostic Impact of NPM1/FLT3-ITD genotypes from Randomized Patients with Acute Myeloid Leukemia (AML) Treated within the International Ratify Study

Prognostic Factors for Survival in Patients with Malignant Giant Cell Tumor of Bone: A Risk Nomogram Analysis Based on the Population.

BackgroundMalignant giant cell tumor of bone (MGCTB) is a rare histological type of malignant tumor that has a high tendency for local relapse and distant metastasis and ultimately leads to a poor prognosis. The purpose of this study was to describe the epidemiological features, identify the prognostic factors, and construct nomograms for patients with MGCTB.Material/MethodsPatients with MGCTB that was histologically diagnosed between 1973 and 2014 were selected from the Surveillance, Epidemiology, and End Results (SEER) database as a training set. Survival analysis, Lasso regression, and random forests were used to identify the prognostic variables and establish the nomograms for patients with MGCTB, while an external cohort of 37 patients from our own institution and an external cohort of 163 patients from the SEER database in 2016 were used to validate the generalization performance of the nomograms.ResultsIn total, univariate and multivariable analysis indicated that age, International Classification of Diseases for Oncology, historical stage, primary site, surgery information, radiotherapy, and chemotherapy were independent prognostic variables for overall survival or cause-specific survival. Nomograms based on the multivariable models were built to predict survival, and we achieved a higher C-index in subsequent multidimensional validation.ConclusionsAge, historical stage, and chemotherapy were independent prognostic variables for overall survival and cause-specific survival of MGCTB patients, and radiotherapy and primary site were independent prognostic variables for overall survival. Nomograms based on significant clinicopathological features and clinical experience can be effective in predicting the probability of survival for MGCTB patients.

Prognostic utility of serum YKL-40 in patients with cervical cancer

Inflammation is one of the hallmarks of cancer and plays a crucial role in the development and progression. The objective of the present study was to investigate if high serum YKL-40 is related to poor prognosis in cervical cancer (CC) patients. A prospective biomarker study of 116 patients with CC (FIGO stage Ia: n = 4; Ib: n = 55; II: n = 26; III: n = 26; IV: n = 5) and 152 patients with cervical intraepithelial neoplasia (CIN). The patients received primary surgery, radiotherapy and chemotherapy according to standard guidelines during the period 2001–2004. Seventy patients died during the follow-up period (median 117 months, range 104–131). Serum concentrations of YKL-40 were measured by ELISA. Serum concentrations of YKL-40 were increased (p < .001) in CC patients (median 76 µg/L, IQR 45–148) compared to CIN patients (44 µg/L, IQR 30–61) and healthy women (41 µg/L, IQR 29–58). YKL-40 was elevated (>age-corrected 95th percentile of YKL-40 in healthy women) in 30 (26%) of the CC patients. Univariate Cox analysis demonstrated that YKL-40 (included as a log-transformed continuous variable (base 2)) was associated with recurrence-free survival (RFS) (HR = 1.48, 95% CI: 1.11–1.98, p = .008) and overall survival (OS) (HR = 1.74, 1.44–2.10, p < .0001). Multivariate Cox analysis showed that stage (II + III vs. I: HR = 2.92, 1.37–6.20, p = .005), YKL-40 (HR = 1.35, 1.06–1.73, p = .018) and age (HR = 1.56, 1.21–1.99, p = .0005) were independent prognostic variables of OS. During treatment, a 2-fold increase in YKL-40 compared to baseline level was associated with short RFS (HR = 1.87, 1.27–2.77, p = .0016) and OS (HR = 1.78, 1.26–2.50, p = .0010). Serum YKL-40 is an independent biomarker of OS in patients with cervical cancer.

Prognostic nomograms based on immune scores for head-neck squamous cell carcinoma patients.

We aim to develop an immune-score nomograms for predicting overall survival (OS) of patients with HNSCC and assess the association of immune scores with prognosis. The data of 530 patients used in this study were retrieved from The Cancer Genome Atlas database. The optimization cut-point for immune scores was expressed by X-tile 3.6.1 tool. Possible prognostic factors from univariate Cox analysis were further included in a multivariate Cox proportional hazards analysis to obtain significant risk factors. Prognostic nomograms were constructed based on the factors of significant multivariate prognostic using R version 3.5.1. A calibration map was generated by comparing the nomogram prediction probability and the observation for the 3-year and 5-year OS rates. We retrospectively analyzed 462 patients downloaded from TCGA dataset. Prognostic nomograms was integrated following risk factors of significant multivariate prognostic, such as age, angiolymphaic invasion (AI), perineura invasion(Per_invasion),tumor site, immune score, tumor-node-metastasis(TNM) stage. The concordance Index (C-index) for OS predictions was 0.723 (95% CI 0.671-0.785). Moreover, we compared the powerful efficiency of the nomograms with that of the TNM staging system. OS prediction determined on immune score set compared with the TNM staging with C-index = 0.723 vs 0.612. The calibration curves for the probability of OS of 3-year or 5-year showed no deviations between the prediction by nomograms and actual reference line. The present study indicate that high and intermediate immune scores are as independent prognostic variables for OS of head-neck squamous cell carcinoma patients. We constructed novel nomograms may has the potential to provide individualized survival risk assessments and guide treatment decisions.

Expression of PD-1/PD-L1 in head and neck squamous cell carcinoma and its clinical significance.

To investigate the role of programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and P16 in patients with head and neck squamous cell carcinoma (HNSCC). A total of 95 paraffin-embedded samples of tumorous tissue of HNSCC were collected. Expression levels of PD-1, PD-L1, and P16 were determined by immunohistochemistry. A significantly higher proportion of PD-1 among patients infected with the human papillomavirus was found. PD-L1 expression is closely associated with the primary site of the tumor, postoperative recurrence, survival, PD-1 expression and P16 expression. Univariable analysis indicated that T stage, N stage, tumor node metastasis stage, tumor differentiation, and PD-L1 expression were all shown to be prognostic variables for overall survival in patients with HNSCC. In the multivariate analysis, only N stage (P = 0.010) and PD-L1 expression (P = 0.001) were found to be independent prognostic variables for overall survival. In addition, for disease recurrence, multivariate analysis showed that only PD-L1 expression was the associated independent risk factor. For the patients with negative PD-L1 expression, Kaplan-Meier analysis revealed that they had significantly worse outcomes in terms of overall survival (P = 0.001). Similarly, compared with the patients with positive PD-L1 expression, those with negative PD-L1 expression had a higher probability of recurrence (P = 0.026). The expression of PD-L1, PD-1, and P16 in HNSCC is significantly correlated. Human papillomavirus infection (P16 positive) is negatively related to postoperative recurrence. HNSCC patients with positive PD-L1/PD-1 expression tend to have better overall survival outcomes and lower probability of recurrence, providing more evidence for the PD-l-targeted immunotherapy of HNSCC.

International prognostic scoring system for mastocytosis (IPSM): a retrospective cohort study

The WHO classification separates mastocytosis into distinct variants, but prognostication remains a clinical challenge. The aim of this study was to improve prognostication for patients with mastocytosis. We analysed data of the registry of the European Competence Network on Mastocytosis including 1639 patients (age 17-90 years) diagnosed with mastocytosis according to WHO criteria between Jan 12, 1978, and March 16, 2017. Univariate and multivariate analyses with Cox regression were applied to identify prognostic variables predicting survival outcomes and to establish a prognostic score. We validated this International Prognostic Scoring System in Mastocytosis (IPSM) with data of 462 patients (age 17-79 years) from the Spanish network Red Española de Mastocitosis diagnosed between Jan 22, 1998, and Nov 2, 2017. The prognostic value of the WHO classification was confirmed in our study (p<0·0001). For patients with non-advanced mastocytosis (n=1380), we identified age 60 years or older (HR 10·75, 95% CI 5·68-20·32) and a concentration of alkaline phosphatase 100 U/L or higher (2·91, 1·60-5·30) as additional independent prognostic variables for overall survival. The resulting scoring system divided patients with non-advanced mastocytosis into three groups: low (no risk factors), intermediate 1 (one risk factor), and intermediate 2 (two risk factors). Overall survival and progression-free survival differed significantly among these groups (p<0·0001). In patients with advanced mastocytosis (n=259), age 60 years or older (HR 2·14, 95% CI 1·42-3·22), a concentration of tryptase 125 ng/mL or higher (1·81, 1·20-2·75), a leukocyte count of 16 × 109 per L or higher (1·88, 1·27-2·79), haemoglobin of 11 g/dL or lower (1·71, 1·13-2·57), a platelet count of 100 × 109 per L or lower (1·63, 1·13-2·34), and skin involvement (0·46, 0·30-0·69) were prognostic variables. Based on these variables, a separate score for advanced mastocytosis with four risk categories was established, with significantly different outcomes for overall survival and progression-free survival (p<0·0001). The prognostic value of both scores was confirmed in 413 patients with non-advanced disease and 49 with advanced mastocytosis from the validation cohort. The IPSM scores for patients with non-advanced and advanced mastocytosis can be used to predict survival outcomes and guide treatment decisions. However, the predictive value of the IPSM needs to be confirmed in forthcoming trials. Austrian Science Fund, Deutsche Forschungsgemeinschaft, Koeln Fortune Program, Charles and Ann Johnson Foundation, Instituto de Salud Carlos III, Fondos FEDER, Research-Foundation Flanders/Fonds Wetenschappelijk Onderzoek, Clinical Research-Fund of the University Hospitals Leuven, and Research-Foundation Flanders/Fonds Wetenschappelijk Onderzoek.

Decreased expression levels of ELOVL6 indicate poor prognosis in hepatocellular carcinoma.

The present study aimed to investigate the expression of elongation of very long-chain fatty acids family member 6 (ELOVL6) in hepatocellular carcinoma (HCC) tissues, and to determine its role in the development of HCC. A total of 377 HCC specimens were collected for tissue microarray and immunohistochemistry analyses. The ELOVL6 IHC score for HCC tissues was 0.97±0.71, which was significantly lower than that of the matched adjacent normal tissues (1.32±0.68; P<0.001). Patients with low levels of ELOVL6 expression were older (P=0.014) and possessed larger sized tumors (P=0.039) than patients with high expression levels. Additionally, Kaplan-Meier analysis revealed that patients with low ELOVL6 expression levels also had significantly poorer overall (P<0.001) and disease-free (P=0.029) survival times, and a greater probability of recurrence. The tumor size, tumor-node-metastasis (TNM) stage, vascular invasion and ELOVL6 expression were all shown to be prognostic variables for overall survival in patients with HCC. Multivariate analysis revealed that vascular invasion (P<0.001), TNM stage (P<0.001) and ELOVL6 expression (P=0.001) were independent prognostic variables for overall survival. In addition, vascular invasion (P=0.032) and ELOVL6 expression (P=0.041) were independent risk factors for disease-free survival, and vascular invasion (P=0.019) and ELOVL6 expression (P=0.045) were independent risk factors associated with HCC recurrence. The present study revealed that in patients with HCC, ELOVL6 expression level was reduced in HCC tissues, and that higher ELOVL6 expression levels correlated with longer survival times. This indicates that ELOVL6 may serves as an independent marker of poor patient outcome.

Analysis of prognostic factors and therapeutic patterns of recurrent stage Ⅰb-Ⅱa cervical squamous carcinoma treated with radical hysterectomy

Objective: To analyze the prognosis and appropriate treatment modalities of the patients with recurrence of early stage (Ⅰb-Ⅱa) cervical squamous cancer primarily treated with radical hysterectomy. Methods: This retrospective study included patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰb and Ⅱa recurrent cervical squamous cancer who underwent radical hysterectomy primarily from January 2007 to July 2015. Kaplan-Meier method and Cox regression analysis were performed to analyze related prognostic factors of overall survival and progression-free survival, which included age, postoperative therapy, the site of recurrence, therapy-free interval (TFI) and treatment modality. The patients who were treated with palliative chemotherapy after recurrence were selected as a subgroup. The responses of palliative chemotherapy were evaluated and analyzed among different factors, included TFI, the site of recurrence and chemotherapy regime. Results: Of the 2 071 patients, 116 relapsed Ⅰb-Ⅱa cervical squamous cancer were included in the study with the average age of (45.6±7.2) years old. 3-year progression-free survival rate and 3-year overall survival rate after recurrence were 30.2% and 42.2%, respectively. Univariate analysis implied that postoperative radiotherapy, recurrence site, TFI and treatment modality were associated with progression-free survival (P<0.05), while postoperative radiotherapy, TFI and treatment modality with overall survival (P<0.05). Multivariate analysis showed that TFI and treatment modality were independent prognostic factors for progression-free survival (P<0.05), while postoperative radiotherapy at initial treatment, TFI and treatment modality were independent prognostic variables for overall survival (P<0.05). In the analysis of treatment modality, 3-year progression-free survival rate and 3-year overall survival rate of 47 patients who were treated with definitive local therapy were significantly higher than that of 69 patients who were treated with palliative chemotherapy (P<0.01). In the subgroup analysis of palliative chemotherapy, 15 patients achieved complete response (21.7%) and 16 displayed partial response (23.2%). The overall response rate (ORR) was 44.9%. TFI (P<0.01) and chemotherapy regime (P<0.05) were significant factors associated with ORR. The ORR of TFI ≥12 months was significantly higher than that of TFI <12 months. Besides, the ORR of paclitaxel plus platinum chemotherapy was prominently higher than that of other regimens, while there was no significant difference between the ORR of paclitaxel plus cisplatin and other platinum (P=0.408). Conclusions: For recurrent stageⅠb-Ⅱa cervical squamous carcinoma treated with radical hysterectomy, use of definitive local therapy for suitable patients is advised to achieve better prognosis. In terms of palliative chemotherapy, longer TFI may mean better ORR and the combination of paclitaxel plus platinum is preferred.

Mitofusin-2 acts as biomarker for predicting poor prognosis in hepatitis B virus related hepatocellular carcinoma

ObjectiveTo investigate the expression of Mitofusin-2 (MFN2) in HCC tissues and its role in the development of HCC.MethodsA total of 107 HCC specimens were collected for tissue microarray analysis and immunohistochemistry (IHC) analysis. The relationship between MFN2 expression and clinical features of patients with HCC was analyzed.ResultsExpression level of MFN2 in HCC tissues was 0.92 ± 0.78, significantly lower than that of matched paracancerous liver tissues (1.25 ± 0.75). Patients with low expression of MFN2 had significantly higher rates of cirrhosis than those with high expression of MFN2 (P = 0.049). Kaplan-Meier survival analysis showed that HCC patients with low expression of MFN2 had a worse prognosis in overall survival than HCC patients with high expression of MFN2 (P = 0.027). Patients with high expression of MFN2 had a better prognosis in disease-free survival compared with HCC patients with low expression of MFN2 (P = 0.047). Vascular invasion and MFN2 expression were shown to be prognostic variables for overall survival in patients with HCC. Multivariate analysis showed that vascular invasion (P < 0.001) and MFN2 expression (P = 0.045) were independent prognostic factors for overall survival. Vascular invasion (P < 0.001) and MFN2 expression (P = 0.042) were independent risk factors associated with disease-free survival.ConclusionOur data revealed that MFN2 expression was decreased in HCC samples. High MFN2 expression was correlated with longer survival times in patients with HCC and served as an independent factor for better outcomes. Our study therefore provides a promising biomarker for the prognostic prediction of HCC and a potential therapeutic target for the disease.